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Monday, 11 April 2016

Most Common Disease of 50plus: The Clinical trials and Studies of Polymyalagia Arthritis (Rheumatica), a Common form of Musculo-Skeletal disorders(MSDs)

Kyle J. Norton (Scholar)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
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Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Musculoskeletal disorders (MSDs) are  medical condition mostly caused by work related occupations and working environment, affecting patients’ muscles, joints, tendons, ligaments and nerves and developing over time. A community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home. Musculoskeletal pain was reported by 57% of those interviewed(1).

      Types of Musculo-Skeletal disorders in elder(2)

1. Osteoarthritis
2. Gout
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
6. Osteoporosis
7. Low back pain
8. Fibromyalgia



                       

                  Polymyalagia Arthritis (Rheumatica)


Polymalagia Arthritis is defined as a condition a common inflammatory rheumatic disease which causes pain, stiffness and tenderness in large muscles, including muscles shoulders and pelvic girdle as a result of the presence of a synovitis in proximal joints and periarticular structures.

                         The Symptoms 

1.  Dr. Kennedy-Malone LM, and Dr. Enevold GL. at the University of North Carolina School of Nursing in Greensbor, showed that Polymyalgia rheumatica (PMR) is a rheumatic condition with pain and stiffness, primarily in the neck, shoulders, hips, and pelvic girdle.(3).  The prevalence of polymyalgia rheumatica is approximately 16.8 to 53.7 per 100,000 of the population >50 years of age(5)

2.  Hôpital Ballangerstudy in differentiation of crowned dens syndrome were misdiagnosed as polymyalgia rheumatica, giant cell arteritis, meningitis or spondylitis suggested that symptoms of PRA may also include fever, cervical stiffness, headaches and biological inflammatory syndrome(4).

3. Low back pain
Low back pain in patient with Polymalagia Rheumatica may be resulted of affecting predominantly extra-articular synovial structures, causing inflammation of lumbar bursae(5).

4. According to Eleonora Reicher Rheumatology Institute, Warszawa, Poland, Patients with RA may present with symptoms of malaise, fatigue, weight loss and other features suggesting inflammation(5).

5. Dr. Lim SH and Dr. McLeay G. also expressed concerns of the prevalence of PMR with symptoms and signs are often nonspecific in elderly as the syndrome pain and stiffness in the proximal muscles, anorexia, fatigue, depression, weight loss, fever and temporal headache(6).

6. Other symptoms have also been found to associate to patient with PMA including sleep disturbance. anxiety, and depression, according to the joint study lead by the University of Leeds(7).

7. The disease is also found to be influential to patient poor functional impact; impact on daily schedule(8) as a result of "overwhelming" symptoms, in prevented them carrying out "fundamental activities" and "generally living life"(8).


                            The causes and Risk factors

The cause of PMR is not well understood, but researchers believe it is a result of the abnormal inflammatory activity of inflammatory cells and proteins of the immune system due to the presence of a synovitis in proximal joints and periarticular structures, causes by the following

1. Influenza B infection
Number of infectious agents have been found to induce the cause of polymyalagia rheumatica(PMR) associated to human leukocyte antigens (HLAs), such as HLA-DRB1 and HLA-DQB(10). According to the Kobe University Hospital, contracting influenza virus B is also found to influence to the development of PMR(9). Dr. Peris P said," Onset of symptoms in PMR is unrelated to seasonal pattern. Yet almost 50% of cases occurred in the months of May, February, and August"(12) and there is no association between infection and onset of polymyalgia rheumatica(13), the Ciudad Sanitaria y Universitaria de Bellvitge argued.

2. Genetic factors
In the study to evaluate HLA-DRB1 associations in patients with polymyalgi arheumatica (PMR), acording to the study based HLA-DRB1 genotyping in 89 PMR patients, 44 GCA patients, and 99 unrelated healthy controls from the same geographic area(10). Dr Pease CT and the research team at the University of Leeds, in the diagnosed of musculoskeletal disorder said, "the presence of HLA-DRB1*04 may indicate underlying RA or TA."(11)

3. Environmental factors
Environmental contagious factors have been found to link to the onset of at least 1/4 percent of the patient with PMR, according to the study of 460 patients (128 with isolated PMR, 227 with isolated GCA, 105 with PMR/CGA), by the Dupuytren University Hospital, Limoges(14).
According to the database of the World Health Organisation (WHO), statin, the prescribed medication for lowering blood cholesterol levels, using Anatomical Therapeutic Chemical (ATC) classification, may be may be associated with the occurrence of PMR(15).
Some researchers including Goëb V also concerned the risk of  Cerivastatin-induced PMR(16) and patient reexposure to a statin is also associated to the developed polymyalgia rheumatica(17)


B.2. Risk factors
1. Gene
Patient carrying gene of rs20541 (R130Q) polymorphism in the IL-13 gene is showed to have an increased risk of Polymyalgia Rheumatica(PMR)(18). In elder, genetic abnomality of IL1RN polymorphism is also an risk factor for the disease but not associated to PMR severity(19), according Universidad de Cantabria. The influence of persistence high levels of interleukin 6 (IL-6)(Proinflammatory cytokines) also elevated the risk of PMR (20).

2. Aging
If you are over 50 years of age, you are at increased risk of Polymalagia Arthritis (PMR)(21), as a result of age-related chronic inflammatory conditions in increased effector functions of phagocytes, chemotaxis, phagocytosis, and oxidative burst as well as reduced immunity(22).  In support to the above, the Slovak Academy of Sciences study suggested that patient with Polymyalgia Rheumatica(PMR) are found to have low levels of cortisol, during ongoing inflammation, decreased levels of adrenal androgens which is an expression in aging population(23)

3. Diet
Diet plays an important in reduced and increased risk of PMR, depending to specific dietary components. Intake of red meat and certain dietary components have shown to predict the onset of Polymyalgia Rheumatica(PMR) depending to influential risk from other lifestyle causes(24).

4. Geographical and temporal differences
People who live in ceratain Geographical and temporal areas are susceptible to increased risk of Polymyalgia Rheumatica(PMR). Dr Cimmino MA and Zaccaria A said," Epidemiological studies have helped to unravel the etiopathogenic factors at work in PMR/GCA,... the incidence of PMR varies between 12.7/100,000 in Italy and 112.6/100,000 in Norway"(25).

5. Smoking
One of most additive form of human life style of thousands of year has found to causes many types of deathly cancer and viarity of chronic inflammatory diseases, including Polymyalgia Rheumatica(PMR)(25). According to the Kameda Medical Center, reviewed of review of patients with RS3PE and PMR treated in a community-based hospital between January 2000 and December 2009, smiking is the leading causes of PMR with the effective rate of 39%(26).
Dr. Harrison BJ and the research team at the University of Manchester, insisted that Cigarette smoking is known to increase rheumatoid factor (RF) and nodule formation in patients with rheumatoid arthritis (RA) and the early inflammatory polyarthritis (28).

6. Gender
According to the review of records of 163 cases of PMR and/or TA diagnosed over a 15 year period,
if you are women, you are at increased risk to develop Polymalagia Arthritis with severity of inflammatory response(29). Dr. Dejaco C, the leading researcher at the jopint study said,"Among prognostic factors, female sex, high erythrocyte sedimentation rate (ESR) and peripheral arthritis were associated in some studies with a higher relapse risk"(30).

5. Race
Polymyalgia Rheumatica(PMR) is one of most  common rheumatic diseases in  Asian popilation specially in China and Singapore, according to Singapore General Hospital(31) and Community Oriented Program for Control of Rheumatic Diseases (32) but The prevalence of rheumatic complaints varied with the locality surveyed(32)

Some researchers also suggested that increased levels of Procalcitonin (PCT) as an early marker of bacterial infection in patients diagnosed during the 2002-06 period randomly selected.may be correlated with inflammation status of the early onset of PMR as well as sun exposure, and nulliparity(27).



                                           The Complications

Patient with Polymyalgia Rheumatica(PMR) are limited to number daily physical functions and daily physical activities in most cases, according to Keele University and Mayo Clinic, the primary complications of PMR patients aref pain, stiffness and functioning(33)(34). Other more prevalence of complications of Polymyalgia Rheumatica(PMR) may include

1. Visual loss
Due to the nature of an inflammatory vasculopathy that involves large- and medium-sized arteries, patient with Polymyalgia Rheumatica(PMR) are associated to the complication of visual loss, according to the study by Dr. Schmidt J and Dr. Warrington KJ.(35). Dr.Hart FD. in the study of Visual complications of polymyalgia rheumatica (polymyalgia arteritica) siad," patients with polymyalgia rheumatica (polymyalgia arteritic) developed evidence of cranial arteritis (in one case two years and in one six months) following withdrawal of steroid therapy after apparent cure"(36).

2. Stroke
Polymyalgia rheumatica (PMR), a relatively common rheumatic disease, particularly in the elderly effecting the medium and large arteries causes of stroke(35). According to Taipei Medical University, PMR was associated with a significantly higher risk of stroke in the three-year follow-up period, in a study included 781 patients with PMR from the Taiwan Longitudinal Health Insurance Database between 2001 and 2005(37).
Dr. Narváez J and the research team at the Hospitalet de Llobregat said,"Patients with GCA presenting with apparently isolated PMR have a significant risk of developing transient or permanent disease-related ischemic complications; these complications occurred in 50% of the cases"(38).

3. Low back pain 
Interspinous bursitis associated with lower back pain, a frequent finding in the lumbar spine of patients with PMR may be as a result of Inflammation of lumbar bursae, according to Istituto di Ricovero e Cura a Carattere Scientifico in the finding by using magnetic resonance imaging (MRI)(39). The joint study lead by the University of Cantabri said,"The most common clinical manifestations at diagnosis were: PMR features, often with atypical clinical presentation (n=23 patients, 72%); diffuse lower limb pain (n=16 patients, 50%); constitutional symptoms (n=12 patients, 37%), inflammatory low back pain (n=9 patients, 28%) and fever (n=7 patients, 22%)(40).

4. Cervical interspinous bursitis
Cervical interspinous bursitis, an active inflammatory involvement of cervical bursae is likely to cause discomfort in the neck of patients(41) and also a frequent finding in the lumbar spine of patients with PMR(42). Although it is not associated with clinical symptoms, it has been found to associate to the spinal pain reported by the patients(42).

5. Renal failure
Patient with Polymyalgia rheumatica (PMR) may be important of monitoring renal function due to renel failure is found to associate to a few cases of AA amyloidosis(43), the King's College Hospital NHS Foundation Trust suggested.
According to the reports of Hospital Universitario 12 de Octubre, "two patients with PMR (one with associated GCA) who developed nephrotic syndrome and end-stage renal failure caused by massive amyloid deposition"(44)

6. Perforated colonic diverticular disease
The association of Polymyalgia Rheumatica(PMR) and perforated colonic diverticular disease may be result of proinflammatory expression and high incidence of other co-morbidities including colonic pathology(45), according to the joint study lead by the James Paget University Hospital.

7. Cancers
The investigation of a total of 185 patients with polymyalgia rheumatica (PMR) and temporal arteritis (TA) diagnosed during 1978-83 and their 925 matched controls with the data files at the Cancer Registry of Norway at the end of 1987, indicated that the malignancy of cancer are found to associate with 24% in patient with PMR(46).
Dr. Ji J and the research team at the Lund University said," Patients hospitalized for PMR and GCA had a marginally increased risk of cancer, with the highest risk noted for the first year after hospitalization. However, for specific cancers, such as skin cancer and leukaemia, the increases were still significant for patients diagnosed later than 1 year after hospitalization"(47).


    Diseases associated with Polymyalgia Rheumatica(PMR)


1. Giant cell arteritis
 Giant cell arteritis shares many similarities with Polymyalgia rheumatica, according to the statistics
Patient with  Giant cell arteritis is associated to 50% higher risk of  polymyalgia rheumatica. On the other hand, there are 20% risk of development of Giant cell arteritis in patient polymyalgia, rheumatica. But the clinical manifestations, the relationship between GCA and PMR is not yet clearly established(48).
Medication and therapies used for treatment of polymyalgia rheumatica are also found effectively for giant cell arteritis as well, including Corticosteroids and anti-interleukin-6 receptor therapy(50).

2. Autoimmune thyroid disease and thyroid diseases
Autoimmune thyroid disease is defined as a condition in which the immune system wrongly viewed the thyroid gland and hormones produced as a foreign substances, thereby, producing antibodies to destroy them.  In a study of 250 patients with autoimmune thyroid disease, seven (2.8%) were found to have polymyalgia rheumatica. Female patient with age over 60 are found to have an increased risk of over 9.3% (49). Autoimmune thyroiditis is often related to Rheumatoid Arthritis due to other non-specific autoimmune organ diseases(51)
But according to the Service de Médecine Interne B, there is no evidences in support that the giant cell arteritis or polymyalgia rheumatica patients are at increased risk for hypothyroidism or hyperthyroidism(52)

3. Stroke
Besides cancer and heart diseases, stroke is the third leading cause of death. Approximate 1/4 of all stroke victims die as a direct result of the stroke or it's complications. The study of a total of 781 patients with PMR from the Taiwan Longitudinal Health Insurance Database between 2001 and 2005, patients with PMR are associated to an increased of stroke in comparison to controls(53).
Dr,.Hernández-Rodríguez J and the research team at the University of Barcelona suggested that Patients with GCA with apparently isolated PMR have a significant risk of developing ischemic complication(54).

4. Gastroesophageal reflux disease (GERD)

The prevalence of upper gastrointestinal (GI) diseases is increasing in subjects aged 65 years and over. Pathophysiological changes in esophageal functions that occur with aging may, at least in part, be responsible for the high prevalence of the disease. Use of medication of proton pump inhibitors (PPIs) are found to reduced risk of GERD in patient with polymyalgia rheumatica(55) in comparison to those without.

5. Vasculitis
Vasculitis is diseases associated to the inflammation of blood vessels. Patient with Polymyalgia Rheumatica(PMR) may present together with large vessel vasculitis (LVV) as a result of the inflammatory impact(56). Tocilizumab showed to improve symptoms of disease and inhibit inflammatory markers(57).Methotrexate effectively reduces relapse rate and lowers the cumulative dose of glucocorticoid therapy in patient with Polymyalgia Rheumatica(PMR)(58).

6. Peripheral vascular disease
Patient with Polymyalgia rheumatica, the most common inflammatory rheumatologic conditions in older adults are associated with an excess risk of vascular disease in comparison to the onset of vascular event in patients with and without polymyalgia rheumatica(59). Dr. Warrington KJ and the research team at the Mayo Clinic, Rochester said. "Patients with PMR appear to have an increased risk of PAD" in an inception cohort of all Olmsted County, Minnesota residents diagnosed with PMR between 1 January 1970 and 31 December 1999(60).

7. Renal function impairment 
Renal function impairment may associate rarely to patient with Polymyalgia Rheumatica(PMR). Only a few cases of AA amyloidosis secondary to PMR have been described in the literary data bases,according to the King's College Hospital NHS Foundation Trust(61). Dr. Escribá A and the research team at the Hospital Universitario 12 de Octubre, also expressed concerns of several cases of systemic amyloidosis associated with polymyalgia rheumatica (PMR) caused by massive amyloid deposition(62).


               The Complications

The Most common complications for people with Polymyalgia Rheumatica(PMR)
1. Ischemic complications
Patient with Polymyalgia Rheumatica(PMR) are found to have an lower risk of developing ischemic events, according to University of Barcelona(63). Dr. Narváez J and the research team at the joint study lead by Hospital Universitario de Bellvitge-IDIBELL said," Patients with GCA presenting with apparently isolated PMR have a significant risk of developing transient or permanent disease-related ischemic complications" and "these complications occurred in 50% of the cases"(64). Some patient of PMR with thrombocytosis also are found to at greatest risk for the development of stroke as well(65).

2. Vascular events
DR. Staud R. said," Patients with polymyalgia rheumatica had a 2.6-fold increased risk for vascular events at a median 7.8 y"(66). Youngest age groups patient with Polymyalgia Rheumatica(PMR) are associated to the greatest risk of vascular events in comparison to other age group(67).

3. Interspinous bursitis
Interspinous bursitis, a frequent finding in the lumbar spine of patients with PMR is found to have a potential cause of spinal symptoms probably due to the presence of cervical and lumbar bursitis(68). Other study suggested that the complications of low back pain reported by patients with PMR may also be result of Inflammation of lumbar bursae, the Istituto di Ricovero e Cura a Carattere Scientifico study suggested(69).

4. Shoulder inflammation

Shoulder inflammation is found common in 50%patient with PMR(70). But according to the research lead by Dr. Curran JF , shoulder arthritis may be result of inflammatory, degenerative, and septic arthritis and rarely the initial joint involved in rheumatoid arthritis and generally the symptoms is respond to the basic management for rheumatoid arthritis(71).
5. Stress fractures
One of the complication of rheumatic disease, including Polymyalgia Rheumatica(PMR) may often be delayed or missed in diagnosis, leading to improper treatment, the Sourasky Medical Center suggested(72). Dr. Mäenpää HM and the research team at the Rheumatism Foundation Hospital said,"a patient with rheumatic disease experiences sudden and unexplained pain localised in the forefoot, above the ankle, below the knee, or in the pelvis, a stress fracture should be suspected"(73).

6. Infection diseases
Patient with Polymyalgia Rheumatica(PMR) are found to be susceptible to the complications of infectious diseases, such as Chronic Epstein-Barr virus infection(74), Mycoplasma pneumoniae infection(75),........

                   The Diagnosis 

There is no specific test to diagnose polymyalgia rheumatica. If you are over age of 60 with some of the symptoms mentioned above without joint swelling, Joint tenderness, decreased range of motion in joints, Visible joint damage, etc., you may be already on the early onset of Polymyalgia Rheumatica(PMR)
Dr. Loeslie V said, ..." diagnosis of rheumatologic disorders in the elderly is often complicated " (due to) "clinician’s inability to differentiate among similar manifestations of rheumatologic disorders, the presence of comorbid conditions, and symptoms attributed simply to aging"(76).

1. Blood test
a. Erythrocyte sedimentation rate (ESR) is the blood test to exam the red blood cells in a test tube. he higher the ESR value is an indication of inflammation. Requisite indication of erythrocyte sedimentation rate (ESR)>40 mm/h is considered an important for the diagnosis of polymyalgia rheumatica (PMR)(78). Error reading may occur, normal erythrocyte sedimentation rate (ESR) reading has found to presence to approximately one-fifth of all PMR patients, more commonly in men(77).  A patient with PMR with an ESR lower than 40 mm/h is rare but has happened to men of that represent a clinically less severe than the classic form of PMR(78).

b. C-reactive protein (CRP)
Blood test measures the levels of C-reactive protein (CRP) produced by the liver in response to an injury or infection and people with polymyalgia rheumatic.Patient with PMR are associated to elevation of levels of both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)(79).

c. Blood test for thrombocytes
Patient with polymyalgia rheumatica have an unusually high number of thrombocytosis. On the other hand, People with anemic polymyalgia rheumatica have a lower number of red blood cells than normal. The associated of thrombocytosis acted as  an inflammation parameter to rheumatic diseases such as Rheumatic Polymyalgia is found to be correlated to disease activity(81)

d. Rheumatoid factor (RF)
RF is an antibody, a protein made by the immune system presented in the blood of people with rheumatoid arthritis, but not in the blood of people with polymyalgia rheumatica(82).

2. Biopsy
Polymyalgia rheumatica is often associated with giant cell arteritis with biopsy by taking a small sample from the scalp artery in the emporal artery and examined under a microscope in a laboratory(83). The biopsy would be helpful to rule the presence of giant cell arteritis through observation of abnormal cells in the artery walls

The Southend University Hospital diagnosed criteria of PMR include "patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain"(80).


The Misdiagnosis and delay diagnosis


Polymyalgia rheumatica (PMR) is a very painful inflammatory disease, affecting the shoulder region and the pelvic girdle region in people over 50 year of age. But according to Dr, Talke M and Dr. Schmidt WA. said" the misdiganosis is common, .....taking a structured medical history and performing a thorough clinical examination are crucial" and  "patient with elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels should be investigated particularly in patients who present with new onset bilateral shoulder pain and pronounced general impairment of movement"(84).

1. Spondyloarthropathy 
Late onset of  pondyloarthropathy, a disease characterized as a joint disease of the vertebral column is often misdiagnosed as Polymyalgia Rheumatica(PMR). According to the centre hospitalier d'Aulnay-sous-Bois, eight patients with spondyloarthropathy with with poor response to corticosteroids and multiple flares,were misdiagnosed as PMR(85). The Gaziantep University study also showed the similarities of pondyloarthropathy and PMR in a patient of 50 year of age(86).

2. Osteoarthritis of the shoulders 
Osteoarthritis of the shoulders in some case may be wrongly diagnosis as PMR due to the relapse of the symptoms of similarity in both diseases(87), According to the Istituto di Ricovero e Cura a Carattere Scientifico, patients with PMR and pain in the shoulder is alo hound in 2 patients with spinal osteoarthritis(88).

3. Calcifying tendinitis of the rotator cuff
Calcifying tendinitis is disease characterized by a building-up of calcium in the rotator cuff (calcific deposit) in some case may be misdianosed as PMR(87).

4. Bursitis
Bursitis is an inflammation of a bursa of the knee, elbow or shoulder in some cases may be misdiagnosed as PMR(87). According to Asklepios Clinic, in the investigation of 54 consecutive patients with recent-onset PMR, over 30% with Subdeltoid bursitis(89).

5. Rheumatoid arthritis

Rheumatoid arthritis, a chronic inflammatory rheumatic diseases, found most often in the people age of 50 and over may be misdiagnosed as PMR(87). According to the Università di Pavia, the percentage of patient diagnosed with RA and PMR often change in first and during follow up diagnosis(90) due to like onset of patient with PMR.


                The Prevention and management 

The Do and do not’s list
What to avoid may be the first question of people who are age of 50 and over and concern that they may be in stage of developing the disease. Other people may want to know what they can do to protect themselves against the early onset.

1. Reduce intake of saturated and trans fat and increase intake of omega 3 fatty acids
Although Limited studies have shown that certain dietary fatty acids (ie, oleic acid and alpha-linolenic acid) reduce biomarkers of inflammation(91).
Dr. Li Z and the research team at the Jilin University showed that ω3-polyunsaturated fatty acids (ω3-PUFAs) not only have beneficial effects on cardiovascular function but also promoted the docosahexaenoic acid (DHA) in reduced inflammation(93).
 The results of over 13 double-blind, placebo-controlled studies involving a total of more than 500 people suggest that omega-3 fatty acids may improve symptoms of rheumatoid arthritis. One of the ways it appears to work is by decreasing the production of inflammatory chemicals(94). 

2. Increasing the ratio of (n-3) : (n-6) PUFA
 The industrial elocution induced Western style diet in over consumption of ω6 polyunsaturated fatty acids (PUFA) over many decades  has been found to distort the ratio of ω3:ω6 fatty acids, one of the leading cause of chronic inflammatory diseases, including Polymyalgia Rheumatica(PMR)(92).
 Increased ratio of (n-6) : (n-3) PUFA are found to promote chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer’s disease (AD)(95).

3. Increase intake of fruit and vegetable
Consumption of fruit and vegetable is found to associate in reduced the over expression of inflammation and oxidative stress of that have found to induced chronic inflammatory diseases risk of stroke, coronary heart disease, etc,...(96)
A cross-sectional study of ≈1200 Puerto Rican adults aged 45-75 y, we assessed FV intake with a food-frequency questionnaire, suggested, but not quantity, appears to be important in reducing inflammation(97).

3. Avoid high glycemic index diets
 High glycemic index diets with low fiber content are rich in trans fat has showed to induce over activation of the immune system, leading to excessive production of pro-inflammatory cytokines of that promoting inflammatory diseases(98).

4. Reduced intake of pro inflammatory foods, such as sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc,.... According to the study by University of Hertfordshire Over consumption of fat content, especially from saturated fat, and cholesterol and reduced the intake of whole-grain foods, fruits, and vegetables, accompanied with the high amount of sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc.  in Western diet is found to be the leading causes of metabolic syndrome(99) of which induced risk of chronic inflammatory diseases(100).

5. Increase in take of anti inflammatory foods, such as fresh vegetables and fruits, seeds and sprouts whole grain, fish, turkey, chicken, legumes, etc(98).
6. Stop smoking
Smoking are associated with 39% of risk of Polymyalgia Rheumatica(101), according to the study of 28 patients with RS3PE and 123 with pure PMR by the Kameda Medical Center.
7. Moderate exercise
Moderate exercise enhances immune function in fighting against inflammation and and reduced inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]) markers of that attenuate to risk of
Polymyalgia Rheumatica(PMR)(102).

8. Etc.


                                    The diet

Dietary consumption plays an important part in reduce or increase risk of chronic inflammatory diseases. A typical American diet with high amount of red meat, fat and trans fat, processed, meat, artificial ingredients, refined products are associated to promote the expression of pro inflammatory cytokines, leading to all kinds of diseases including chronic inflammatory, cardiovascular diseases and diabetes.

1. Organic Soy
Dietary rich in organic soy gas been found to associate to decreased risk of chronic inflammatory diseases through attenuation of inflammatory marker such as C-reactive protein (CRP) of which related to risk of Polymyalgia Rheumatica(PMR)(103).
Dr. Nasca MM and the the research team at the Beth Israel Deaconess Medical Center suggested, Soy nuts were associated with a trend toward reduction in C-reactive protein in normotensive women, improved over all inflammatory process(104).

2. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Green tea polyphenols (GTP) has an effectiveness against chronic inflammation through attenuating the deterioration of bone microarchitecture, according to the Texas Tech University Health Sciences Center, in animal study(105).
Also in rat study, alcoholic extracts of green tea (AE) exhibited its analgesic and anti-inflammatory properties, through inhibited carrageenan-induced cell migration(106).
Decaffeinated dreen tea also expressed the  immunomodulatory effects through enhanceing the immune system against inflammatory disease in rainbow trout(107).

3. Olive oil
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
Consumption of extra virgin olive oil (EVOO) has been found to decrease joint edema, cell migration, cartilage degradation and bone erosion throguh attenuate the levels of proinflammatory cytokines and prostaglandin E2(108). according jopint study by the University of Seville.
In adult male Balb/C mice study, olive oil decreased the second phase of formalin-induced pain through its antinociceptive and anti-inflammatory activity(109).
The Chemistry and health of olive oil phenolics study also found, the positive effects of olive oil phenolics on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, etc,.....(110).

4. Salmon
Salmon with rich in Omega 3 fatty acids is necessary to reduce risk of expressionless of markers of inflammation to attenuate the inflammatory response of the immune system, according to the study by the Tufts University(111).
High saturated fat diets with low omega 3 fatty acid intake increased omega-6:EPA+DHA ratio diets causing some measures of inflammation(112).

5. Circuit fruits
Circuit fruit contain high amount of Quercetin which can reduce the risk of chronic inflammatory diseases as a result of anti inflammatory(113) and antioxidant effects(114).



                       The Phytochemicals 

Significantly inflammation has been found to accompany with patient with Polymyalgia Rheumatica(PMR). Certain phytochemicals have found effectively for treatment of  inflammatory symptoms of patient with PMR, including the following

1. Polyphenols(-)-epigallocatechin-3-gallate (EGCG)(Green tea)
Polyphenols(-)-epigallocatechin-3-gallate (EGCG) has showed to process anti viral and bacterial effects through immune expression such as chronic or acute inflammation(115). Dr. Xiao J and the research team at the Shenzhen Institute of Advanced Technology suggested, pure extract of (-) epigallocatechin gallate (EGCG) inhibited inflammatory effects through its antioxidant activities against oxidative stress and down regulated pro-inflammatory markers(116).
According to the Universitat de Girona (UdG), Polyphenols(-)-epigallocatechin-3-gallate (EGCG) also showed to reduce pain in attenuate the alterations by diminishing apoptotic gene overexpression in skeletal muscles(117)

2. Curcumin
Curcumin, a phytochemical found in turmeric used in the Indian cooking recipe has found to process the antioxidants and anti inflammatory effects, epidemiologically.
The phytochemical also showed to inhibited muscle pain, muscle damage, inflammation and delayed onset muscle soreness, the SportsMed Canterbury study suggested.(118), through attenuate the inflammatory responses and production of reactive oxygen species (ROS) that sustain both inflammation and oxidative stress(119).
In fact Dr. Anand P and the research team at the University of Texas M.D. Anderson Cancer Center, curcumin beside inhibited pain in many therapeutic levels but also linked to suppression of inflammation; angiogenesis, tumorigenesis and diseases of the cardiovascular, pulmonary, and neurological systems(120).

3. Resveratrol
Resveratrol (RES), a well-known antioxidant and anti-inflammatorycompound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection(121). According to the University of Arizona study, resveratrol facilitated acute and chronic pain through activation of AMPK, the enzyme played a key role as a master regulator of cellular energy homeostasis(122).

4. Boswellic acid
Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. recent study showed that the acid are also responsible for inhibition of pro-inflammatory enzymes(123). Dr Bishnoi M and the research team at the University Institute of Pharmaceutical Sciences, the phytochemical also may help to reduce the therapeutic doses of conventional NSAIDs and also reduce side effects when used conjunction with nimesulide(124).

5. Cucurbitacins 
Cucurbitacins found in the common pumpkins and gourds has found to process anti-inflammatory and analgesic activity in redued pain through inhibition of the neurogenic (first phase) and inflammatory phase (second phase) of formalin-induced pain(125). The phytochemical also showed to inhibit pain caused by chronic rheumatic disease through anti pro inflammayory cytokine activity(126).

                                The Antioxidants
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge.

1. Immune system and functioning (Free radical scavengers)
Free Radicals play an important role in the function of the Immune System. The immune system produces free radicals to kill foreign microbes(176, 127)(177,128), but the production of free radical sometime can be excessive, leading to formation of a large number of free radicals(178,129)(179,130). The domino effects have shown to induce many chronic illness, such as cancers(179,130).

a. Vitamin A
vitamin A plays an essential roles in enhancing a broad range of immune processes, including white blood cells activation and proliferation(180,132)of T-helper-cell differentiation, the production of specific antibody in regulation of the immune response(182,133).

b. Vitamin C
Due to recent promotion of western diet in some developed country, deficiencies of micronutrients are emerging as the limiting factors in ensuring children's optimal health, according Bayer Consumer Care Ltd(134). Deficiency of vitamin C and zinc in fact, interfere with normal children's growth and development(134). Researchers found that vitamin C raised the concentration in the blood of total immunoglobulin(183,135) in promotion of the ability of antibodies and phagocytic cells to clear pathogens(184,136).
c. Vitamin D
Deficiency of vitamin D is found to associate to nonspecific musculoskeletal pain. According to Maccabi Healthcare Services, improvement of levels of 25OHD reduced Polymyalgia pain induced by the use of statins(131).

c. Vitamin E
According to Dr. Moriguchi S and Dr. Muraga M., vitamin E plays an essential role in enhanced immunity especially in cellular immunity with aging(137). Deficiency of vitamin E is found to induces the decreased differentiation of immature T cells associated to the increased infectious diseases and the incidence of tumors(137)

d. Zinc
Zinc, having a regulatory role in the immune system, as a antioxidant is essential mineral improved immune system by enhancing the proper function of T and B cells(188,138) which belong to a group of white blood cells known as lymphocytes, in fighting against damaging free radicals(190,139).

2. Antioxidants and inflammation
Diet included  vitamin E significantly reduce the levels of inflammation by analyzing the pro and anti-inflammatory cytokines in the blood serum(193,140).
a. Glucosamine and chondroitin
Glucosamine used for treatment of osteoporosis and prevent the degenerative collagen, has been found to consist anti-inflammatory properties through reduction of the expression of proinflammatory cytokines such as C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6(141). The supplement also exhibited a significant reduction in pain intensity at movement and resting state, according to a Russian study(142).
b DLPA (dl- phenylalanine)
DLPA, a mixture of D-Phenylalanine and L-Phenylalanine, is a nutritional supplement amino acid(196,143). Taltirelin, a thyrotropin-releasing hormone analog, showed effectively to relieve inflammatory persistent pain through iots antiallodynic action(144).

c.  Methylsulfonylmethane, also known  DMSO2 is an organosulfur compound with the formula (CH3)2SO2 showed to exhibit anti inflammatory effects in attenuated production of mitochondrial reactive oxygen species (ROS)(145).
In a randomized, double-blind, placebo-controlled trial of Fifty men and women, 40-76 years of age  MSM (3g twice a day) improved symptoms of pain and physical function during the short intervention without major adverse events, after 12 weeks(199,146)(200,147).





                                                      Treatments




A. In conventional medicine perspective
A.1. Non Medication
1. Fasting as part of a naturopathic treatment
Fasting may be formed part of polymyalgia rheumatica (PMR) treatment, according to the Dr. Stange R. and Dr, Pflugbeil C. a complex therapy with methods of natural medicine comprising fasting as its main treatment element may be the best solution for treatment of the diseases(148), as the therapy has significant improvement of the immune condition of the intestine and consequently of the whole body(149).

2. Diet therapy
Leucine-rich milk and whey proteins may be a potential treatment of age related loss of muscle mass and strength, according to the study of Douglas Paddon-Jones and Dr. Blake B. Rasmussen(150). Other in a A randomized double blind crossover trial, suggested that exercise and amino acid supplementation (AAS) together may be effective in enhancing not only muscle strength, but also combined variables of muscle mass and walking speed and of muscle mass and strength in sarcopenic women(151).


A.2. Medical treatment
1. Tocilizumab (TCZ)
1.1. The effectiveness
Tocilizumab (TCZ),the first humanized anti proinflammatory agent in the interleukin-6 receptor-
inhibiting monoclonal antibody developed to treat rheumatoid arthritis, may also be efectively for treatment of PMR(152) becauses of its significant improvement of the patient's clinical and biochemical PMR activity(152).
In the study to assess the outcomes of 10 patients with relapsing/refractory GCA, TAK, or PMR treated with tocilizumab (TCZ), found that TCZ led to clinical and serological improvement in patients with PMR, through reduced symptoms of disease activity, inflammatory markers(153).

2.2. The adverse effects are not limit to
q. Dizziness
b. Headache
c. Allergic effects, such as rash; hives; itching; difficulty breathing, etc.
d. Skin changes
e. Tiredness or weakness
f. Etc.

2. Corticosteroids [CS] and nonsteroidal antiinflammatory drugs [NSAIDs])
2.1. Corticosteroids, a drug, a common presentation in primary care, and non-selective non-steroidal anti-inflammatory drugs (sometimes also referred to as traditional NSAIDs or tNSAIDs) are the first choice of treating of Polymalagia Arthritis, but the use of CS and NSAIDs in the treatment of PMR is associated with important long-term morbidity, according to Gabriel SE, Sunku J, Salvarani C.(154).
 The total of 176 patients in whom polymyalgia rheumatica (PMR) or giant cell arteritis (GCA) diagnosed between 1968 and 1980 study, treated with corticosteroids, showed no patient suffered a serious disease complication after starting treatment. Regular follow-up enabled the minimum effective corticosteroid dose to be used. Complications of treatment were infrequent(155).

2.2. The adverse effects ate not limit to
a. Corticosteroids [CS]
a.1. Corticosteroid withdrawal syndrome
a.2. Hyperglycemia
a.3. Insulin resistance
a.4. Diabetes mellitus
a.5. Osteoporosis
a.6. Depression
a.7. Colitis
a.8. Etc.

b. Nonsteroidal antiinflammatory drugs [NSAIDs]
NSAIDs may cause large intestinal ulcers, bleeding, and perforationoccasionally(156), mostly in duodenum of which represent a range of asymptomatic pathologies but some are life threatening(156).The use of the medication are also found to induce important long-term morbidity(157).

B. In herbal  and traditional Chinese medicine perspective
B.1. Diet modification according herbal and TCM medicine specialist
1. Top foods to reduce risk of inflammation
Low-grade inflammation has found to play a pathophysiological role in patient with Polymyalgia Rheumatica(PMR), according to the University Giessen(158).According to Medical University Innsbruck, the relationship between diet, immunity, and the microbiota, may be necessary for us to rethink of the develop diet-based approaches to prevent or treat many diseases(283,159).
1. 1.Garlic
Garlic (Allium sativum) is a species in the onion genus, belongings to family Amaryllidaceae, native to central Asia, used popularly in traditional and Chinese medicine to treat common cold and flu, strengthen immunity, etc.... Recent studies also showed that garlic exhibits its anti-inflammatory effects against chronic inflammatory disease(160) through regulation of production of NO and pro-inflammatory cytokines and other mechanisms(161).

1.2. Ginger
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belongings to the family Zingiberaceae, native to Tamil, used in traditional and Chinese medicine to treat rheumatoid arthritis and osteoarthritis. Recent study showed that ginger expressed its anti inflammatory effects through its mediators within the complexity of antioxidant activity(162).
According to the joint study of the Tshwane University of Technology, ginger's phytochemicals beside expressed its effects on anti-inflammation, it also exhibited a host of biological activities, ranging from anticancer, anti-oxidant, antimicrobial, and anti-allergic to various central nervous system activities(163).

1.3. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belongings to the family Zingiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti-oxidant, anti inflammations, etc. agent. Epidemiological studies also found that the efficacy of turmeric for treatment for low grade inflammatory diseases(164) through its anti inflammatory(165), antioxidant(165) and immunmodulatory activities.

1.4. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, green tea has been cultivated for commercial purposes all over the world. Epidemiological studies suggested that green tea improved chronic inflammatory diseases through its anti proinflammatory cytokines(166) and
 its antioxidant(168), anti inflammatory(167) and immune modulatory(169) activities.

2. Cold water fish Salmon
Salmon is the common name for Salmonidae. They are anadromous, born in fresh water, migrate to the ocean, then travel thousands of miles in the deep sea cold water throughout their life cycle and within to five years returning to the exacted location where they were born to reproduce and die.

Nutrients
1. Protein
2. Omega-3 fatty acids
3. B vitamins
4. Vitamin D
5. Astaxanthin
is a potent antioxidant that stimulates the development of healthy fish nervous systems and enhances the fish's fertility and growth rate.
6. Selenium
7. Tryptophan
8. Magnesium
9. Phosphorus
10. Etc.

Use of salmon calcitonin, a hormone produced by the thyroid gland of salmon or a synthetic polypeptide of the same sequence found in salmon(360, 170) has shown to reduce PMR complications. Dr. Ryan SM and the research team at the Dublin Institute of Technology, suggested that salmon calcitonin may also portent for treatment of inflammatory arthritis through activation of the DNA expression of  of steroid-thyroid hormone-retinoid receptor and  tissue remodeling and degradation of the extracellular matrix (ECM) of  collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan(172).
A randomized controlled trial of salmon calcitonin attenuate bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica patients by reducing the incidence of vertebral fracture of 12.5%, with four fractures in the first year and one fracture in the subsequent year(171).
In Fact, salmon calcitonin has also been used to reduce pain in patient with inflammatory arthritis diseases, including patient with osteoporotic vertebral crush fractures(173) and spinal pain(174).. through its analgesic effect , a prospective double-blind, randomized, placebo-controlled clinical study insisted

3. Nuts and seeds Olive
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.

Olive Oil: Fat Content
1. Saturated fats
a. Palmitic acid
b. Stearic acid
c. Arachidic acid
d. ehenic acid
e. Myristic acid
f. Lignoceric acid
2. Unsaturated fat3. Monounsaturated fats
a. Oleic acid
b. Palmitoleic acid
3. Polyunsaturated fats
a. Linoleic acid
b. Linolenic acid

Monounsaturated fatty acids found abundantly in olive oil, may be beneficiary for reduced inflammation and induced antioxidation(362,175).
In a pilot double-blinded, randomized, clinical trial of topical virgin olive oil versus piroxicam gel in osteoarthritis of the knee, conducted by Ardabil University of Medical Science, researchers showed use of  olive oil in the experiment is more effective than medical gel for knee osteoarthritis, probably due to its phytochemiocals oleuropein and hydroxy tyroso(364,176).
Its omega-3 fatty acids component is also found to attenuate several inflammatory and degenerative diseases, through the expression of anti-inflammatory and immunomodulatory properties(177) of that may be potential effect for treatment of PMR, a low chronic inflammatory disease.
In chronic pain diseases, omega 3 fatty acids also exhibited anti analgesic property when it used either alone or in combination with morphine after acute and chronic administration in rats(178).
Dr. Ramsden CE and the research team lead by the National Institutes of Health suggested, with the biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic, omega 3 fatty acids, could have physical and/or psychological pain modulating properties(179).

B.3. The Preventive Minerals and Vitamins
Certain minerals and vitamin such as  magnesium, selenium, copper and vitamin D may be a good sources of pain reliever according to the studies(325,180). According to the randomized to four double-blinded treatments for 12 weeks by Minnesota Applied Research Center, Glucosamine sulfate (1500 mg/d), Aquamin (2400 mg/d) and Combined treatment composed of Glucosamine sulfate (1500 mg/d) have shown effectively in improvements in symptoms of pain and stiffness of osteoarthritis(315,181).
1. Magnesium
Magnesium sulfate has shown to relieve pain in patients undergoing laparoscopic cholecystectomy (LC)(182) and neuropathic pain(183).
According to Dr. Sun J and the research team lead by the Wenzhou Medical University, magnesium used alone or conjunction with ropivacaine are effectively in exhibition of postoperative analgesia in children(184).
In fact, patient with chronic inflammatory diseases are found to associate to magnesium depletion. Dr. Nielsen FH. said," Magnesium deficiency should be considered a nutrient of significant concern for health and well-being"(185).

2. Selenium
Selenium therapy have shown to associate to pain reduction, according to study by Fourth Military Medical University(186).
In chronic pancreatitis, according to the systematic review and meta-analysis was performed per PRISMA guidelines, organic selenium may be effective for treatment of chronic pain as the result of reported change in pain score(187).
According to the Universidad de Buenos Aires, patient with chronic inflammatory diseases are found to have low levels of selenium serum(188).

3. Copper
Used topical Copper-salicylate gel has shown to relief pain for patients with the hip or knee osteoarthritis with side effects of skin rashes(330,189).
Other topical Cu-Indo gel has shown effectively against joint inflammation in the MIA-treated rat model of osteoarthritis(332,190). 
Deficiency of copper is found to associate with inflammation, oxidative Stress, and metabolic variables in adults, according to the 2008 American Society for Nutrition publication(191).

4. Vitamin D
According to the study by the University of Alberta, vitamin D may have beneficial effects in specific chronic painful conditions(192)and Vitamin D deficiency has recently been linked with a range of diseases including chronic pain(193).




  
                                             Treatment

B.2. Herbal and Traditional Chinese medicine 
Herbal medicine from different cultures have been found effectively in reduced symptoms and treatment for patient with Polymyalagia Arthritis (Rheumatica), including 
B.2.1. Individual herb
1. Comfrey 
Comfrey is a perennial Plant in the genus of Symphytum, belongings to the family Boraginaceae, native to Europe,  used in herbal and traditional medicine to ease excessive bleeding or on open wounds, relief pain and swollen, treat circulation issues, reduce cholesterol, etc. According to Merck Selbstmedikation GmbH, in the searching of the literature of multiple randomized controlled trials suggested that topical comfrey treatment significantly reduce pain, inflammation and swelling of muscles and joints in degenerative arthritis, acute myalgia in the back, sprains, contusions and strains after sports injuries and accidents, also in children aged 3 or 4 and over(194)
Dr. Staiger C said, "Comfrey root extract has been used for the topical treatment of painful muscle and joint complaints. It is clinically proven to relieve pain, inflammation and swelling of muscles and joints in the case of degenerative arthritis, acute myalgia in the back, sprains"(195).
Furthermore, the Universidade Federal dos Vales do Jequitinhonha e Mucur study in the investigation of the efficacy of comfrey expressed the promising result in control the inflammatory process and to induce collagen deposition at 8% concentration(196).

2. Devil's claw
Devil's claw also known as wood spider, is a plant of genus Harpagophytum in the family of Pedaliaceae, native to South Africa.The plant has been used as herb in traditional and herbal medicine to treat fever, rheumatoid arthritis, skin, gallbladder, pancreas, stomach and kidneys conditions, etc. Because of its strongly anti inflammatory activities, the herb may be used to treat inflammatory rheumatic disease, causing pain, stiffness and tenderness in large muscles. According to University Hospital Zurich, Extracts of devil's claw inhibited a wide range of proinflammatory mediators(199) which are important in the pathophysiology of inflammatory rheumatic disease(197).
Dr. Chrubasik S said that preparations of devil's claw extract, should be taken account of the presence of the quantity of harpagoside of which has proven importantly in relived painful lower back or arthrotic pain as an attractive alternative to synthetic analgesics(198).

3. Valerian
Valerian is a perennial flowering plant, in the genus Valeriana, belongings to the family Valerianaceae, native to Europe and parts of Asia  used in traditional herbal medicine as a sedative and relaxing agent and to treat the liver, the urinary tract, the digestive tract problem, nerve conditions, etc.,...According to the University of Peshawar, Valerian expressed anti inflammatory effect on the acute and chronic phase inflammation models in male Wistar rats, on dose dependant manner(202), particular in crude extract at a dose of 200 mg/kg at all observed durations(203).
According to the University of Washington, Valerian may be used as sedative in reduced sleep(200) disturbance of patients induced fatigue(201) with inflammatory rheumatic pain(200).

4. Willow bark
A herbal medicine used over thousands of years for treatment as an anti-inflammatory, antipyretic, and analgesic advocate in many culture. According to the University College Dublin, in the testing of healthy adult, polyphenols found in willow bark (CMW) expressed significantly antiinflammatory properties through its polyphenols anti oxidant effect, by inhibiting pro inflammatory cytokines IL-1β, IL-6, and TNFα. inducing pain upon movement of joints specific to the knee and lower back.(204).
In the trail of total of 78 patients (39 willow bark extract, 39 placebo),. researcher sat the Universität Tübinge showed that Willow bark extract reduces pain, stiffness and improve physical function
(205), particular, pain reduction in short and long term usage for patients suffering from musculoskeletal disorders (MSD)(206).

5. Stinging nettle
Sting Nettle is a flower plant in the genus Urtica, belonging tothe family Urticaceae, native to Europe, Africa, Asia, and North America.The herb has been used in traditional medicine as diuretic and laxative agent and to treat diarrhea and urinary disorders, to relieve pain, treat arthritis, asthma, bronchitis, sinusitis, etc. The potent herbal medicine may be used for relive pain, especially in inflammatory rheumatic disease(207). According to the University of California, extract of Urtica dioica (the stinging nettle) prepared using accelerated solvent extraction (ASE) involving water may be used for treatment of diseases associated to inflammatory disorders as the portion displayed significant anti-inflammatory activity through inhibited the pro inflammatory pathways(208).

6. Green Tea
Green tea  has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. 
Epigallocatechin 3-gallate (EGCG), a polyphenol present in green tea, according to the Huazhong University of Science and Technology, Wuhan, exhibited beneficial therapeutic functions including antioxidant, anti-inflammatory and anti-cancer effects, through suppressing MAPK mediated inflammatory responses and oxidative stress(209).
In vascular inflammation, the phytochemical EGCG also regulated the overproduction of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in inhibition of inflammatory rheumatic activity(210).
According to the Texas Tech University Health Sciences Center, epigallocatechin gallate and green tea extract, suppressed the condition caused in part by injury, loss of cartilage structure and function, through their effects in balanced inflammatory and anti-inflammatory pathways(454,211),  probably caused by IL-1β, a major cytokine driving the inflammatory processes(455,212)(456,213).

7. Turmeric
Turmeric, a cooking spice used in many culture in South East Asian, especially in India, also has been used as herbal medicine over thousands of year as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.(457,214).
Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa slow osteoarthritis progression against bone turn over through the stimulation of interleukin (IL)-1β , downregulate the expression of inflammatory markers on osteoblasts(459,216).

The joint study St. Louis University School of Medicine and University of Nebraska Medical Center in review of research at the laboratory, translational and clinical levels data found that most the studies and trails supports the use of curcumin for various musculoskeletal disorders, including osteoarthritis, Polymyalagia Arthritis (Rheumatica),.....(458, 215).

The Belgium study of 820 patients treated with a new Curcuma extract (Flexofytol®, 4-6 capsules per day), suggested that the extract improves patient pain, articular mobility, and quality of life. Within the first 6 weeks, more than half of participants were able to discontinue analgaesic and anti-inflammatory drugs with tolerate adverse effects(461, 217)

8. Cat's claw
Cat's claw (Uncaria tomentosa), the very common herbal medicine, has been used in traditional medicine over two thousand years as a tonic, contraceptive, anti-inflammatory and infectious agent, and to treat diarrhea, rheumatic disorders, acne, diabetes, cancer and diseases of the urinary tract, etc.(462,218).
 Recently, according to the study by Case Western Reserve University, herbal and amino acid mixture containing extract of the Uncaria tomentosa, may be potentially useful as a new adjunct therapeutic/preventive agent for Arthritis or injury recovery effectively, due to its anti inflammatory(464,219) and chondroprotective activities, in up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated and inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes(463,220) as well as reducing of pro-inflammatory mediators and effectors(464,221).

The Facultad de Medicina, in the comparison of the species U guianensis and U tomentosa, found that both herbal medicine are effective in treatment of arthritis, probably through its anti-inflammatory properties in inhibited TNFalpha and PGE2 production(465,222).

8. Bromelain
Bromelain, a group of protein digesting enzymes  found in pineapples (Ananas comosus) has been used in traditional medicine as inflammatory agent and to treat pains, strains, and muscle aches and pains and ease back pain and chronic joint pain, skin diseases, etc.(467,223). The herbal medicine may be used as valuable and safe alternative to NSAIDs in patients suffering acute and chronic Arthritis from degenerative joint diseases due to its anti-inflammatory and analgesic effects(468,224).

According to the Rehabilitation Centre for Cardiovascular and Rheumatic Diseases, oral enzyme therapy (Phlogenzym-(PE)), has found effectively in treatment for patient with arthritis with high levels of pain due to signs of inflammation(469,225). 
Dr. Brien S and the research team in the study of the anti-inflammatory and analgesic properties in patient with arthritis said that more studies and trials are necessary to trials to establish the efficacy and optimum dosage for bromelain as a safer alternative or adjunctive treatment for arthritis(470,226).

9. Boswellia serrata 
 Boswellia serrata used as incense in religious and cultural ceremonies and in medicine over thousands of year may be the potential source for treatment of osteoarthritis due to its anti inflammatory(472,227), anti-arthritic and analgesic activity activity(473,228) in decreased knee pain, increased knee flexion and increased walking distance(473,228).
DR. Kizhakkedath said that formula containing Curcuma longa and Boswellia serrata extracts (CB formulation) at 500 mg administered twice a day in a directly compared with the selective COX-2 inhibitor, celecoxib at 100 mg twice a day, induced more successful symptom scoring and clinical examination(475,229).

10. Gingko
Gingko is  also known as Ginkgo biloba, one of the oldest herbal medicine in human medical history, used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders,,...(477,230).
Gingko extract, with anti inflammatory(478,231) and immune modulatory(479,232) activities may be a potential herbal medicine for treatment of osteoarthritis by inhibiting the interleukin-1 (IL-1)-stimulated human chondrocytes degeneration and MMP(matrix metalloproteinases)-1, MMP-3, and 13.causes of cartilage degradation(481,233)(482,234) according to the Postgraduate Institute of Medical Education and Research(480, 235).

11. Dan Shen
Dan Shen with the pharmaceutical name of Radix Salvia miltiorrhizae, is a bitter and slightly cold herb, used mainly in traditional Chinese medicine for tonifying blood(494,236), such as getting rid of clot blood, invigorate blood, breakup blood stasis,... through its effects on liver and heart meridians.

According to Veterinary Herbal Medicine By Susan G. Wynn, Barbara Fougère, page 349. Dan Shen induced formation of dense callus and increased activity of osteoblasts of which enhanced the improvement of bone heeling(492,237). Certain studies found in Dan Shen (Salvia miltiorrhiza) in Medicine: Volume 2. Pharmacology ..., Volume 2 edited by Xijun Yan also supported the use of Dan Shen injection for treatment of arthritis because of its anti inflammatory effect(493,238).


B.2.2. Herbal and traditional Chinese medicine formulas
1. Phytodolor (STW 1)
Phytodolor, a fixed herbal formulation containing alcoholic extracts of aspen leaves and bark (Populus tremula), common ash bark (Fraxinus excelsior), and golden rod herb (Solidago virgaurea), has been used for treatment in painful inflammatory or degenerative rheumatic diseases(483,239), probably due to its antiinflammatory, antioedematous, antioxidative and analgesic properties(483,239).
According to the University Hospital Zurich, in the review of the data base of randomized controlled trials (RCTs), STW1 can be used as non-steroidal anti-inflammatory drugs (NSAIDs) in relieving pain in patient with musculoskeletal disorders, including Rheumatica(484,240). DR. Gundermann KJ and Dr.Müller J. in the study of painful inflammatory or degenerative rheumatic diseases, said" Phytodolor (STW 1) is a reasonable alternative to NSAIDs and to cyclooxygenase(COX)-2-inhibitors such as rofecoxib"(483,239) and "STW 1 has a high drug safety"(483,239) with little side effects(486, 241).
The formula although is found to be effective in some extension in treating pain for patient with MD, some research suggested that most popular CAM therapies for pain from arthritis-related conditions, should be gone through additional high quality research, especially for herbals and homeopathy(485,242).

2. Reumalex 
Reumalex, is a herbal medicine formula containing 100 mg White Willow bark, 40 mg, Guaiacum Resin BHP, 35 mg Black Cohosh, 25 mg Extract of Sarsparilla  and 17 mg  Extract of Poplar Bark.  In a 2 months without cross-over study, in 82 subjects with chronic arthritic pain, Dr. Mills SY and the research team at the University of Exeter showed that Reumalex, the herbal medicine improved the pain symptoms through its mild analgesic effect(487,243).

3. SKI306X
SKI306X, is a herbal formula containing Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK),
According to the study by the Hanyang University Hospital for Rheumatic Diseases, SKI3006X, reduced pain and improve physical performance(498,244) by inhibited degradation of glycosaminoglycan (GAG) through its expression on  anti inflammatory(497,245)(499,246) and analgesic(499,246)properties in interleukin (IL)-1β induced gene expression in human Arthritis (497,247).

Huo-Luo-Xiao-Ling (HLXL) Dan
Huo-Luo-Xiao-Ling (HLXL) Dan is a Chinese herbal formula containing Ru Xiang (Boswellia carterii Birdw.), Mo Yao (Commiphora myrrha Engl.), Dang Gui (Angelica sinensis (Oliv.) Diels) and Dan Shen (Salvia miltiorrhiza Bge), used over thousands of year in Chinese history for treatment in alleviating pain caused rheumatoid arthritis (RA) and other inflammatory disorders(505,248)(508,249). On a Phase II clinical trial at Kernan Hospital of the University of Maryland School of Medicine, the herbal formula moderately inhibited hyperanalgesic (severe pain killing)(508,248) with no side effect in comparison to placebo(506,250).

5. Si Miao Fang
SI Miao Fang is a herbal formula comprised of Phellodendri Chines Cortex, Atractylodis rhizoma, Coicis Semen, and Achyranthis bidentatae Radix used in traditional Chinese medicine for pain relief, due to inflammation and and analgesics(509,251), through its interferes with secretion of pro-inflammatory cytokines and inflammatory mediators(512,252).


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(3) Assessment and management of polymyalgia rheumatica in older adults by Kennedy-Malone LM1, Enevold GL.(PubMed)
(4) Crowned dens syndrome misdiagnosed as polymyalgia rheumatica, giant cell arteritis, meningitis or spondylitis: an analysis of eight cases by Aouba A1, Vuillemin-Bodaghi V, Mutschler C, De Bandt M.(PubMed)
(5) [Polymyalgia rheumatica mimicking neoplastic disease--significant problem in elderly patients].
[Article in Polish] by Kwiatkowska B1, Filipowicz-Sosnowska A.(PubMed)
(6) Locked jaw in polymyalgia rheumatica by Lim SH1, McLeay G.(PubMed)
(7) Polymyalgia Rheumatica (PMR) Special Interest Group at OMERACT 11: outcomes of importance for patients with PMR by Mackie SL1, Arat S, da Silva J, Duarte C, Halliday S, Hughes R, Morris M, Pease CT, Sherman JW, Simon LS, Walsh M, Westhovens R, Zakout S, Kirwan JR.(PubMed)
(8) "An impediment to living life": why and how should we measure stiffness in polymyalgia rheumatica? by Mackie SL1, Hughes R2, Walsh M2, Day J3, Newton M3, Pease C4, Kirwan J5, Morris M6.(PubMed)
(8) A case of polymyalgia rheumatica following influenza B infection by Iwata K1, Mizuno Y2.(PubMed)
(9) HLA-DRB1 allele distribution in polymyalgia rheumatica and giant cell arteritis: influence on clinical subgroups and prognosis by Martínez-Taboda VM1, Bartolome MJ, Lopez-Hoyos M, Blanco R, Mata C, Calvo J, Corrales A, Rodriguez-Valverde V.(PubMed)
(10) HLA-DRB1 allele distribution in polymyalgia rheumatica and giant cell arteritis: influence on clinical subgroups and prognosis by Martínez-Taboda VM1, Bartolome MJ, Lopez-Hoyos M, Blanco R, Mata C, Calvo J, Corrales A, Rodriguez-Valverde V.(PubMed)
(11) Diagnosing late onset rheumatoid arthritis, polymyalgia rheumatica, and temporal arteritis in patients presenting with polymyalgic symptoms. A prospective longterm evaluation by Pease CT1, Haugeberg G, Morgan AW, Montague B, Hensor EM, Bhakta BB.(PubMed)
(12) Polymyalgia rheumatica is not seasonal in pattern and is unrelated to parvovirus b19 infection by Peris P1.(PubMed)
(13) Lack of association between infection and onset of polymyalgia rheumatica by Narváez J1, Clavaguera MT, Nolla-Solé JM, Valverde-Garcia J, Roig-Escofet D.(PubMed)
(14) Familial aggregation in giant cell arteritis and polymyalgia rheumatica: a comprehensive literature review including 4 new families by Liozon E1, Ouattara B, Rhaiem K, Ly K, Bezanahary H, Loustaud V, Letellier P, Drouet M, Vidal E.(PubMed)
(15) Statin-associated polymyalgia rheumatica. An analysis using WHO global individual case safety database: a case/non-case approach by de Jong HJ1, Saldi SR, Klungel OH, Vandebriel RJ, Souverein PC, Meyboom RH, Passier JL, van Loveren H, Cohen Tervaert JW.(PubMed)
(16) Cerivastatin-induced polymyalgia rheumatica-like illness by Goëb V, Guillemant N, Vittecoq O, Le Loët X.(PubMed)
(17) Giant cell arteritis and polymyalgia rheumatica after reexposure to a statin: a case report by de Jong HJ, Meyboom RH, Helle MJ, Klungel OH, Niskanen L, Cohen Tervaert JW.(PubMed)
(18) Analysis of the rs20541 (R130Q) polymorphism in the IL-13 gene in patients with elderly-associated chronic inflammatory diseases.[Article in English, Spanish] by Alvarez-Rodríguez L1, López-Hoyos M, Carrasco-Marín E, Mata C, Calvo-Alén J, Aurrecoechea E, Blanco R, Ruiz T, Muñoz Cacho P, Villa I, Martínez-Taboada VM.(PubMed)
(19) Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic conditions: Association of IL-1RN*2/2 genotype with polymyalgia rheumatica by Alvarez-Rodriguez L1, Carrasco-Marin E, Lopez-Hoyos M, Mata C, Fernandez-Prieto L, Ruiz-Soto M, Calvo J, Rodriguez-Valverde V, Ruiz T, Blanco R,Corrales A, Martinez-Taboada VM(PubMed)
(20) Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica by Boiardi L1, Casali B, Farnetti E, Pipitone N, Nicoli D, Cantini F, Macchioni P, Bajocchi G, Catanoso MG, Pulsatelli L, Consonni D, Salvarani C.(PubMed)
(21) [Polymyalgia rheumatica mimicking neoplastic disease--significant problem in elderly patients].
[Article in Polish]by Kwiatkowska B1, Filipowicz-Sosnowska A.(PubMed)
(22) Phagocyte dysfunction in polymyalgia rheumatica and other age-related, chronic, inflammatory conditions by Álvarez-Rodríguez L1, López-Hoyos M, Calvo-Alén J, Aurrecoechea E, Villa I, Martínez-Taboada VM.(PubMed)
(23) Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly‐onset rheumatoid arthriti by M Cutolo, C M Montecucco, L Cavagna, R Caporali, S Capellino, P Montagna, L Fazzuoli, B Villaggio, B Seriolo, and A Sulli(PMC)
(24) Dietary risk factors for the development of inflammatory polyarthritis: evidence for a role of high level of red meat consumption by Pattison DJ1, Symmons DP, Lunt M, Welch A, Luben R, Bingham SA, Khaw KT, Day NE, Silman AJ.(PubMed)
(25) Epidemiology of polymyalgia rheumatica by Cimmino MA1, Zaccaria A.(PubMed)
(26) Clinical characteristics of patients with remitting seronegative symmetrical synovitis with pitting edema compared to patients with pure polymyalgia rheumatica by Kimura M1, Tokuda Y, Oshiawa H, Yoshida K, Utsunomiya M, Kobayashi T, Deshpande GA, Matsui K, Kishimoto M.(PubMed)
(27) Procalcitonin at the onset of giant cell arteritis and polymyalgia rheumatica: the GRACG prospective study by Schmidt J1, Duhaut P, Bourgeois AM, Salle V, Smail A, Chatelain D, Betsou F, Mazière JC, Ducroix JP; Groupe de Recherche sur l'Artérite à Cellules Géantes (GRACG).(PubMed)
(28) The association of cigarette smoking with disease outcome in patients with early inflammatory polyarthritis by Harrison BJ1, Silman AJ, Wiles NJ, Scott DG, Symmons DP.(PubMed)
(29) Sex differences in temporal arteritis and polymyalgia rheumatica by Narvaez J1, Nolla-Solé JM, Valverde-García J, Roig-Escofet D.(PubMed)
(30) Current evidence for therapeutic interventions and prognostic factors in polymyalgia rheumatica: a systematic literature review informing the 2015 European League Against Rheumatism/American College of Rheumatology recommendations for the management of polymyalgia rheumatica by Dejaco C1, Singh YP2, Perel P3, Hutchings A4, Camellino D5, Mackie S6, Matteson EL7, Dasgupta B2.(PubMed)
(31) Disease patterns of rheumatology outpatients seen in a tertiary hospital serving a multi-ethnic, urban Asianpopulation in Singapore by Ng X1, Low AH, Chew LC, Chong YY, Fong KY, Lui NL, Sim E, Tan YK, Yoong J, Thumboo J.(PubMed)
(32) Rheumatic diseases in China by Zeng QY1, Chen R, Darmawan J, Xiao ZY, Chen SB, Wigley R, Le Chen S, Zhang NZ(PubMed)
(33) The epidemiology of polymyalgia rheumatica in primary care: a research protocol.by Muller S1, Hider S, Helliwell T, Bailey J, Barraclough K, Cope L, Dasgupta B, Foskett R, Hughes R, Mayson Z, Purcell C, Roddy E, Wathall S, Zwierska I, Mallen CD.(PubMed)
(34) Patient-reported outcomes in polymyalgia rheumatica. by Matteson EL1, Maradit-Kremers H, Cimmino MA, Schmidt WA, Schirmer M, Salvarani C, Bachta A, Dejaco C, Duftner C, Slott Jensen H, Poór G, Kaposi NP,Mandl P, Balint PV, Schmidt Z, Iagnocco A, Cantini F, Nannini C, Macchioni P, Pipitone N, Del Amo M, Espígol-Frigolé G, Cid MC, Martínez-Taboada VM,Nordborg E, Direskeneli H, Aydin SZ, Ahmed K, Hazelman B, Pease C, Wakefield RJ, Luqmani R, Abril A, Marcus R, Gonter NJ, Maz M, Crowson CS, Dasgupta B.(PubMed)
(35) Polymyalgia rheumatica and giant cell arteritis in older patients: diagnosis and pharmacological management by Schmidt J1, Warrington KJ.(PubMed)
(36) Visual complications of polymyalgia rheumatica (polymyalgia arteritica) by Hart FD(PubMed)
(37) Polymyalgia rheumatica and the risk of stroke: a three-year follow-up study by Kang JH1, Sheu JJ, Lin HC.(PubMed)
(38) Prevalence of ischemic complications in patients with giant cell arteritis presenting with apparently isolatedpolymyalgia rheumatica by Narváez J1, Estrada P2, López-Vives L2, Ricse M2, Zacarías A2, Heredia S2, Gómez-Vaquero C2, Nolla JM2.(PubMed)
(39) Lumbar interspinous bursitis in active polymyalgia rheumatica by Salvarani C1, Barozzi L, Boiardi L, Pipitone N, Bajocchi GL, Macchioni PL, Catanoso M, Pazzola G, Valentino M, De Luca C, Hunder GG(PubMed)
(40) Non-infectious aortitis: a report of 32 cases from a single tertiary centre in a 4-year period and literature review by Loricera J1, Blanco R1, Hernández JL2, Carril JM3, Martínez-Rodríguez I3, Canga A4, Peiró E1, Alonso-Gutiérrez J2, Calvo-Río V1, Ortiz-Sanjuán F1, Mata C1,Pina T1, González-Vela MC5, Martínez-Amador N3, González-Gay MA6.(PubMed)
(41) Cervical interspinous bursitis in active polymyalgia rheumatica by Salvarani C1, Barozzi L, Cantini F, Niccoli L, Boiardi L, Valentino M, Pipitone N, Bajocchi G, Macchioni P, Catanoso MG, Olivieri I, Hunder GG.(PubMed)
(42) Interspinous bursitis is common in polymyalgia rheumatica, but is not associated with spinal pain by Camellino D, Paparo F, Morbelli S, Cutolo M, Sambuceti G, Cimmino MA.(PubMed)
(43) Rapid development of renal failure secondary to AA-type amyloidosis in a patient with polymyalgia rheumatica by Javaid MM1, Kamalanathan M, Kon SP.(PubMed)
(44) Secondary (AA-type) amyloidosis in patients with polymyalgia rheumatica by Escribá A1, Morales E, Albizúa E, Herrero JC, Ortuño T, Carreño A, Dominguez-Gil B, Praga M.(PubMed)
(45) Presentations of perforated colonic pathology in patients with polymyalgia rheumatica: two case reports by de Silva P1, Pranesh N, Vautier G.(PubMed)
(46) Cancer in association with polymyalgia rheumatica and temporal arteritis by Haga HJ1, Eide GE, Brun J, Johansen A, Langmark F.(PubMed)
(47) Cancer risk in patients hospitalized with polymyalgia rheumatica and giant cell arteritis: a follow-up study in Sweden by Ji J1, Liu X, Sundquist K, Sundquist J, Hemminki K.(PubMed)
(48) Polymyalgia Rheumatica by  Ehab R Saad, MD, MA, FACP, FASN; Chief Editor: Herbert S Diamond, MD(Medscape)
(49) Autoimmune thyroid disease and the polymyalgia rheumatica-giant cell arteritis syndrome by Dent RG, Edwards OM.(PubMed)
(50) Giant cell arteritis and polymyalgia rheumatica: an update by González-Gay MA1, Pina T.(PubMed)
(51) [Chronic autoimmune thyroiditis and connective tissue system diseases].[Article in Slovak]by Macejová Z1, Benhatchi K, Lazúrová I.(PubMed)
(52) [Prevalence of hypothyroidism and hyperthyroidism in temporal arteritis and rhizomelic pseudopolyarthritis. A controlled study of 104 cases].[Article in French] by Juchet H1, Labarthe MP, Ollier S, Vilain C, Arlet P.(PubMed)
(53) Polymyalgia rheumatica and the risk of stroke: a three-year follow-up study by Kang JH1, Sheu JJ, Lin HC.(PubMed)
(54) Development of ischemic complications in patients with giant cell arteritis presenting with apparently isolatedpolymyalgia rheumatica: study of a series of 100 patients by Hernández-Rodríguez J1, Font C, García-Martínez A, Espígol-Frigolé G, Sanmartí R, Cañete JD, Grau JM, Cid MC(PubMed)
(55) Estimation of the symptoms for GERD by GerdQ in the patients with rheumatic diseases by Nozaki Y1, Kinoshita K1, Ri J1, Sakai K1, Shiga T1, Hino S1, Hirooka Y1, Sugiyama M1, Funauchi M1, Matsumura I1.(PubMed)
(56) (18)F-FDG PET/CT for the detection of large vessel vasculitis in patients with polymyalgia rheumatica by Lavado-Pérez C1, Martínez-Rodríguez I2, Martínez-Amador N1, Banzo I1, Quirce R1, Jiménez-Bonilla J1, De Arcocha-Torres M1, Bravo-Ferrer Z1, Jiménez-Alonso M1, López-Defilló JL1, Blanco R3, González-Gay MA3, Carril JM1.(PubMed)
(57) Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica by Unizony S1, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B, Stone JR, Stone JH.(PubMed)
(58) Methotrexate treatment in large vessel vasculitis and polymyalgia rheumatica by Spies CM1, Burmester GR, Buttgereit F.(PubMed)
(59) Risk of vascular events in patients with polymyalgia rheumatica by Hancock AT1, Mallen CD2, Muller S1, Belcher J1, Roddy E1, Helliwell T1, Hider SL1.(PubMed)
(60) Increased risk of peripheral arterial disease in polymyalgia rheumatica: a population-based cohort study by Warrington KJ1, Jarpa EP, Crowson CS, Cooper LT, Hunder GG, Matteson EL, Gabriel SE.(PubMed)
(61) Rapid development of renal failure secondary to AA-type amyloidosis in a patient with polymyalgia rheumatica by Javaid MM1, Kamalanathan M, Kon SP.(PubMed)
(62) Secondary (AA-type) amyloidosis in patients with polymyalgia rheumatica by Escribá A1, Morales E, Albizúa E, Herrero JC, Ortuño T, Carreño A, Dominguez-Gil B, Praga M.(PubMed)
(63) Development of ischemic complications in patients with giant cell arteritis presenting with apparently isolatedpolymyalgia rheumatica: study of a series of 100 patients by Hernández-Rodríguez J1, Font C, García-Martínez A, Espígol-Frigolé G, Sanmartí R, Cañete JD, Grau JM, Cid MC.(PubMed)
(64) Prevalence of ischemic complications in patients with giant cell arteritis presenting with apparently isolatedpolymyalgia rheumatica by Narváez J1, Estrada P2, López-Vives L2, Ricse M2, Zacarías A2, Heredia S2, Gómez-Vaquero C2, Nolla JM2.(PubMed)
(65) Thrombocytosis in polymyalgia rheumatica: an additional diagnostic criterion and possible risk factor for ischemic complications?by Harten P, Seyfarth B, Löffler H.(PubMed)
(66) Patients with polymyalgia rheumatica had a 2.6-fold increased risk for vascular events at a median 7.8 y by Staud R.(PubMed)
(67) Risk of vascular events in patients with polymyalgia rheumatica by Hancock AT1, Mallen CD2, Muller S1, Belcher J1, Roddy E1, Helliwell T1, Hider SL1.(PubMed)
(68) Interspinous bursitis is common in polymyalgia rheumatica, but is not associated with spinal pain by Camellino D, Paparo F, Morbelli S, Cutolo M, Sambuceti G, Cimmino MA.(PubMed)
(69) Lumbar interspinous bursitis in active polymyalgia rheumatica by Salvarani C1, Barozzi L, Boiardi L, Pipitone N, Bajocchi GL, Macchioni PL, Catanoso M, Pazzola G, Valentino M, De Luca C, Hunder GG.(PubMed)
(70)Shoulder arthritis. Distinguishing among the many causes of inflammation by Ellman MH, Brown NL, Curran JJ.(PubMed)
(71) Rheumatologic aspects of painful conditions affecting the shoulder by Curran JF, Ellman MH, Brown NL.(PubMed)
(72) Insufficiency fractures in rheumatic patients: misdiagnosis and underlying characteristics by Elkayam O1, Paran D, Flusser G, Wigler I, Yaron M, Caspi D.(PubMed)
(73) Insufficiency fractures in patients with chronic inflammatory joint diseases by Mäenpää HM1, Soini I, Lehto MU, Belt EA.(PubMed)
(74) "Chronic Epstein-Barr virus infection" syndrome and polymyalgia rheumatica by Buchwald D1, Sullivan JL, Leddy S, Komaroff AL.(PubMed)
(75) Synchronous variations of the incidence of temporal arteritis and polymyalgia rheumatica in different regions of Denmark; association with epidemics of Mycoplasma pneumoniae infection by Elling P1, Olsson AT, Elling H.(PubMed)
(76) Pain in the elderly: polymyalgia rheumatica by Loeslie V1.(PubMed)
(77) Polymyalgia rheumatica in patients with a normal erythrocyte sedimentation rate by Helfgott SM1, Kieval RI.(PubMed)
(78) Polymyalgia rheumatica without significantly increased erythrocyte sedimentation rate. A more benign syndrome by González-Gay MA1, Rodríguez-Valverde V, Blanco R, Fernández-Sueiro JL, Armona J, Figueroa M, Martínez-Taboada VM.(PubMed)
(79) Diagnosis, differential diagnosis and treatment of polymyalgia rheumatica by Nothnagl T1, Leeb BF.(PubMed)
(80) 2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative by Dasgupta B1, Cimmino MA, Kremers HM, Schmidt WA, Schirmer M, Salvarani C, Bachta A, Dejaco C, Duftner C, Jensen HS, Duhaut P, Poór G, Kaposi NP,Mandl P, Balint PV, Schmidt Z, Iagnocco A, Nannini C, Cantini F, Macchioni P, Pipitone N, Del Amo M, Espígol-Frigolé G, Cid MC, Martínez-Taboada VM,Nordborg E, Direskeneli H, Aydin SZ, Ahmed K, Hazleman B, Silverman B, Pease C, Wakefield RJ, Luqmani R, Abril A, Michet CJ, Marcus R, Gonter NJ, Maz M,Carter RE, Crowson CS, Matteson EL.(PubMed)
(81) [Thrombocytosis in progressive generalized sclerosis (scleroderma) and in other rheumatic diseases].[Article in German] by Valentini G, Chianese U, Tirri G, Giordano M.(PubMed)
(82) Early recognition improves prognosis in elderly onset RA. by Negoescu A, Ostör AJ.(PubMed)
(83) Giant cell arteritis and polymyalgia rheumatica. Review for the otolaryngologist by Ferguson BJ, Allen NB, Farmer JC Jr.(PubMed)
(84) [Polymyalgia rheumatica in daily routine practice].[Article in German] by Talke M1, Schmidt WA.(PubMed)
(85) [Late onset spondyloarthropathy misdiagnosed as polymyalgia rheumatica].[Article in French] by Kouassi Djaha JM1, Jenvrin C, Dupont MP, Steiner J, de Bandt M.(PubMed)
(86) Late onset spondyloarthropathy mimicking polymyalgia rheumatica by Aydeniz A1, Altındağ O, Oğüt E, Gürsoy S.(PubMed)
(87) [Polymyalgia rheumatica in daily routine practice].[Article in German] by Talke M1, Schmidt WA(PubMed)
(88) Lumbar interspinous bursitis in active polymyalgia rheumatica by Salvarani C1, Barozzi L, Boiardi L, Pipitone N, Bajocchi GL, Macchioni PL, Catanoso M, Pazzola G, Valentino M, De Luca C, Hunder GG.(PubMed)
(89) Joint involvement in patients with early polymyalgia rheumatica using high-resolution ultrasound and its contribution to the EULAR/ACR 2012 classification criteria for polymyalgia rheumatica by Weigand S1, Ehrenstein B, Fleck M, Hartung W.(PubMed)
(90) Presenting features of polymyalgia rheumatica (PMR) and rheumatoid arthritis with PMR-like onset: a prospective study by Caporali R1, Montecucco C, Epis O, Bobbio-Pallavicini F, Maio T, Cimmino MA.(PubMed)
(91) The effect of weight loss and dietary fatty acids on inflammation by Devaraj S1, Kasim-Karakas S, Jialal I.(PubMed)
(92) Effects of the Dietary ω3:ω6 Fatty Acid Ratio on Body Fat and Inflammation in Zebrafish (Danio rerio). by Powell ML1, Pegues MA2, Szalai AJ2, Ghanta VK3, D'Abramo LR4, Watts SA3.(PubMed)
(93) ω3-polyunsaturated fatty acids suppress lipoprotein-associated phospholipase A2 expression in macrophages and animal models vt Li Z1, Ren W1, Han X1, Liu X1, Wang G1, Zhang M1, Pang D1, Ouyang H1, Tang X1.(PubMed)
(94) Overview of Omega-3 Fatty Acid Therapies by J. Chris Bradberry, PharmD and Daniel E. Hilleman, PharmD(PubMed)
(95) Health implications of high dietary omega-6 polyunsaturated Fatty acids by Patterson E1, Wall R, Fitzgerald GF, Ross RP, Stanton C.(PubMed)
(96) Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents by Holt EM1, Steffen LM, Moran A, Basu S, Steinberger J, Ross JA, Hong CP, Sinaiko AR.(PubMed)
(97) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults. by Bhupathiraju SN1, Tucker KL.(PubMed)
(98) [Role of diet on chronic inflammation prevention and control - current evidences].[Article in Portuguese] by Geraldo JM1, Alfenas Rde C.(PubMed)
(99) [Dietary factors and metabolic syndrome].[Article in Portuguese] by Steemburgo T1, Dall'Alba V, Gross JL, Azevedo MJ.(PubMed)
(100) A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolicsyndrome by Xiao S1, Fei N, Pang X, Shen J, Wang L, Zhang B, Zhang M, Zhang X, Zhang C, Li M, Sun L, Xue Z, Wang J, Feng J, Yan F, Zhao N, Liu J, Long W, Zhao L.(PubMed)
(101) Clinical characteristics of patients with remitting seronegative symmetrical synovitis with pitting edema compared to patients with pure polymyalgia rheumatica by Kimura M1, Tokuda Y, Oshiawa H, Yoshida K, Utsunomiya M, Kobayashi T, Deshpande GA, Matsui K, Kishimoto M.(PubMed)
(102) A Systematic Review of the Acute Effects of Exercise on Immune and Inflammatory Indices in Untrained Adults by Brown WM1, Davison GW1, McClean CM1, Murphy MH1.(PubMed)
(103) Effect of soy nuts and equol status on blood pressure, lipids and inflammation in postmenopausal women stratified by metabolic syndrome status by Acharjee S1, Zhou JR2, Elajami TK1, Welty FK3.(PubMed)
(104) Effect of soy nuts on adhesion molecules and markers of inflammation in hypertensive and normotensive postmenopausal women by Nasca MM1, Zhou JR, Welty FK.(PubMed)
(105) Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronicinflammation. by Shen CL1, Yeh JK, Samathanam C, Cao JJ, Stoecker BJ, Dagda RY, Chyu MC, Dunn DM, Wang JS.(PubMed)
(106) Evaluation of the anti-inflammatory and analgesic effects of green tea (Camellia sinensis) in mice by Mota MA1, Landim JS1, Targino TS1, Silva SF1, Silva SL1, Pereira MR1(PubMed)
(107) Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss). by Sheikhzadeh N1, Nofouzi K, Delazar A, Oushani AK.(PubMed)
(108) Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis by Rosillo MÁ1, Alcaraz MJ2, Sánchez-Hidalgo M1, Fernández-Bolaños JG3, Alarcón-de-la-Lastra C1, Ferrándiz ML4.(PubMed)
(109) Antinociceptive and anti-inflammatory effects of olive oil (Olea europeae L.) in mice. by Eidi A1, Moghadam-kia S, Moghadam JZ, Eidi M, Rezazadeh S.(PubMed)
(110) Chemistry and health of olive oil phenolics by Cicerale S1, Conlan XA, Sinclair AJ, Keast RS.(PubMed)
(111) In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation by Wang S1, Wu D, Lamon-Fava S, Matthan NR, Honda KL, Lichtenstein AH.(PubMed)
(112) Reduction in dietary omega-6 polyunsaturated fatty acids: eicosapentaenoic acid plus docosahexaenoic acid ratio minimizes atherosclerotic lesion formation and inflammatory response in the LDL receptor null mouse by Wang S1, Wu D, Matthan NR, Lamon-Fava S, Lecker JL, Lichtenstein AH.(PubMed)
(113) In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway by Comalada M1, Camuesco D, Sierra S, Ballester I, Xaus J, Gálvez J, Zarzuelo A.(PubMed)
(114) Health effects of quercetin: from antioxidant to nutraceutical by Boots AW1, Haenen GR, Bast A.(PubMed)
(115) Compounds derived from epigallocatechin-3-gallate (EGCG) as a novel approach to the prevention of viral infections by Hsu S.(PubMed)
(116) Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF-kappa B pathways by Xiao J1, Ho CT, Liong EC, Nanji AA, Leung TM, Lau TY, Fung ML, Tipoe GL.(PubMed)
(116) (-)-Epigallocatechin-3-gallate (EGCG) attenuates functional deficits and morphological alterations by diminishing apoptotic gene overexpression in skeletal muscles after sciatic nerve crush injury by Renno WM1, Al-Maghrebi M, Al-Banaw A(PubMed)).
(118) Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS) by Nicol LM1, Rowlands DS, Fazakerly R, Kellett J.(PubMed)
(119) Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva®): a randomised, placebo-controlled trial by Drobnic F1, Riera J1, Appendino G2, Togni S3, Franceschi F3, Valle X4, Pons A5, Tur J5.(PubMed)
(120) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature.by Anand P1, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB.(PubMed)
(121) Resveratrol nanoparticle system improves dissolution properties and enhances the hepatoprotective effect of resveratrol through antioxidant and anti-inflammatory pathways by Lee CW1, Yen FL, Huang HW, Wu TH, Ko HH, Tzeng WS, Lin CC.(PubMed)
(122) Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain by Tillu DV1, Melemedjian OK, Asiedu MN, Qu N, De Felice M, Dussor G, Price TJ.(PubMed)
(123) Boswellia serrata, a potential antiinflammatory agent: an overview by Siddiqui MZ1.(PubMed)
(124) Potentiation of antinociceptive effect of NSAIDs by a specific lipooxygenase inhibitor, acetyl 11-keto-betaboswellic acid by Bishnoi M1, Patil CS, Kumar A, Kulkarni SK.(PubMed)
(125) Anti-inflammatory and analgesic effects of cucurbitacins from Wilbrandia ebracteata by Peters RR1, Farias MR, Ribeiro-do-Valle RM.(PubMed)
(126) Nitric oxide and cyclooxygenase may participate in the analgesic and anti-inflammatory effect of thecucurbitacins fraction from Wilbrandia ebracteata by Peters RR1, Baier Krepsky P, Siqueira-Junior J, da Silva Rocha JC, Marques Bezerra M, de Albuquerque Ribeiro R, de Brum-Fernandes AJ, Rocha Farias M,Castro da Rocha FA, Ribeiro-do-Valle RM(PubMed)
(176,127) Free Radicals, Antioxidants in Disease and Health by Lien Ai Pham-Huy,1 Hua He,2 and Chuong Pham-Huy3(PMC)
(177,128) Superoxide Anion and Its Functions(Beta Forces)
(178,129) Free radicals and antioxidants in normal physiological functions and human disease by Valko M1, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J.(PubMed)
(179,130) Free radicals, metals and antioxidants in oxidative stress-induced cancer by Valko M1, Rhodes CJ, Moncol J, Izakovic M, Mazur M.(PubMed)
(131) Muscle pain and serum creatine kinase are not associated with low serum 25(OH) vitamin D levels in patients receiving statins by Kurnik D1, Hochman I, Vesterman-Landes J, Kenig T, Katzir I, Lomnicky Y, Halkin H, Loebstein R.
(180,132) Cellular immunity in osteoarthritis: novel concepts for an old disease by Liossis SN1, Tsokos GC.(PubMed)
(182,133) Free Radicals, Antioxidants in Disease and Health by Lien Ai Pham-Huy,1 Hua He,2 and Chuong Pham-Huy3(PMC)
(134) Essential role of vitamin C and zinc in child immunity and health by Maggini S1, Wenzlaff S, Hornig D.(PubMed)
(183,135) New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate by Hae-Suk Kim,a Michael J. Quon,c and Jeong-a Kima,b(PMC)
(184,136) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications by Singh BN1, Shankar S, Srivastava RK.(PubMed)
(137) Vitamin E and immunity by Moriguchi S1, Muraga M.(PubMed)
(188,138) Green tea: a new option for the prevention or control of osteoarthritis by Katiyar SK, Raman C.(PubMed)
(190,139) Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans role of oxidative stress by K Esposito, F Nappo, R Marfella, G Giugliano, F Giugliano, M Ciotola(Circulation)
(193,140) Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise by Ahmed S1.(PubMed)
(141) Associations between glucosamine and chondroitin supplement use and biomarkers of systemic inflammation by Kantor ED1, Lampe JW, Navarro SL, Song X, Milne GL, White E.(PubMed)
(142) [A role of melatonin in the treatment of low back pain].[Article in Russian] by Kurganova YM, Danilov AB.(PubMed)
(196,143)
(144) Taltirelin, a thyrotropin-releasing hormone analog, alleviates mechanical allodynia through activation of descending monoaminergic neurons in persistent inflammatory pain by Eto K1, Kim SK, Nabekura J, Ishibashi H.(PubMed)
(145) Methylsulfonylmethane inhibits NLRP3 inflammasome activation by Ahn H1, Kim J1, Lee MJ1, Kim YJ2, Cho YW3, Lee GS4.(PubMed)
(199, 146) Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. by Kim LS1, Axelrod LJ, Howard P, Buratovich N, Waters RF.(PubMed)
(200, 147) Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study by Debbi EM1, Agar G, Fichman G, Ziv YB, Kardosh R, Halperin N, Elbaz A, Beer Y, Debi R.(PubMed)
(148) [Fasting as part of a naturopathic treatment approach for polymyalgia rheumatica].[Article in German] by Stange R1, Pflugbeil C.(PubMed)
(149)[Progression of intestinal secretory immunoglobulin A and the condition of the patients during naturopathic therapy and fasting therapy].[Article in German] by Beer AM1, Rüffer A, Balles J, Ostermann T.(PubMed)
(150) Dietary protein recommendations and the prevention of sarcopenia Protein, amino acid metabolism and therapy by Douglas Paddon-Jones and Blake B. Rasmussen(PubMed)
(151) Similar effects of leucine rich and regular dairy products on muscle mass and functions of older polymyalgia rheumatica patients: a randomized crossover trial. by Björkman MP1, Pilvi TK, Kekkonen RA, Korpela R, Tilvis RS.(PubMed)
(152) Effective control of polymyalgia rheumatica with tocilizumab by Al Rashidi A1, Hegazi MO, Mohammad SA, Varghese A.(PubMed)
(153) Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica by Unizony S1, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B, Stone JR, Stone JH.(PubMed)
(154) Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica by Gabriel SE1, Sunku J, Salvarani C, O'Fallon WM, Hunder GG.(PubMed)
(155) Polymyalgia rheumatica and corticosteroids: how much for how long? by Behn AR, Perera T, Myles AB.(PubMed)
(156) Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans by Bjarnason I1, Hayllar J, MacPherson AJ, Russell AS.(PubMed)
(157) Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica by Gabriel SE1, Sunku J, Salvarani C, O'Fallon WM, Hunder GG.(PubMed)
(158) Ultrasonography of the glenohumeral joints--a helpful instrument in differentiation in elderly onset rheumatoid arthritis and polymyalgia rheumatica by Lange U1, Piegsa M, Teichmann J, Neeck G.(PubMed)
(283,159) Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease by Kirsty Brown,† Daniella DeCoffe,† Erin Molcan, and Deanna L. Gibson(PubMed)
(160) Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages. by Shin JH1, Ryu JH, Kang MJ, Hwang CR, Han J, Kang D.(PubMed)
(161) aged black garlic exerts anti-inflammatory effects by decreasing no and proinflammatory cytokine production with less cytoxicity in LPS-stimulated raw 264.7 macrophages and LPS-induced septicemia mice. by Kim MJ1, Yoo YC, Kim HJ, Shin SK, Sohn EJ, Min AY, Sung NY, Kim MR.(PubMed)
(162) Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type. by Justo OR1, Simioni PU2, Gabriel DL2, Tamashiro WM2, Rosa Pde T3, Moraes ÂM4.(PubMed)
(163) Gingerols and shogaols: Important nutraceutical principles from ginger by Semwal RB1, Semwal DK1, Combrinck S2, Viljoen AM3.(PubMed)
(164) Effect of citrus polyphenol- and curcumin-supplemented diet on inflammatory state in obese cats by Leray V1, Freuchet B, Le Bloc'h J, Jeusette I, Torre C, Nguyen P.(PubMed)
(165) Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis by Ramadan G1, Al-Kahtani MA, El-Sayed WM.(PubMed)
(166) Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts by Lombardo Bedran TB1, Palomari Spolidorio D2, Grenier D3.(PubMed)
(167) Antiinflammatory action of EGCG, the main component of green tea, through STAT-1 inhibition by Tedeschi E1, Suzuki H, Menegazzi M.(PubMed)
(168) Antioxidant potential of green and black tea determined using the ferric reducing power (FRAP) assay by Langley-Evans SC1.(PubMed)
(169) Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2,3-Dioxygenase Expressing Dendritic Cells and the Nuclear Factor, Erythroid 2-Like 2 Antioxidant Pathway by Min SY1, Yan M1, Kim SB2, Ravikumar S3, Kwon SR4, Vanarsa K3, Kim HY5, Davis LS1, Mohan C3(PubMed)
(362,170)
(171) A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica by Healey JH1, Paget SA, Williams-Russo P, Szatrowski TP, Schneider R, Spiera H, Mitnick H, Ales K, Schwartzberg P.(PubMed)
(172) An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis by Ryan SM1, McMorrow J, Umerska A, Patel HB, Kornerup KN, Tajber L, Murphy EP, Perretti M, Corrigan OI, Brayden DJ.(PubMed)
(173) Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush fractures. A double blind, placebo-controlled clinical study by Lyritis GP1, Paspati I, Karachalios T, Ioakimidis D, Skarantavos G, Lyritis PG.(PubMed)
(174) Analgesic effect of salmon calcitonin suppositories in patients with acute pain due to recent osteoporotic vertebral crush fractures: a prospective double-blind, randomized, placebo-controlled clinical study by Lyritis GP1, Ioannidis GV, Karachalios T, Roidis N, Kataxaki E, Papaioannou N, Kaloudis J, Galanos A.(PubMed)
(362,175) Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression by Musumeci G, Trovato FM, Pichler K, Weinberg AM, Loreto C, Castrogiovanni P.(PubMed)
(364,176) A pilot double-blinded, randomized, clinical trial of topical virgin olive oil versus piroxicam gel in osteoarthritis of the knee.in Bohlooli S1, Jastan M, Nakhostin-Roohi B, Mohammadi S, Baghaei Z.(PubMed)
(177) An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases by Lorente-Cebrián S1, Costa AG, Navas-Carretero S, Zabala M, Laiglesia LM, Martínez JA, Moreno-Aliaga MJ.(PubMed)
(178) Analgesia enhancement and prevention of tolerance to morphine: beneficial effects of combined therapy withomega-3 fatty acids by Escudero GE1, Romañuk CB2, Toledo ME1, Olivera ME2, Manzo RH2, Laino CH1.(PubMed)
(179) Diet-induced changes in n-3- and n-6-derived endocannabinoids and reductions in headache pain and psychological distress by Ramsden CE1, Zamora D2, Makriyannis A3, Wood JT3, Mann JD4, Faurot KR2, MacIntosh BA5, Majchrzak-Hong SF6, Gross JR7, Courville AB8, Davis JM9,Hibbeln JR6.(PubMed)
(325,180) Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis by Yazar M1, Sarban S, Kocyigit A, Isikan UE.(PubMed)
(325,181) Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis by Yazar M1, Sarban S, Kocyigit A, Isikan UE.(PubMed)
(182) Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy by Mentes O1, Harlak A, Yigit T, Balkan A, Balkan M, Cosar A, Savaser A, Kozak O, Tufan T.(PubMed)
(183) [Relief of neuropathic pain with intravenous magnesium].[Article in Japanese] by Tanaka M1, Shimizu S, Nishimura W, Mine O, Akatsuka M, Inamori K, Mori H.(PubMed)
(184) Pre-emptive peritonsillar infiltration of magnesium sulphate and ropivacaine vs. ropivacaine or magnesium alone for relief of post-adenotonsillectomy pain in children by Sun J1, Wu X2, Zhao X1, Chen F1, Wang W3.(PubMed)
(185) Effects of magnesium depletion on inflammation in chronic disease by Nielsen FH1.(PubMed)
(186) Antioxidant therapy for pain relief in patients with chronic pancreatitis: systematic review and meta-analysis by Cai GH1, Huang J, Zhao Y, Chen J, Wu HH, Dong YL, Smith HS, Li YQ, Wang W, Wu SX.(PubMed)
(187) Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: a systematic review and meta-analysis by Talukdar R1, Murthy HV2, Reddy DN3.(PubMed)
(188) Host selenium deficiency increases the severity of chronic inflammatory myopathy in Trypanosoma cruzi-inoculated mice by Gomez RM1, Solana ME, Levander OA.(PubMed)
(330,189) Copper-salicylate gel for pain relief in osteoarthritis: a randomised controlled trial.Shackel NA1, Day RO, Kellett B, Brooks PM.(PubMed)
(332, 190) Effect of a topical copper indomethacin gel on inflammatory parameters in a rat model of osteoarthritis by Yassin NZ1, El-Shenawy SM1, Abdel-Rahman RF1, Yakoot M2, Hassan M3, Helmy S4.(PubMed)
(191) Associations of Dietary and Serum Copper with Inflammation, Oxidative Stress, and Metabolic Variables in Adults1,2 by Simona Bo3,*, Marilena Durazzo3, Roberto Gambino3, Carlo Berutti4,
Nadia Milanesio3, Antonio Caropreso4, Luigi Gentile5, Maurizio Cassader3,Paolo Cavallo-Perin3, and  Gianfranco Pagano3(The journal of nutrition)
(192) Vitamin D for the treatment of chronic painful conditions in adults by Straube S1, Derry S, Moore RA, McQuay HJ.(PubMed)
(193) Vitamin D Deficiency Linked to Depression, Pain, Inflammatory Bowel Disease, and Breast Cancer by Dr. Mercola
(194) Comfrey: a clinical overview by Staiger C1.(PubMed)
(195) Comfrey root: from tradition to modern clinical trials by Staiger C1.(PubMed)
(196) In vivo wound healing effects of Symphytum officinale L. leaves extract in different topical formulations by Araújo LU1, Reis PG, Barbosa LC, Saúde-Guimarães DA, Grabe-Guimarães A, Mosqueira VC, Carneiro CM, Silva-Barcellos NM.(PubMed)
(197) Alteration of anti-inflammatory activity of Harpagophytum procumbens (devil's claw) extract after external metabolic activation with S9 mix by Hostanska K1, Melzer J, Rostock M, Suter A, Saller R.(PubMed)
(198) [Devil's claw extract as an example of the effectiveness of herbal analgesics].[Article in German] by Chrubasik S1.(PubMed)
(199) Inhibitory effects of devil's claw (secondary root of Harpagophytum procumbens) extract and harpagoside on cytokine production in mouse macrophages by Inaba K1, Murata K, Naruto S, Matsuda H.(PubMed)
(200) A feasibility study of valerian extract for sleep disturbance in person with arthritis by Taibi DM1, Bourguignon C, Gill Taylor A.(PubMed)
(201) Non-pharmacological interventions for fatigue in rheumatoid arthritis by Cramp F1, Hewlett S, Almeida C, Kirwan JR, Choy EH, Chalder T, Pollock J, Christensen R.(PubMed)
(202) Anti-inflammatory activity of the topical preparation of Valeriana wallichii and Achyranthes aspera leaves by Khuda F1, Iqbal Z, Khan A, Zakiullah, Nasir F, Shah Y.(PubMed)
(203) Antimicrobial and anti-inflammatory activities of leaf extract of Valeriana wallichii DC by Khuda F1, Iqbal Z, Zakiullah, Khan A, Nasir F.(PubMed)
(204) An in vivo study examining the antiinflammatory effects of chamomile, meadowsweet, and willow bark in a novel functional beverage by Drummond EM1, Harbourne N, Marete E, Jacquier JC, O'Riordan D, Gibney ER.(PubMed)
(205) Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial by Schmid B1, Lüdtke R, Selbmann HK, Kötter I, Tschirdewahn B, Schaffner W, Heide L.(PubMed)
(206) Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain by Uehleke B1, Müller J, Stange R, Kelber O, Melzer J.(PubMed)
(207) Plant food supplements with anti-inflammatory properties: a systematic review (II). by Di Lorenzo C1, Dell'Agli M, Badea M, Dima L, Colombo E, Sangiovanni E, Restani P, Bosisio E.(PubMed)
(208) Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders by Johnson TA1, Sohn J, Inman WD, Bjeldanes LF, Rayburn K.(PubMed)
(209) Epigallocatechin-3-gallate attenuates lipopolysaccharide-induced mastitis in rats via suppressing MAPK mediated inflammatory responses and oxidative stress by Chen J1, Xu J1, Li J1, Du L1, Chen T2, Liu P1, Peng S1, Wang M1, Song H3.(PubMed)
(210) Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis by Riegsecker S1, Wiczynski D, Kaplan MJ, Ahmed S.(PubMed)
(454,211) Dietary polyphenols and mechanisms of osteoarthritis by Shen CL1, Smith BJ, Lo DF, Chyu MC, Dunn DM, Chen CH, Kwun IS.(PubMed)
(455,212) Green tea: a new option for the prevention or control of osteoarthritis by Katiyar SK, Raman C.(PubMed)
(456,213) Epigallocatechin-3-gallate selectively inhibits interleukin-1beta-induced activation of mitogen activated protein kinase subgroup c-Jun N-terminal kinase in human osteoarthritis chondrocytes by Singh R1, Ahmed S, Malemud CJ, Goldberg VM, Haqqi TM.(PubMed)
(457,214) Popular #Herbs - Turmeric (Curcuma longa) by Kyle J. Norton
(458,215) Role of Curcumin in Common Musculoskeletal Disorders: a Review of Current Laboratory, Translational, and Clinical Data by Peddada KV1, Peddada KV2, Shukla SK3, Mishra A3, Verma V4.(PubMed)
(459,216) Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis by Yeh CC1, Su YH2, Lin YJ2, Chen PJ2, Shi CS3, Chen CN2, Chang HI2.(PubMed)(461,217) A new curcuma extract (flexofytol®) in osteoarthritis: results from a belgian real-life experience by Appelboom T1, Maes N2, Albert A3.(PubMed)
(462,218) Cat's claw (Uncaria tomentosa) by Kyle J. Norton
(464,219) Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis by Hardin SR1.(PubMed)
(463,220) Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes by Akhtar N1, Miller MJ, Haqqi TM.(PubMed)
(464,221) Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis by Hardin SR1.(PubMed)
(465,222) Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis by Piscoya J1, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJ, Sandoval M.(PubMed)
(467,223) Popular #Herbs - Bromelain by Kyle J. Norton
(468,224) A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain by Conrozier T, Mathieu P, Bonjean M, Marc JF, Renevier JL, Balblanc JC.(PubMed)
(469,225) Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs by Klein G1, Kullich W, Schnitker J, Schwann H.(PubMed)
(470,226) Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies by Brien S, Lewith G, Walker A, Hicks SM, Middleton D.(PubMed)
(472,227) Boswellia Serrata, A Potential Antiinflammatory Agent: An Overview by M. Z. Siddiqui(PMC)
(473,228) Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial by Kimmatkar N1, Thawani V, Hingorani L, Khiyani R.(PubMed)
(475,229) Clinical evaluation of a formulation containing Curcuma longa and Boswellia serrata extracts in the management of knee osteoarthritis by Kizhakkedath R1.(PubMed)
(477,230) Popular Herbs - Ginkgo biloba by Kyle J. Norton
(478,231) Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis by Venkata S. Kotakadi,† Yu Jin,† Anne B. Hofseth, Lei Ying, Xiangli Cui, Suresh Volate, Alexander Chumanevich, Patricia A. Wood,1 Robert L. Price,2 Anna McNeal,2 Udai P. Singh,2 Narendra P. Singh,2 Mitzi Nagarkatti,2 Prakash S. Nagarkatti,2 Lydia E. Matesic,3 Karine Auclair,4 Michael J. Wargovich,5 and Lorne J. Hofseth(PMC)
(479,232) Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo by Parsad D1, Pandhi R, Juneja A.(PubMed)
(481,233) Inhibitory effects of EGb761 on the expression of matrix metalloproteinases (MMPs) and cartilage matrix destruction by Wang X1, Zhao X, Tang S.(PubMed)
(482,234) EGb761 inhibits inflammatory responses in human chondrocytes and shows chondroprotection in osteoarthritic rat knee by Chen YJ1, Tsai KS, Chiu CY, Yang TH, Lin TH, Fu WM, Chen CF, Yang RS, Liu SH.(PubMed)
(480,235) Ginkgo biloba extract individually inhibits JNK activation and induces c-Jun degradation in human chondrocytes: potential therapeutics for osteoarthritis by Ho LJ1, Hung LF2, Liu FC3, Hou TY3, Lin LC4, Huang CY2, Lai JH5.(PubMed)
(492,236) Veterinary Herbal Medicine By Susan G. Wynn, Barbara Fougère, page 349.
(493,237) Dan Shen (Salvia miltiorrhiza) in Medicine: Volume 2. Pharmacology ..., Volume 2 edited by Xijun Yan 
(493,238) Dan Shen (Salvia miltiorrhiza) in Medicine: Volume 2. Pharmacology ..., Volume 2 edited by Xijun Yan 
(483,239) Phytodolor--effects and efficacy of a herbal medicine by Gundermann KJ1, Müller J.(PubMed)
(484,240) Phytodolor® in musculoskeletal disorders: re-analysis and meta-analysis by Uehleke B1, Brignoli R, Rostock M, Saller R, Melzer J.(PubMed)
(486,241) EFFECT OF A PROPRIETARY HERBAL MEDICINE ON THE RELIEF OF CHRONIC ARTHRITIC PAIN: A DOUBLE-BLIND STUDY by S. Y. MILLS, R. K. JACOBY*, M. CHACKSFIELD and M. WILLOUGHBY(Rheumatology)
(485,242) Selected CAM therapies for arthritis-related pain: the evidence from systematic reviews.
Soeken KL1.(PubMed)
(487,243) Effect of a proprietary herbal medicine on the relief of chronic arthritic pain: a double-blind study by Mills SY1, Jacoby RK, Chacksfield M, Willoughby M.(PubMed)
(498,244) SKI306X inhibition of glycosaminoglycan degradation in human cartilage involves down-regulation of cytokine-induced catabolic genes by Choi CH1, Kim TH2, Sung YK2, Choi CB2, Na YI3, Yoo H4, Jun JB2.(PubMed)
(497,245) Assessment of comparative pain relief and tolerability of SKI306X compared with celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, double-dummy, phase III, noninferiority clinical trial by Song YW1, Lee EY, Koh EM, Cha HS, Yoo B, Lee CK, Baek HJ, Kim HA, Suh YI, Kang SW, Lee YJ, Jung HG.(PubMed)
(499,246) Effects of SKI306X on arachidonate metabolism and other inflammatory mediators by Kim JH1, Ryu KH, Jung KW, Han CK, Kwak WJ, Cho YB.(PubMed)
(497,247) Assessment of comparative pain relief and tolerability of SKI306X compared with celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, double-dummy, phase III, noninferiority clinical trial by Song YW1, Lee EY, Koh EM, Cha HS, Yoo B, Lee CK, Baek HJ, Kim HA, Suh YI, Kang SW, Lee YJ, Jung HG.(PubMed)
(505,248) Chinese Herbal Formula Huo-Luo-Xiao-Ling Dan Protects against Bone Damage in Adjuvant Arthritis by Modulating the Mediators of Bone Remodeling by Siddaraju M. Nanjundaiah,1 David Y.-W. Lee,2 Brian M. Berman,3 and Kamal D. Moudgil(Hindawi Publishing Corporation)
(508,249) Anti-hyperalgesic and anti-inflammatory effects of the modified Chinese herbal formula Huo Luo Xiao Ling Dan (HLXL) in rats by Lao L1, Fan AY, Zhang RX, Zhou A, Ma ZZ, Lee DY, Ren K, Berman B.(PubMed)
(506, 250) Dose Escalation Study Of Chinese Herbs In Osteoarthritis Of The Knee (TCM-OAK)(Clinical trial. Gov)
(509,251) Experimental Study on Anti-Inflammatory Effect and Analgesic Effect of Simiao Powder by Jing Yun, Li weilin
(512,252) Treatment with SiMiaoFang, an anti-arthritis chinese herbal formula, inhibits cartilage matrix degradation in osteoarthritis rat model by Xu Y1, Liu Q, Liu ZL, Lim L, Chen WH, Lin N.(PubMed)