Neuralgia

Neuralgia is defined as a condition of a sudden and heavy attacks of pain that follows the path of a nerve or nerves as a result of a change in neurological structure or function due to irritation or damage to the nerves without stimulating pain receptor (nociceptor) cells. the disease affects about 2%–3% of the population.

I. Symptoms
1. In the study to evaluate the symptoms of neuralgia effect on the patient with postherpetic neuralgia (PHN), scientists at Policy Analysis Inc, showed that only about one half had taken prescription medication for shingles pain during the prior week; dosages were typically low. Mean average, worst, least, and current pain caused by shingles (0- to 10-point scale) was 4.6 (+/-2.1), 6.0 (+/-2.4), 2.9 (+/-2.3), and 4.0 (+/-2.7), respectively. Mean pain interference with general activity, mood, relations with other people, sleep, and enjoyment of life (0- to 10-point scale) was 3.7 (+/-3.1), 4.3 (+/-2.9), 3.0 (+/-2.8), 3.8 (+/-2.9), and 4.5 (+/-3.1), respectively. The mean EQ-5D health index score was 0.61; respondents rated their overall health as 65.7 (+/-21.1) on a 100-point scale. PHN causes substantial pain, dysfunction, and poor health-related quality of life in older persons, many of whom might be suboptimally treated(a).

2. Mechanical allodynia and cold hyperalgesia(13)



II. Causes and Risk factors
A. Causes
1. Smoke, smell, dust and cold air
Dr. Moritsch E and  Mitschke H. in the study of Surgical elimination of endonasal triggerpoints of a trigeminal neuralgia caused by cauterization showed that a severe injury by fluid Ammonia of the nasal mucosa resulted with a strong irritation of the 1. and 2. branch of the trigeminus nerve with sudden and heavy attacks of pain. The region below the head of the right inferior nasal concha was detected as a trigger zone for smoke, smell, dust and cold air. Local anaesthesia stopped the attacks(1)

2. Chronic renal insufficiency
Chronic renal insufficiency, the slow loss of kidney function over time, are often accompanied by neuralgia. Peripheral nerve disorders distort or interrupt the messages between the brain and the rest of the body as a result of kidney damage of that can led neuralgia, as a result of waste accumulation in the blood.

3. Infection
Certain infections can lead to neuralgia
a. Facial herpes zoster infection
Occipital neuralgia is a pain syndrome which may usually be induced by spasms of the cervical muscles or trauma to the greater or lesser occipital nerves. Scientist(s) at the Kyoto University in the study of a 74-year-old male experienced sudden-onset severe headache in the occipital area showed that the pain was localized to the distribution of the right side of the greater occipital nerve, and palpation of the right greater occipital nerve reproduces the pain. He was diagnosed with occipital neuralgia according to ICHD-II criteria. A few days later, the occipital pain was followed by reddening of the skin and the appearance, of varying size, of vesicles on the right side of his face (the maxillary nerve and the mandibular nerve region). This was diagnosed as herpes zoster.(2)

b. Human immunodeficiency virus (HIV)
Dr. Louis E and the team at the Hôpital Sainte-Anne, in the study of Bilateral amyotrophic neuralgia (Parsonage Turner syndrome) with HIV seroconversion reported that a unusual case of neuralgic amyotrophy (NA) occurring during the seroconversion stage of an HIV infection. Combined with previously published cases, our observation suggests that NA associated with HIV could belong to the group of early multiplex mononeuritis. Neurologists should be aware of HIV infection when managing a patient with NA(3).


c. Lyme disease
In the report of a 55-year-old woman developed severe unilateral headaches, periocular numbness, and Horner syndrome after presenting with symptoms consistent with Lyme disease was constituted a diagnosis of Raeder paratrigeminal neuralgia(4)

d. Etc.

4. Diabetes
Diabetes are associated with  femoral neuralgia, as a result of excessive sugar levels in the blood stream. Dr. Simmat G. and the team in the study of A retrospective study allowed us to work out an original method for an essentially clinical approach of the correlation between femoral neuropathy and diabetes mellitus.(5)

5. Surgery
Certain surgery such as herniorrhaphy, appendectomy, nephrectomy, gynecological surgery, removal of bone from the inner table of the iliac crest, may increase the risk of neuralagia. In the frequent cases attributable to previous surgery the retroperitoneal resection of the nerves is advocated instead of a local revision, which is usually unsuccessful due to the impossibility of finding and restoring the fine nerves in a dense scar.(6)

6. Hypothyroidism
In the study of Painful neuropathy in subclinical hypothyroidism, Dr. Penza P, and the team at National Neurological Institute Carlo Besta showed that Subclinical hypothyroidism is a possible cause of sensory neuropathy and hormone replacement therapy can prompt nerve regeneration(7).

7. Multiple sclerosis 
Many patients with multiple sclerosis (MS) are siad to be associated with trigeminal neuralgia (TN). researchers at Università La Sapienza found that the most likely cause of MS-related TN is a pontine plaque damaging the primary afferents. Nevertheless, in some patients a neurovascular contact may act as a concurring mechanism. The other sensory disturbances, including ongoing pain and dysaesthesia, may arise from damage to the second-order neurons in the spinal trigeminal complex.(8)

8. Porphyria
Porphyrias represent a group of inherited or acquired disorders that involve enzymes that participate in heme synthesis. Acute manifestations affect the nervous system resulting in abdominal pain, vomiting, acute neuropathy, seizures, and mental disorders(9)


9. Brian and spiral tumors
In a report of Trigeminal neuralgia (TN) is often secondary to an underlying structural cause, frequently compression of the fifth nerve root by an ectatic artery. This unusual set of circumstances is an example of "action at a distance" in the nervous system, and reminds clinicians to think broadly about the various pathophysiologic mechanisms that can potentially underlie common disorders(10). Other researchers suggested Trigeminal neuralgia (TN) is occasionally caused by cerebellopontine angle (CPA) tumors. Among 243 patients presenting with TN who had been operated on in our institute, 25 (10.3%) were caused by CPA tumors, which consisted of 11 epidermoid, 9 acoustic tumors, and 5 meningiomas. Cases with TN caused by tumors were clinically investigated in comparison with those of idiopathic TN.(11)


10. Hypertension
In the study of A total of 138,492 persons with at least 2 ambulatory visits with the principal diagnosis of hypertension in 2001 were enrolled in the hypertension group. The nonhypertension group consisted of 276,984 age- and sex-matched, randomly sampled subjects without hypertension, showed that a significantly increased risk of developing TN after hypertension. Further studies are needed to elucidate the underlying mechanism of the association between hypertension and TN(12). 


11. Other causes
Neuropathic pain refers to pain that originates from pathology of the nervous system. Common causes of neuropathic pain are diabetes mellitus, reactivation of herpes zoster, nerve compression or radiculopathy, alcohol, chemotherapy or abuse of some drugs, and trigeminal neuralgia(13).

12. Etc.

B. Risk factors
1. Age, sex and migraine
In the study conducted by  University of Rochester School of Medicine and Dentistry showed that Univariate and multivariate analyses indicated that older age, female sex, presence of a prodrome, greater rash severity, and greater acute pain severity made independent contributions to identifying which patients developed PHN. Patients with subacute herpetic neuralgia who did not develop PHN were significantly younger and had less severe acute pain than postherpetic neuralgia (PHN) patients but were significantly more likely to have severe and widespread rash than patients without persisting pain.(14). Other indicated that indicate that patients with migraine(M) should also be screened for symptoms of occipital neuralgia (ON), as there may be similarities in presentation. The clinical implications of distinguishing ON + M and isolated ON include differences in treatment regimen, avoidance of inappropriate use of medical resources, and differences in long-term outcomes.(15)

2. Immunity
In a report of 821 cases of herpes zoster that met all eligibility criteria, indicated that the prevalence of postherpetic neuralgia (PHN) more than 30 days after onset of zoster was 8.0% (95% confidence interval [CI], 6.3%-10.1%) and 4.5% (95% CI, 3.2%-6.2%) after 60 days. Compared with patients younger than 50 years, individuals aged 50 years or older had a 14.7-fold higher prevalence (95% CI, 6.8-32.0) 30 days and a 27.4-fold higher prevalence (95% CI, 8.8-85.4) 60 days after developing zoster. Prodromal sensory symptoms and certain conditions associated with compromised immunity were also associated with PHN. Systemic corticosteroids before zoster and treatment of zoster with acyclovir or corticosteroids did not significantly affect the prevalence of PHN.(16)

3. Nutrient deficiency
In the study to compare the nutritional status of PHN patients with that of healthy controls, and then to identify risk factors for PHN using multivariate multiple logistic regressions, conducted by Chi Mei Medical Center,, Dr. Chen JY and the medical team showed that lower concentrations of circulating nutrients, namely vitamin C, ionised Ca or Zn, are probably a risk factor in Taiwanese patients with PHN.(17)

4. Etc.

III. Diagnosis
Diagnosis of neuralgia is difficult, and misdiagnosis is common. Assessment of the patient with suspected neuropathic pain should focus on ruling out treatable conditions (e.g., spinal cord compression, neoplasm), confirming the diagnosis of neuropathic pain and identifying clinical features (e.g., insomnia, autonomic neuropathy) that might help individualize treatment. Box 1 lists principal details of the clinical evaluation, including history, physical examination and special tests.Diagnosis typically involves locating the damaged nerve by stimulation of the specific damaged pathway or by identifying missing sensory function(18)


IV. Preventions
A. The Do's and Do not's list 
1. Reduce unhealthy fat and increase intake of n-3 series polyunsaturated fatty acids
Both basic and clinical studies have shown that a dietary intake of n-3 series polyunsaturated fatty acids results in a reduction in the pain associated with rheumatoid arthritis, dysmenorrhea, inflammatory bowl disease, and neuropathy, Dr Tokuyama S and Dr. Nakamoto K. at the Kobe Gakuin University indicated(19).


2. Avoid infection
The best way to avoid infection caused by bacteria and virus is to enhance the immune system, people with weakened immune system such as chronic illness, aging, etc. are at increased risk infectious causes of neuralgia. There are suggestion that Innate immune cells play a central role in inflammation and are thus critical for the pathogenesis of inflammatory diseases(20)

3. Eating healthy with balance diet
Preferred eating certain kinds of food cam increase the risk of nutrients deficiency of that can trigger  Neuralgia  as we mention in (B.3.)


4. Moderate drinking
Excessive alcohol drinking can cause Neuralgia. Three cases of jaw pain recurrently precipitated by consumption of alcohol are described. Alcohol-induced neuralgia is added to the differential diagnosis of atypical orofacial pain(21).


5. Smoking
Dr. Parruti G and the team at the Infectious Disease Unit, Pescara General Hospital showed in one of the study that Smoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden(22)


6. Eat your fruits and vegetables
Fruits and vegetables contain high amounts antioxidants which can enhance the immune system in fighting against the forming of free radicals and foreign invasion such as viral and bacterial causes of infection.


7.  Etc.


B. Diet against neuralgia
1. Low fat diet
There are many articles which can easily found in the net indicated that low fat diet can stop TN PAIN, from the Presented at the Trigeminal Neuralgia Association's 5th National Conference with no author indicated, tittle " A LOW SATURATED FAT DIET STOPS TN PAIN" , the writer wrote that The 76 year old patient that was in constant pain, had an attack of colitis and while hospitalized was given no food only liquid.  After leaving the hospital she was put on a diet of liquid, bullion cube soup, and Jell-O.  In a week her pain stopped.  When she returned to her usual diet the pain returned.  I encouraged the patient to try the American Heart Association diet, and once again her pain was gone.  The patient was still taking 1200 mg of Tegretol daily.  However, when she reduced the saturated fat to10 grams a day, she was able to stop taking the Tegretol.  It is now six years later and the patient is still pain-free.(23)

2. Salmon
a. Antioxidants
In the research of the antioxidant effect of vitamin E after ingestion of salmon found that that megadoses of vitamin E, far from having pro-oxidative activity, actually increase the anti-oxidative capacity of the liver, especially after ingestion of salmon oil, according to "Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed lard or salmon oil" by Flader D, Brandsch C, Hirche F, Eder K.(24)

b.  Omega 3 fatty acids
Omega 3 fatty acids is necessary to maintain the ratio of good and bad cholesterol, thus reducing the risk of cholesterol inflammation according to the study of "In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation" by Wang S, Wu D, Lamon-Fava S, Matthan NR, Honda KL, Lichtenstein AH., posted in PubMed (IV) and forming of free radical in the heart cells, leading to heart diseases. It also reduces the risk of plaque forming in the arterial wall, thus also decreasing the risk of stoke, according to the study of "N-3 vs. saturated fatty acids: effects on the arterial wall" by Sudheendran S, Chang CC, Deckelbaum RJ., posted in PubMed (25).

3.  Green Tea
a. Immune system
In the investigation of the immunomodulatory effects of decaffeinated green tea extract in rain bow of the study of "Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK.[14a], researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout(26).

b. Antimicrobial activities
In the investigation of Antimicrobial activities of green of the study of "Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus" by Friedman M, Henika PR, Levin CE, Mandrell RE, Kozukue N.[13a], researchers found that flavonoids in green tea has exerted its ability in protective effects against Bacillus cereus(27)

4. Turkey
a. Selenium
Turkey contains trace minerals selenium which is essential for the healthy function of the thyroid and immune system as it increases the antioxidant defense system by fighting against the forming of free radicals and reduce the risk of irregular cells growth causes of tumor and cancer, according to the study of "Selenium in the immune system" by Arthur JR, McKenzie RC, Beckett GJ.(28)

b. Saturated fat ( It is essential but do not over dose)
Nerve and brain tissue is made up of 60% fat. One-third of these fats need to be polyunsaturated, derived directly from diet and other from cholesterol stored in our body. This will allow proper development and maintenance of nerve cell membranes as well as neurotransmitters in transformation between themselves and glands, according to the article of "Fat" by wikipedia.(29)

5. Flaxseed
a. Omega 3 fatty acidsBesides well known for its benefits for the maintenance of a healthy cardio-vascular system, according to the study of "Omega-3 Fatty acids for cardiovascular disease prevention" by Defilippis AP, Blaha MJ, Jacobson TA, posted in PubMed(I) and proper ratio of Omega 3 and 6 fatty acid and prevent blood clotting, it also extends the portion of your cycle in which you are fertile, by promoting natural ovulation, according tothe study of "Postpartum ovarian activity in multiparous Holstein cows treated with bovine somatotropin and fed n-3 fatty acids in early lactation" by Carriquiry M, Dahlen CR, Weber WJ, Lamb GC, Crooker BA., posted in pubMed (30)

b. Antioxidants
Flax seed contains a high amount of antioxidant that helps to guard the body from forming of free radicals by promoting the proper DNA replication and cells division, according to "Free radicals, metals and antioxidants in oxidative stress-induced cancer" by Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M.(31)

6. Orange
a. Bioavailability and antioxidant effects
In the reserach of Bioavailability and antioxidant effects of orange juice (OJ) into habitual diet found that after the 3 week intervention, plasma concentrations of vitamins A and E did not change. 8-Hydroxydeoxyguanosine in white blood cells declined by 16% (p = 0.38; n = 11), and in individuals with high baseline concentrations by 29% (p = 0.36; n = 7), respectively. Low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol ratios decreased but cholesterol (HDL, LDL, total) and thiobarbituric acid reactive substance plasma concentrations did not change significantly, according to "Bioavailability and antioxidant effects of orange juice components in humans?" by Franke AA, Cooney RV, Henning SM, Custer LJ.(32)

b. Antiplasmodial activity
In the assessment of plant extracts against Plasmodium falciparum. In the present study, the hexane, chloroform, ethyl acetate, acetone, and methanol extracts of Citrus sinensis (peel), Leucas aspera, Ocimum sanctum, Phyllanthus acidus (leaf), Terminalia chebula (seed) and theirs effect against Plasmodium falciparum found that components present in the solvent extracts of L. aspera, P. acidus, and T. chebula have antiplasmodial activity. The high antiplasmodial activity observed make these plants good candidates for isolation of anti-protozoal compounds which could serve as new lead structures for drug development, according to "Antiplasmodial activity of botanical extracts against Plasmodium falciparum" by Bagavan A, Rahuman AA, Kamaraj C, Kaushik NK, Mohanakrishnan D, Sahal D.(33)

c. Vitamin C
Vitamin C is considered as on of most powerful free radical scavenger, it helps to enhane the immune system fighting against forming of free radical cause of irregular cells growth due to mutation of cells' DNA, including tumors and cancers, according to the study of "Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later?" by Cabanillas F.(34)

7. Papaya
a. Anti-tumor activity and immunomodulatory effects
In the investigation of extract of Carica papaya Linn. (CP) and its anti-tumor activity and immunomodulatory effects found that the CP leaf extract may potentially provide the means for the treatment and prevention of selected human diseases such as cancer, various allergic disorders, and may also serve as immunoadjuvant for vaccine therapy, according to "Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects" by Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C.(35)

b. Anti-inflammatory activities
In the assessment of ethanolic extract of Carica papaya leaves and its anti-inflammatory activity effect found that the extracts significantly reduced the persistent oedema from the 4th day to the 10th day of the investigation. The extracts also produced slight mucosal irritation at high doses. The study establishes the anti-inflammatory activity of Carica papaya leaves, according to "Anti-inflammatory activities of ethanolic extract of Carica papaya leaves" by Owoyele BV, Adebukola OM, Funmilayo AA, Soladoye AO.(36)



c. Antioxidants
Vitamin C is considered as one of powerful free radical scavenger among vitamin by fighting against the lipidperoxidation and preventing the irregular growth of cancers, including breast cancer, according to the study of "Effect of vitamin C on lipidperoxidation and antioxidant status in tamoxifen-treated breast cancer patients" ralikrishnan G, Amanullah S, Basha MI, Boopalan S, Vijayakumar S, Shakeel F (37)


8. Onions
a. Antioxidant and anti-apoptotic effects
In the research of onion (Allium cepa) (ACE) extracts onion (Allium cepa) extracts and theirs antioxidant and anti-apoptotic effects found that the biochemical and histological disturbances were effectively attenuated on pretreatment with ACE. The present study showed that ACE may be a suitable cardioprotector against toxic effects of (DOX) doxorubicin, according to "Antioxidant and anti-apoptotic effects of onion (Allium cepa) extract on doxorubicin-induced cardiotoxicity in rats" by Alpsoy S, Aktas C, Uygur R, Topcu B, Kanter M, Erboga M, Karakaya O, Gedikbasi A.(38)


b. Anti-inflammatory

Since it contains high amount of antioxidants, onion enhances the immune system in fighting against the forming of free radicals and foreign invasion, thus eeducing the symptoms of inflammatory conditions such as arthritis and gout and infection caused by bacteria, including E.coli and salmonella,etc., according to the study of Antibacterial and antioxidant activities of quercetin oxidation products from yellow onion (Allium cepa) skin." by Ramos FA, Takaishi Y, Shirotori M, Kawaguchi Y, Tsuchiya K, Shibata H, Higuti T, Tadokoro T, Takeuchi M., posted in PubMed (39)

9. Cauliflower

a. Antioxidant capacity
In the classification of polyphenols, flavonoids and glucosinolates of vegetables belonging to the Brassicaceae family and theirs antioxidant effects found that the antibacterial activity was determined against Gram-positive and Gram-negative bacteria. York cabbage extract exhibited significantly higher antibacterial activity against Listeria monocytogenes (100%) and Salmonella abony (94.3%), being the most susceptible at a concentration of 2.8%, whereas broccoli, Brussels sprouts and white cabbage had moderate to weak activity against all the test organisms. Good correlation (r2 0.97) was found between total phenolic content obtained by spectrophotometric analysis and the sum of the individual polyphenols monitored by HPLC-DAD, according to "Phenolic composition, antioxidant capacity and antibacterial activity of selected Irish Brassica vegetables" by Jaiswal AK, Rajauria G, Abu-Ghannam N, Gupta S.(40)

b. Anti inflamatory effect
In the research of Benzyl isothiocyanate (BITC) found abundantly in Brassica vegetables and it anti inflammatory effect found that lipopolysaccharide (LPS)-stimulated phosphorylation of extracellular signal regulated kinase (ERK)1/2 and Akt was suppressed by BITC. BITC also inhibited ear edema formation and the protein expression of iNOS and COX-2 in mouse skin treated with TPA. We demonstrate that BITC is a potent anti-inflammatory agent, and the anti-inflammatory properties of BITC may result from the downregulation of NFkappaB signaling, according to "Benzyl isothiocyanate exhibits anti-inflammatory effects in murine macrophages and in mouse skin" by Lee YM, Seon MR, Cho HJ, Kim JS, Park JH.(41)

10. Etc.

C. Antioxidant against neuralgia(42)
1. Copper
Copper, an essential trace element is essential for the absorption and utilization of iron and distributed widely in the body and occurs in liver, muscle and bone. Deficiency of copper can often cause the anemia-like symptoms. However, ingesting too much of it can lead to generator of free radicals that can damage DNA
1.1. Antimicrobial and viral 
 Copper enhances the immune function in fighting against foreign invasion, such as bacteria and virus, thus reducing the risk of infection and inflammation by utilizing the absorption of oxygen and production of energy within cells. 
1.2. Antioxidant enzyme Superoxide dismutase (SOD)
Copper is vital for the making of antioxidant enzyme, superoxide dismutase, an important antioxidant defense in nearly all cells exposed to oxygen by protecting the cell membranes from free radicals. In fact, it outcompetes damaging reactions of superoxide, thus protecting the cell from superoxide toxicity. Research found in experiment, Mice lacking SOD1(Superoxide dismutase [Cu-Zn]) develop a wide range of pathologies, including hepatocellular carcinoma, an acceleration of age-related muscle mass loss,an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3(Extracellular superoxide dismutase [Cu-Zn] ) do not show any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic injury and mice lacking SOD2 (Superoxide dismutase 2, mitochondrial) die before birth. The above result enhances the importance of the presence of copper in improving life span and living health in human as well.

2. glutathione (GSH)
Glutathione (GSH), a polypeptide of glycine, cysteine, and glutamic acid that occurs widely in plant and animal tissues beside is best known for its role in enhancing the immune system in protect our body from bacteria and virus, it also is an antioxidant that helps to prevent damage caused by oxidation of cellular components such as free radicals and peroxides by converting to its oxidized form glutathione disulfide (GSSG), leading to generation of antioxidant enzymes, glutathione peroxidases and peroxiredoxins of which reduces the risk of oxidative DNA damage and subsequently the individual’s risk of cancer susceptibility.Deficiency of Glutathione (GSH) causes hemolytic anemia, progressive degeneration of the spinal cord, disorders of the peripheral nervous system, diseases of the skeletal muscles, etc. Intake with vitamin D increases glutathione levels in the brain and appears to be a catalyst for glutathione production.

3. Alpha lipoic acid
Alpha Lipoic Acid (ALA) is an organosulfur compound derived from octanoic acid. It has been used as over-the-counter nutritional supplements to treat a number of diseases and conditions. Alpha Lipoic Acid (ALA) not only is importance in preventing the symptoms of vitamin C and vitamin E deficiency, but also generates dihydrolipoic acid by reduction of antioxidant radicals. Recent study showed that Alpha lipoic acid may have a therapeutic and anti-aging effects due to modulation of signal transduction and gene transcription, which improve the antioxidant status of the cell.

4. Manganese
Manganese is an essential trace nutrient in all forms of life. It is well known for its role in helping the body to maintain healthy skin and bone structure, but also acts as cofactors for a number of enzymes in higher organisms, where they are essential in detoxification of superoxide (O2−, with one unpaired electron) free radicals. Although superoxide is biologically quite toxic and is deployed by the immune system to kill invading microorganisms by utilizing the enzyme NADPH oxidase. Any Mutations in the gene coding for the NADPH oxidase cause an immunodeficiency syndrome. Superoxide may contribute to aging via the oxidative damage that it inflicts on cells. In larger amounts, manganese can be poisoning to neurological damage which is sometimes irreversible.

5. Selenium
Selenium , a trace mineral plays an important and indirect role as an antioxidant by fulfilling its function as a necessary constituent of glutathione peroxidase and in production of glutathione, that inhibits the damage caused by oxidation of free radical hydrogen peroxide, leading to aging effects.
5.1. Heart health
Since it works synergism with vitamin E, it promotes heart health. Study showed by increasing the levels of glutathion, selenium decreases the risk of LDL oxidation, thus lowering the risk of plaque building up on the arterial walls, blood pressure and heart diseases.
5.2. Immune system
Selenium enhances the immune function that fighting off the attack of AID virus by promoting the function of interleukin 2 and T-cells.
5.3. Cancer
Study showed that levels pf selenium in blood test is associated with high rate of cancer, including skin cancer.

6. Zinc
Zinc is an essential mineral that is naturally present in some foods. The ability of zinc ininhibiting oxidative processes has been recognized for many years. Chronic effects, zinc enhances the introduction of metallothioneins, which help to capture the superoxide and hydroxyl radicals due to cysteine residues, resulting in lessening the risk of oxidative stress.
Over acute effects, zinc may reduce the postischemic injury to a variety of tissues and organs by involving the antagonism of copper reactivity as a result from its antioxidant functions.

7. Etc.

D. Phytochemicals against neuralgia
1. Rosemarinol, is a phytochemical monophenols, found in essential oil of labiate herbs like Rosemary and also in variety of other plants.
a. Drug-resistant infections, Anti-bacterial and fungal activities
In the investigation of the antimicrobial activity potential of the essential oil of rosemary and its drug-resistant mutants of Mycobacterium smegmatis effect found that characterization and isolation of the active compound(s) from the rosemary oil may be useful in counteracting gram-positive bacterial, fungal, and drug-resistant infections., according to "Potential of rosemary oil to be used in drug-resistant infections" by Luqman S, Dwivedi GR, Darokar MP, Kalra A, Khanuja SP.

b. Antimicrobial activity
In the observation of the essential oils from clove (Syzygium aromaticum (L.) Merr. et Perry) and rosemary (Rosmarinus officinalis L.) and their anti,icrobial effects found that The antimicrobial activity of combinations of the two essential oils indicated their additive, synergistic or antagonistic effects against individual microorganism tests. The time-kill curves of clove and rosemary essential oils towards three strains showed clearly bactericidal and fungicidal processes of (1)/(2) x MIC, MIC, MBC and 2 x MIC, according to "Antimicrobial activity of clove and rosemary essential oils alone and in combination" by Fu Y, Zu Y, Chen L, Shi X, Wang Z, Sun S, Efferth T.(43)

c. Anti-inflammatory effects
In the research of the extract of rosemary leaves from supercritical fluid extraction and its anti inflammatory effects found that the yield of 3.92% and total phenolics of 213.5 mg/g extract obtained from the most effective extraction conditions showed a high inhibitory effect on lipid peroxidation (IC(50) 33.4 μg/mL). Both the SC-CO(2) extract and CA markedly suppressed the LPS-induced production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), phosphorylated inhibitor-kappaB (P-IκB), and nuclear factor-kappaB (NF-κB)/p65 in a dose-dependent manner, according to the study of "Anti-inflammatory effects of supercritical carbon dioxide extract and its isolated carnosic acid from Rosmarinus officinalis leaves" by Kuo CF, Su JD, Chiu CH, Peng CC, Chang CH, Sung TY, Huang SH, Lee WC, Chyau CC.(44)

2.  Silybin is aslo known as Silibinin (INN), the major active ingredient of silymarin, a flavanone, found in the milk thistle seeds.
a. Antioxidants in vascular calcification
In the identification of natural antioxidants in the process of vascular calcification found that
Curcumin and silybin were the more effective, inhibiting both reactive oxygen species (ROS) increase and muscle cells (VSMCs) mineralization, according to "Natural antioxidants and vascular calcification: a possible benefit" by Roman-Garcia P, Barrio-Vazquez S, Fernandez-Martin JL, Ruiz-Torres MP, Cannata-Andia JB.(45)

b.  Anti-inflammatory effects
In the evaluation of Silymarin, derived from milk thistle (Silybum marianum). Milk thistle and its anti inflammatory effect in chronic hepatitis C patient found that Silymarin exerts anti-inflammatory and antiviral effects, and suggest that complementary and alternative medicine-based approaches may assist in the management of patients with chronic hepatitis C, according to "Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin" by Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DY.(46)

3. Tangeritin, one of the flavones, is found in tangerine and many citrus peels
a. Antioxidants
In the comparison of hand-pressed juice of polymethoxylated flavones (PMFs) and flavanone glycosides (FGs) and the peeled fruit of 'Sainampueng' tangerines ( Citrus reticulata Blanco cv. Sainampueng) antioxidant effects found that hand-pressed juice of C. reticulata Blanco cv. Sainampueng serves as a rich source of PMFs, FGs, carotenoids, and antioxidants: 4-5 tangerine fruits ( approximately 80 g of each fruit) giving one glass of 200 mL hand-pressed juice would provide more than 5 mg of nobiletin and tangeretin and 36 mg of hesperidin, narirutin, and didymin, as well as 30 mg of ascorbic acid, >1 mg of provitamin A active beta-cryptoxanthin, and 200 microg of alpha-tocopherol, according to "Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines ( Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand" by Stuetz W, Prapamontol T, Hongsibsong S, Biesalski HK.(47)

b. Antimicrobial activity
In the study of antibacterial and antifungal properties of wax and hexane extracts of Citrus spp. peels found that antimicrobial activity especially against M. canis and T. mentagrophytes: 4',5,6,7,8-pentamethoxyflavone (tangeritin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) from C. reticulata; and 6,7-dimethoxycoumarin (also known as escoparone, scoparone or scoparin) from C. limon, according to "Antimicrobial activity of wax and hexane extracts from Citrus spp. peels" by Johann S, Oliveira VL, Pizzolatti MG, Schripsema J, Braz-Filho R, Branco A, Smânia Jr A.(48)

4. Theaflavin with reddish in color, is a phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), formed in tea leaves during fermentation.
a. Anti-oxidant, anti-inflammatory, and anti-apoptotic activities
In the investigation of the role of theaflavin, a polyphenol substance extracted from black tea, in attenuating acute I/R injury in a fatty liver model, found that theaflavin significantly diminished the ROS production of steatotic hepatocytes and TNF-α production by LPS-stimulated RAW264.7 cells and concluded that theaflavin has protective effects against I/R injury in fatty livers by anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms, according to "Theaflavin attenuates ischemia-reperfusion injury in a mouse fatty liver model" by Luo XY, Takahara T, Hou J, Kawai K, Sugiyama T, Tsukada K, Takemoto M, Takeuchi M, Zhong L, Li XK.(49)

b. HIV-1 infection
In the investigation of the mechanism by which TFmix inhibits HIV-1 infection was investigated using time-of-addition, found that TFmix is an economic natural product preparation containing high content of theaflavins with potent anti-HIV-1 activity by targeting the viral entry step through the disruption of gp41 6-HB core structure. It has a potential to be developed as a safe and affordable topical microbicide for preventing sexual transmission of HIV, according to "A natural theaflavins preparation inhibits HIV-1 infection by targeting the entry step: Potential applications for preventing HIV-1 infection" by Yang J, Li L, Tan S, Jin H, Qiu J, Mao Q, Li R, Xia C, Jiang ZH, Jiang S, Liu S.(50)

5. Genistein is a phytochemical in the Isoflavones, belonging to the group of Flavonoids (polyphenols), found abundantly in food of the family of legumes, soy, alfalfa sprouts, red clover, chickpeas, peanuts, etc.

a.  Immunomodulation And Anti-Inflammation
In the review of new concepts have emerged in relation to mechanisms that contribute to the regulation of carcinogenesis processes and associated inflammatory effects, found that the effects of polyphenols on the adaptative and innate immune cells that could infiltrate the tumor. Reduction of chronic inflammation or its downstream consequences may represent a key mechanism in the fight of cancer development and polyphenols could reduce various pro-inflammatory substance productions through targeting signal transduction or through antioxidant effects, according to "Immunomodulation And Anti-Inflammatory Roles Of Polyphenols As Anticancer Agents" by Ghiringhelli F, Rébé C, Hichami A, Delmas D.(51)

b.  Antioxidant effects
In the testing effects of the soy isoflavone genistein on antioxidant enzymes in DU145 prostate cancer cells, found that Genistein significantly decreased reactive oxygen species levels and induced the expression of the antioxidant enzymes manganese (Mn) superoxide dismutase (SOD) and catalase, which were associated with AMP-activated protein kinase (AMPK) and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathways. The induced expression of catalase, MnSOD, and PTEN were attenuated by pretreatment with a pharmacological inhibitor for AMPK. Furthermore, PTEN is essential for genistein activity, as shown by PTEN transfection in PTEN-deficient PC3 cells. Thus, genistein induces antioxidant enzymes through AMPK activation and increased PTEN expression. indicating the effects of genistein primarily depend on AMPK, according to "The antioxidant effects of genistein are associated with AMP-activated protein kinase activation and PTEN induction in prostate cancer cells" by Park CE, Yun H, Lee EB, Min BI, Bae H, Choe W, Kang I, Kim SS, Ha J.(52)

6. Coumestrol, a phytoestrogen in the class of coumestans, belonging to the group of Flavonoids (polyphenols) found abundantly in red clover, alfalfa sprouts, soy, peas, brussels sprouts, etc.

a. Anti-inflammatory activities
In the investigation of A new coumestan (solalyratin A, 1) and a novel cyclic eight-membered α,β-unsaturated ketone (solalyratin B, 3), together with three known compounds, puerariafuran (2), coumestrol (4) and 9-hydroxy-2',2'-dimethylpyrano[5',6':2,3]-coumestan (5), isolated from the whole plant of Solanum lyratum, found that in vitro, compounds 1-5 showed anti-inflammatory activities, with IC(50) values in the range 6.3-9.1 μM, according to "Solalyratins A and B, new anti-inflammatory metabolites from Solanum lyratum" by Zhang DW, Yang Y, Yao F, Yu QY, Dai SJ.(53)

b. Antimicrobial activity
in the determination of the effects of the isoflavonoids coumestrol, genistein and daidzein isolated and identified by bioassay-guided fractionation from the acetone extract of Erythrina crista galli young twigs infected with Phomopsis sp, found that these compounds showed antimicrobial activity against Bacillus brevis (MIC values 16.3, 64.8 and 137.8 microM, respectively), according to "Antimicrobial isoflavonoids from Erythrina crista galli infected with Phomopsis sp" by Redko F, Clavin ML, Weber D, Ranea F, Anke T, Martino V.(54)

7. Turmeric, principal curcuminoid of the popular Indian spice, a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae, native to tropical South Asia, according to "Effects of different drying methods on the antioxidant properties of leaves and tea of ginger species" by E.W.C. Chan, Y.Y. Lim, S.K. Wong, K.K. Lim, S.P. Tan, F.S. Lianto and M.Y. Yong, posted in Science Direct. It has been used in traditional herbal medicine as an anti-inflammatory agent and to treat gastrointestinal symptoms associated with irritable bowel syndrome and other digestive disorders. Curcumin is a phytochemical found abundant in the plant. In acidic solutions (pH <7.4) it turns yellow, whereas in basic (pH > 8.6) solutions it turns bright red.

a. Anti-inflammatory agent
According to the study of evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. by Satoskar RR, Shah SJ, Shenoy SG., poated in US National Library of Medicine National Institutes of Health, researchers wrote that In this model of postoperative inflammation, the anti-inflammatory activity of curcumin (diferuloyl methane) was investigated in comparison with phenylbutazone and placebo. Phenylbutazone and curcumin produced a better anti-inflammatory response than placebo.

b. Antioxidants
In a study of `Protective Role of Curcumin Against Oxidative Stress,Immunosuppressive and Cytotoxic Effects of Lead Exposure` by Mahmoud El-sherbiny, Azza Araffa, Mona Mantawy and Hany M. Hassan (Therapeutic Chemistry Department, National Research Centre - Dokki, Giza, Egypt. Immunology Department, Animal Reproduction Research Institute (ARRI), Giza, Egypt), posted in World Applied Sciences Journal 12 (10): 1832-1838, 2011, researchers found that ground, curcumin's benefits on tumorigenesis are thought to be mediated by its antiinflammatory activity; however, these effects have not been well characterized in a mouse model of colon cancer. Briefly, curcumin is efficacious for chronic nonbacterial prostatitis in rats and the action mechanism may be associated with its decreasing effect on the proinflammatory cytokines IL-8 and TNF-alpha in the blood and tissues. Curcumin has protective effect on DNA of pulmonary cells. There was direct evidence for an involvement of curcumin in reducing arsenic and lead induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals. The current investigation concluded that curcumin has protective role against cytotoxic, immunosuppressive , oxidative and immunosuppressive profile that perform due to lead acetate exposure.

8. Etc.

V. Treatments

A. In conventional medicine perspective
A.1. Medical treatment
Dr. Masudai. in the study of Diagnosis and treatment of trigeminal neuralgia suggested  "Trigeminal neuralgia is a disease affecting older individuals. The clinical hallmark of trigeminal neuralgia is a sudden, excruciating paroxysm of pain in the area of the trigeminal nerve. Drug therapy is considered the first line of treatment for trigeminal neuralgia. Anticonvulsant carbamazepine has been used. If relevant pharmacotherapy has been tried without any effect, other procedures are selected. These procedures are microvascular decompression(a radical technique), glycerol trigeminal rhizotomy, percutaneous trigeminal nerve decompression and nerve block. Nerve block with neurolytic solutions and radiofrequency thermocoagulation is a simple, less invasive therapy. In order to avoid hypesthesia and dysesthesia, nerve block using a high concentration of local anesthetics is recommended. In recent years, stereotactic radiosurgery for trigeminal neuralgia has emerged as a new therapeutic modality(55)

Other suggested that First-line treatments for PHN include tricyclic antidepressants, gabapentin and pregabalin, and the topical lidocaine 5% patch. Opioids, tramadol, capsaicin cream, and the capsaicin 8% patch are recommended as either second- or third-line therapies in different guidelines. Therapies that have demonstrated effectiveness for other types of neuropathic pain are discussed, such as serotonin-norepinephrine reuptake inhibitors, the anticonvulsants carbamazepine and valproic acid, and botulinum toxin. Invasive procedures such as sympathetic blockade, intrathecal steroids, and implantable spinal cord stimulators have been studied for relief of PHN, mainly in patients refractory to noninvasive pharmacologic interventions. The main guidelines considered here are those issued by the American Academy of Neurology for the treatment of postherpetic neuralgia (2004) and general guidelines for the treatment of neuropathic pain issued by the Special Interest Group on Neuropathic Pain of the International Association for the Study of Pain (2007) and the European Federation of Neurological Societies (2010)(56)

B.2. Non Medication Treatment 
1. Exercise
Regular moderate aerobic exercise reversed signs of neuropathic pain and increased endogenous opioid content in brainstem regions important in pain modulation. Exercise effects were reversed by opioid receptor antagonists. These results suggest that exercise-induced reversal of neuropathic pain results from an up-regulation of endogenous opioids(57). 

2. Transcutaneous electrical nerve stimulation
Dr. Yameen F and the team at the Dow University of Health Sciences and Civil Hospital suhested that Out of 31 patients, 20 females and 11 males, with a mean age of 50.1 +/- 11 years, 26 (83.7%) improved significantly with application of TENS, only 5 (16.3%) patients remained unresponsive to this form of therapy. Study also showed a better efficacy of constant mode of therapy over burst mode. Transcutaneous electrical nerve stimulation is an effective, easy to use therapy with minimal side effects in patients suffering from trigeminal neuralgia not responding to conventional treatment(58).

3. Percutaneous electrical nerve stimulation
The study conducted by Dasmesh Institute of Research and Dental Sciences, showed that on visual analogue scale (VAS), the score decreased from 8.9 (Pre Transcutaneous electric nerve stimulation (TENS)) to 3.1 at 1 month and 1.3 at 3 months, and on verbal pain scale (VPS), the score decreased from 3.5 (Pre TENS) to 1.2 at 1 month and 0.3 at 3 months. Similarly, a considerable decrease in scores was seen on functional outcome scale for different activities. No side effects like irritation or redness of skin were seen in any of the patients(59).
 
4.  Graded motor imagery
Some reserachers suggested that Motor imagery reduced pain and disability in these patients with complex regional pain syndrome type I or phantom limb pain, but the mechanism, or mechanisms, of the effect are not clear(60).
 
5. Cognitive behavioural therapy
Fourteen studies were assessed: three randomized controlled trials, three controlled before-after studies, seven uncontrolled before-after studies and one time series analysis by Erasmus University Rotterdam, Dr, Wetering EJ, and the research team indicated that The findings of the meta-analysis were not consistent with a significant effect on pain intensity. Only one study had good methodological quality; it showed some significant effects of the interventions, but only in female participants. Other studies of limited methodological quality did report positive effects on pain and quality of life(61).


6. Etc.

B.3. Pharmacology is is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function(62).
In a study to investigate pharmacologically a rat model of trigeminal neuropathic pain: baclofen, but not carbamazepine, morphine or tricyclic antidepressants, attenuates the allodynia-like behaviour, Dr. Juhana J Idänpään-Heikkilä and Dr. Gisèle Guilbaud showed that Pharmacological studies indicated that the mechanical hyper-responsiveness could be reversibly abolished by local injections of alphacaine into the close proximity of the injured nerve. The allodynia-like behaviour was resistant to i.v. morphine. Similarly, single and repeated injections (using the respective T_1/2 as an interval) of tricyclic antidepressants amitriptyline and clomipramine were devoid of effects on the mechanical allodynia-like behaviour. Carbamazepine was effective only after doses (≥10 mg/kg s.c.) that already caused disturbances in motor co-ordination in the rotarod test. Repeated injections of baclofen (3 mg/kg s.c.) partially alleviated the mechanical allodynia-like behaviour without effects on rotarod performance. The partial anti-allodynic effect of a single injection (5 mg/kg) of baclofen, which was already accompanied by slight motor disturbances, could be antagonized by CGP35348, a selective GABA_B-receptor antagonist. Functional deficits in the GABAergic system may play an important role in the pathogenesis of this purely sensory rat model of trigeminal neuropathic pain(63).


B.4. Surgery
Surgical interventions are used for trigeminal neuralgia only when drug treatment fails. Dr. Joanna M Zakrzewska and Dr, Harith Akram said in the study of Neurosurgical interventions for the treatment of classical trigeminal neuralgia "There is very low quality evidence for the efficacy of most neurosurgical procedures for trigeminal neuralgia because of the poor quality of the trials. All procedures produced variable pain relief, but many resulted in sensory side effects. There were no studies of microvascular decompression which observational data suggests gives the longest pain relief. There is little evidence to help comparative decision making about the best surgical procedure. Well designed studies are urgently needed"(64)

B. In herbal medicine perspective
The aim of herbal medicine is to enhance the body immune system in fighting off the invasion of viral and bacterial causes of neuralgia.

1. Black Cohosh 
Black Cohosh is a herbaceous perennial plant, genus Actaea, belonging to the family Ranunculaceae, native to eastern North America. The herb has been used in traditional medicine as analgesic, sedative, diuretic, emmenagogue anti-inflammatory agent and to treat rheumatism, symptoms of menopause, uterine cramps and muscle pain, etc.. Native Americans have used the root of the herb to treat snake bite.
a. Antioxidants
Polyphenols in Black cohosh may be considered as an antioxidant which help to fight against the forming of free radicals cause of DNA damage and guarding our body against foreign invasion such as bacteria and virus, according to the study of "Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: bioassay-directed isolation and characterization of active principles" by Burdette JE, Chen SN, Lu ZZ, Xu H, White BE, Fabricant DS, Liu J, Fong HH, Farnsworth NR, Constantinou AI, Van Breemen RB, Pezzuto JM, Bolton JL., posted in PubMed(65)

b. Anti-inflammation
Cimicifuga racemosa (Actaea racemosa, black cohosh)have exerted inflammatory activity by inhibiting nitric oxide production by reducing iNOS expression without affecting activity of the enzyme, according to the study of "Inhibition of inducible nitric oxide synthesis by Cimicifuga racemosa (Actaea racemosa, black cohosh) extracts in LPS-stimulated RAW 264.7 macrophages" by Schmid D, Gruber M, Woehs F, Prinz S, Etzlstorfer B, Prucker C, Fuzzati N, Kopp B, Moeslinger T., posted in PubMed(66)

2. Peppermint
Peppermint is a hybrid mint with small purple or white flowers and downy leaves, in the genus Mentha, belonging to the family Lamiaceae, native to to Europe. The herb has been used in folk medicine as analgesic, antiseptic, antispasmodic, decongestant, agent and to relieve gas, nausea, and stomach pain due to an irritable bowel, intestinal cramps, or indigestion, infecttion, etc.
a. Antimicrobial and antioxidant activities
In the observation of the antimicrobial activity and free radical scavenging capacity (RSC) of essential oils from Mentha aquatica L., Mentha longifolia L., and Mentha piperita L., found that The M. piperita essential oil also exhibited the highest OH radical scavenging activity, reducing OH radical generation in the Fenton reaction by 24 % (pure oil). According to GC-MS and TLC (dot-blot techniques), the most powerful scavenging compounds were monoterpene ketones (menthone and isomenthone) in the essential oils of M. longifolia and M. piperita and 1,8-cineole in the oil of M. aquatica, according to "Antimicrobial and antioxidant activities of three Mentha species essential oils" by Mimica-Dukić N, Bozin B, Soković M, Mihajlović B, Matavulj M.(67)

b. Antispasmodic effect
In the investigation of Hyperperistalsis during upper gastrointestinal endoscopy
found that the effectiveness of peppermint oil administration to the gastric mucosa resulted in inhibiting the gastric peristalsis in Japanese individuals undergoing upper gastrointestinal endoscopy, according to "[Peppermint oil reduces gastric motility during the upper gastrointestinal endoscopy]. [Article in Japanese]" by Hiki N.(68)

c. Neurodegenerative diseases
In the analyzing the efficacy of peppermint oil in enhancing the bioavailability of intranasally administered neurotrophins like nerve growth factor (NGF), found that intranasal administration of NGF formulation with 0.5% PO enhanced the bioavailability by approximately 8 fold compared to rats administered with NGF alone. The bioavailability of NGF in the brain could be enhanced by intranasal administration of peppermint oil, according to 'Enhancement of nose-brain delivery of therapeutic agents for treating neurodegenerative diseases using peppermint oil" by Vaka SR, Murthy SN.(69)

3. Garlic
Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc.
a. Antifungal antitumor cytotoxicity and blood coagulability effects
In the identification of organosulfur compounds and theirs effects on cardiovascular diseases found that in vitro antifungal antitumor cytotoxicity and blood coagulability effects of steroid saponins from garlic and related Allium species are provided. Animal studies on the cholesterol-lowering effects of the saponin fractions from garlic are also summarized, according to "Saponins in garlic as modifiers of the risk of cardiovascular disease" by .Matsuura H(70)

b.  Antioxidant effects
In the study of the Extracts of aged fresh garlic that are aged over a prolonged period and its antioxidant effects found that the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease, according to "Antioxidant health effects of aged garlic extract" by

Borek C.(71)

4.  Muira Puama
Muira Puama is a flowering plants in the genus of Ptychopetalum in thefamily Olacaceae, native to the Amazon rainforest.The herb has been used in traditional medicine to enhance sexual desire, erectile function and to treat dysentery, rheumatism nervous tension, depression, etc.
a. Anti-stress effects
In the investigation of Marapuama (Ptychopetalum olacoides Bentham, PO and its anti-stress properties found that Ptychopetalum olacoides (Marapuama) might possess adaptogen-like properties, according to "Anti-stress effects of the "tonic"Ptychopetalum olacoides (Marapuama) in mice" by Piato AL, Detanico BC, Linck VM, Herrmann AP, Nunes DS, Elisabetsky E.(72)

b. Antioxidant activities
In the identification of of PO ethanol extract (POEE) free-radical scavenging properties in vitro, found that POEE administration reduced free-radical production in the hypothalamus, lead to significant decrease in lipid peroxidation in the cerebral cortex, striatum and hypothalamus, as well as in the carbonyl content in cerebellum and striatum. In terms of antioxidant enzymes, catalase activity was increased in the cortex, striatum, cerebellum and hippocampus, while glutathione peroxidase activity was increased in the hippocampus and concluded that POEE contains compounds able to improve the cellular antioxidant network efficacy in the brain, ultimately reducing the damage caused by oxidative stress, according to "Antioxidant activities of Ptychopetalum olacoides ("muirapuama") in mice brain" by Siqueira IR, Fochesatto C, Torres IL, da Silva AL, Nunes DS, Elisabetsky E, Netto CA.(73)


5. Parsley
Parsley (Petroselinum crispum) is a biennial flowering plant, genus Petroselinum, belonging to the family Apiaceae, native to the Mediterranean region of southern Europe. The herb has been used in traditional medicine as diuretic agent, and to release spasms, reduce inflammation, clear toxins, enhance the digestion and stimulate uterus, regulate menstrual cycle, treat edema, etc.
a. Antioxidants
In the investigation of Antioxidant activities of the total phenolics and HPLC analyses of the phenolic compounds of extracts from common Mediterranean plants, found that the antioxidant activities were evaluated according to the 2,2-diphenyl-1-picrylhydrazyl radical scavenger method. Sage (Salvia officinalis) showed the highest antioxidant activity (91%), while the lowest (11.3%) was seen in parsley (Petroselinum crispum). A strong correlation (r = 0.85) between antioxidant activity and total phenolic content was found, according to "Antioxidant activities, total phenolics and HPLC analyses of the phenolic compounds of extracts from common Mediterranean plants" by Rababah TM, Ereifej KI, Esoh RB, Al-u'datt MH, Alrababah MA, Yang W.(74)

b.  Immunomodulatory effect
In the determination of the suppressive effects of parsley essential oil on mouse splenocytes and macrophages cells, found that parsley essential oil may be able to suppress the cellular and humoral immune response. It can also suppress both NO production and the functions of macrophages as the main innate immune cells. These results may suggest that parsley essential oil is a proper suppressant for different applications, according to "Immunomodulatory effect of Parsley (Petroselinum crispum) essential oil on immune cells: Mitogen-activated splenocytes and peritoneal macrophages" by Yousofi A, Daneshmandi S, Soleimani N, Bagheri K, Karimi MH.(75)

c. Antimicrobial effects
In the study of the effect of cayenne, green pepper, parsley, and dill to Kareish cheese and to evaluate the antimicrobial activity of these plant materials against natural microflora, coliforms, molds, and Staphylococcus aureus, found that kareish cheese prepared with 1% cayenne pepper and 3% and 6% each of green pepper, dill, and parsley were found strongly acceptable to the consumer and considered the most preferable type. Therefore, this study revealed that pepper, parsley, and dill exhibited antibacterial activity against natural microflora, coliforms, yeast and molds, and S. aureus in Kareish cheese, and the addition of these plants is acceptable to the consumer and may contribute to the development of new and safe varieties of Kareish cheese, according to "Antimicrobial effects of pepper, parsley, and dill and their roles in the microbiological quality enhancement of traditional Egyptian Kareish cheese" by Wahba NM, Ahmed AS, Ebraheim ZZ.(76)


6. Etc.


C. In traditional Chinese medicine perspective 
The aim of traditional Chinese medicine is to improve all sysmptoms, prevent and treat later complications, correct imbalance, adjust the immune system and most importantly to boost energy and strong body for better health and quality of life. Hsin Kuang herbal store and clinic(77)
recommend a herbal combination o treat Intercostal neuralgia consisting of the following herbs and possibly others. Please consult with you TCM practinioner before using the formula, Kyle J. Norton notes
1. Fructus Meliae Toosendan 
 Bitter, Cold, Slightly Toxic  
2. Semen Sinapis Albae 
Acrid in flavor and warm  
3. Radix Clematidis
Pungent and salty in taste, warm in nature, and distributed to the Urinary Bladder Channel.  
4. Rhizoma Corydalis   
Pungent and bitter in taste and warm in nature, it is therapeutically related to the Channels of the Liver and Spleen.  
5. Radix Angelicae Sinensis   
The sweet and pungent in taste, warm in nature and therapeutically related to the channels of the Liver, Heart and Spleen.
6. Pollen Typhae  
Sweet; neutral  
7. Rhizoma Ligustici Chuanxiong 
 Pungent; warm  
8. Fructus Gardeniae     
Bitter to the taste, cold in nature, and distributed to the Heart, Lung and Tri-Jiao Channels.  
9. Radix Paeoniae Alba 
Bitter and sour in taste and slightly cold in nature, and is distributed to the Liver and Spleen Channels.  
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