International Journal of ISSN: 2381-1803IJCAM

Complementary & Alternative Medicine
Editorial
Volume 1 Issue 4 - 2015
Topical and Oral Herbal Pain Remedies
Eugene Zampieron* and Ellen Kamhi
University of Bridgeport College of Naturopathic Medicine, USA
Received:August 24, 2015 | Published: August 26, 2015
*Corresponding author: Eugene Zampieron, University of Bridgeport College of Naturopathic Medicine, 413 Grassy Hills Rd, Woodbury, CT 06798, USA, Tel: (203) 263-2970; Email:
Citation: Zampieron E, Kamhi E (2015) Topical and Oral Herbal Pain Remedies. Int J Complement Alt Med 1(4): 00021. DOI: 10.15406/ijcam.2015.01.00021

Editorial

The World Health Organization has proclaimed the years 2000-2010 the Decade of Joint Health, because joint health is such a widespread public health concern. Arthritis is a general term used to describe a large grouping of health conditions, all of which manifest symptoms of pain and stiffness. Commonly diagnosed forms of arthritis include osteoarthritis, rheumatoid arthritis (autoimmune involvement), gout, psoriatic arthritis, ankylosing spondylitis, fibromyalgia and infectious arthritis (such as Lyme’s Disease). The most prevalent debilitating forms are rheumatoid arthritis (RA), affecting 3 million people in the U.S., and the far more common osteoarthritis (OA),.Some estimate that as many as 40 million Americans suffer with osteoarthritis. The most commonly recognized causes of arthritis are genetic predisposition, advancing age, obesity, trauma and “wear and tear.” However, the ‘wear and tear’ theory is probably an oversimplification, because many elderly people never develop arthritis, after years of wear and tear [1]. The degeneration of joints in all types of arthritis involves ongoing biochemical processes that negatively alter metabolism essential to maintaining healthy joints. Although conventional medical diagnostics attempt to assign patients a differential diagnosis of one specific kind of arthritis, in reality, many patients exhibit a continuum of symptoms. For example, even in those individuals who are officially diagnosed with osteoarthritis, many pro-inflammatory cytokines are released. This may not be due to the immune dis-regulation associated with rheumatoid arthritis, but instead can be caused by a myriad of other factors, such as toxicity and high levels of oxidative stress, which lead to accelerated tissue destruction [2].

Pain Management

In natural medicine, the goal is to address the causative factors of illness through an examination of diet, lifestyle, allergies, toxic load, gut integrity, presence of microorganisms and psychological factors. Uncovering these factors, and making the behavioral changes that will positively affect the disease process, ultimately will lead to increased wellness. However, these steps take time, and the issue of pain management needs to be addressed immediately, while the body readjusts to a less inflammatory state. While pharmaceutical drugs offer effective pain relief, their use long term is not desirable due a large number adverse secondary effects. NSAIDs, in particular, actually make the overall disease process of arthritis worse, by increasing the destruction of the tight junctures in the gastrointestinal mucosa, commonly known as ‘leaky gut’ and by depleting the very nutrients necessary for joint repair, including iron [3], folic acid [4] and zinc [5]. COX 2 inhibitors, introduced with a media blitz touting them as a much safer drug therapy, are now known to also have serious side effects [6]. In this article, we will review several oral and topical botanical approaches to the pain and inflammation associated with arthritis, and other inflammatory conditions.

Topicals For Pain

For eons of time, humankind has searched for effective pain relief through the use of natural medicines applied topically over a painful or injured area. When some part of the body is injured, the innate, natural response is to rub the afflicted area. This act of rubbing itself seems to be therapeutic; however, the use of herbs when applied topically can enhance the healing response. Many botanicals offer excellent relief of pain and inflammation when massaged over muscles, tendons, ligaments and joints that are aching, tender, or traumatized.

Boswellia (Boswellia serrata)

Boswellia is a well researched herb that is a useful anti-inflammatory and can be used both internally and topically. For a full referenced discussion of Boswellia, please visit the section below in “Botanicals Taken Orally” below.

Teasel (Radix dipsacus)Xu Duan

Teasel is often referred to as Dipsacus. It is a dramatic tall flowering plant which has been used as a ‘comb’ both to groom animal and human hair and to pull wool on a weaving loom. It is commonly used in formulas for osteoarthritis in Traditional Chinese Medicine. Dipsacus tonifies the liver and kidneys, two of the organs most affected in arthritis. Dipsacus helps strengthen the bones and tendons and prevents damage from wear and tear. It also promotes the circulation of blood and helps “moisten” the joints. While research on Dipsacus as a solo herb is sparse in the medical literature, Dipsacus has shown clinical effectiveness in treating arthritis as part of TCM formulas such as Wangbi Chongji [7] and Shuguan Wenjing [8].

Angelica (Angelica pubescence, Angelica dahuricae)

The genus Angelica has many species which are traditionally used to assist in the moving of Qi and blood, eliminating blockages into the afflicted body part. Both topical and oral applications have demonstrated anti nociceptive action, thereby mitigating soreness and tenderness [9,10].

Rue (Ruta graveolens)

Ruta contains many anti-inflammatory flavonoids [11], which can inhibit inflammation and reduce oxidative damage related to arthritis and other inflammatory conditions [12]. Rue is particularly useful for ligaments and tight muscles following injuries. (i.e pulled hamstrings) It can be used topically or in homeopathic doses. Rue should not be used internally due to toxicity issues.

Aconite (Aconitum napellus)

The great healer Paracelsus has been quoted as saying… “Everything is poison…nothing is poison…only the dose permits something not to be poisonous. "Toxic substances may be harmless in small doses, while ordinarily harmless substances can be deadly if over-consumed: Even water !

Aconite, also referred to as Monkshood, is an herb feared by many due to its powerful effects and high degree of toxicity. However, in the proper small dose, it is unrivaled in its analgesic effects. Aconite first stimulates and later sedates nerves that are involved with pain, touch and temperature. The initial tingling gives way to a long continued anesthetic action. The famous Eclectic MD, Dr. Ellingwood, found that aconite could be extremely useful in the relief of acute pain. He suggested,… “perhaps the most immediate influence obtainable in acute pain is to put 5 drops each of Menthol and Aconite into the palm of the hand and hold it over the seat of pain for 2-3 minutes. The effect is instantaneous and marvelous.” One of the alkaloids found in Aconite, mesaconitine, shows efficacy in pain relief greater than can be achieved by the use of morphine [13]. However, the mechanism of action differs, since mesaconitine does not bind to opioid receptors, but via 5-HT receptors (5-hydroxytryptamine receptors) [14]. The 1968 Medicines Act recommends the use of aconite in topical preparations that does not exceed 1.3 parts of aconite to 100 parts of the topical applicant. This has been found to be below the amount that may cause a toxic reaction.

Bryonia (Bryonia alba)

The Eclectic medical doctors prominent in the late 1800’s and early 1900’s, recommended minute doses of bryonia as a remedy for arthritis. Indications for bryonia include:
1) Red or warm joints
2) Joint pain that is worse with exertion and better with resting or after applying
support such as a brace or ace bandage
3) Joint pain that is worse in cold wet weather, but improved by heat

Bryonia contains several bitter glycosides including bryonin, bryoamaride, bryoniosides A-G, bryodulcoside, cucurbitacins, dihydrocucurbitacins, bryoioside, cabenoside and chrysophanic acid [15].

Cayenne (Capsicum spp.)

The oleoresin, capsicum, is a resin found in many species of “hot peppers”. Shamans and folk healers traditionally used capsicum as a skin rub for pain. More recent scientific studies have proven that this action depletes “Substance P”, a chemical released in response to injury and inflammation, which is believed to be overabundant in the peripheral nerves of patients with arthritis, fibromyalgia and other painful syndromes.

Capsaicin binds to nociceptors in the skin, which stimulate afferent thinly-myelinated A and un-myelinated C nerve pain fibers. One of the main receptors is the Vanilloid Receptor 1 (VR1). VR1s are found in the peripheral neurons in the skin, specifically the A and C nerve fibers. Some VR1s are found in the brain, notably glutaminergic VRs exist in the hypothalamus where they are believed to be associated with the mediation of hypothermic actions [16,17]. VR1 is a non selective, cation channel which mediates stimuli from both chemical and physical triggers, including heat, low pH, capsaicin and chemical bi-products released due to inflammation. When the VR1 receptor is not activated it remains closed. Upon activation (ie. capsaicin binding), the VR1 channel opens. When capsaicin binds and the VR1 channel opens, a flood of calcium ions results in a depolarization of the nerve and an action potential. When the neurons containing these receptors are stimulated, they release the neurotransmitter, substance P. Substance P communicates a message perceived as an itch, burning sensation, or pain. If capsicum therapy is repeated often, the body cannot replenish substance P quickly enough to trigger the perception of pain. The depleted level of substance P results in analgesia for many types of pain: nociceptive pain (transmitted by normal physiologic pathways), neuropathic pain (due to diabetic neuropathy), shingles, post-amputation pain syndrome and trigeminal neuralgia [16,17]. In addition to the depletion of substance P, some researchers have discovered that on-going treatment with capsaicin results in an irreversible destruction of primary afferent terminals related to the peripheral nerves, leading to analgesia. If the capsicum treatment is discontinued, the nerves can regenerate, leading to a return of sensation and pain [18,19].

Ginger (Zingiber officinale)

Ginger is a medicinal plant that has been widely used in Chinese, Ayurvedic and Tibb- Unani herbal medicines all over the world since antiquity. It has applications for a wide array of unrelated ailments that include arthritis, rheumatism, sprains, muscular aches, pains, sore throats, cramps, constipation, indigestion, nausea, vomiting, hypertension, dementia, fever, infectious diseases and helminthiasis [20]. Ginger’s name is derived from an ancient Sanskrit name, ‘singabera’(grows like a horn), which closely describes the appearance of the ginger rhizome. Ginger contains zingerberol, gingerols, shogaols, bisabolene, borneol, zingabaine and capsaicin [21]. Ginger suppresses prostaglandin synthesis through the inhibition of cyclooxygenase-1 and cyclooxygenase-2, and suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase, as well as modulating the cytokine, NF-Kappa Beta. Dual inhibition of cyclooxygenase and 5-lipoxygenase distinguishes ginger from nonsteroidal anti-inflammatory drugs (NSAID’S), and partially accounts for its positive therapeutic profile, while having fewer side effects than nonsteroidal anti-inflammatory drugs [22,23]. Ginger has been shown to decrease pain in arthritis. Studies have demonstrated strong anti-inflammatory and anodynal properties that can use useful in Osteoarthritis, Rheumatoid arthritis and gouty arthritis [24-26]. Ginger has been shown to be excellent as a topical application for pain, [27] and can be ingested as well [28].

Cinnamon (Cinnamonium spp.)

Cinnamon is the source of a penetrating, medicinal oil derived from the bark {cortex} twigs or leaves of a tropical tree. In Chinese medicine, cinnamon is one of the most widely used warming herbs for promoting circulation in joints and limbs [29]. Cinnamon also aids in blood sugar regulation, which helps the body control overall inflammation. Topical application of cinnamon helps to improve circulation and ease discomfort. When applied topically, Cinnamon may redden the skin and produce a warming sensation.

When rubbed into painful, stiff joints, ligaments and muscles, traditional Chinese medicine believes that it “invigorates the blood and relieves stagnation, thus relieving pain. Cinnamon oil applied topically acts to release bradykinins. Continuous application results in depletion of bradykinins and reduction of muscle and joint aching and tenderness [30]. Cinnamon may also modulate inflammation by influencing NfKB receptors [31].

Wintergreen (Gaultheria procumbens)

Wintergreen is a low-growing evergreen shrub found in the damp woods of the Eastern United States. Methyl salicylate is one of the chief components that naturally occurs in wintergreen oil which is expressed from the plant. It has a distinctive pleasant aroma, and is often used as an extract for flavoring purposes. Methyl salicylate has chemical properties similar to salicylic acid - an aspirin like compound with the ability to allay
Pain [32]. Methyl salicylate is a common ingredient found in many over the counter salves and ointments. Many companies choose to use synthetic, petrochemically based methysalicylate, instead of natural Wintergreen Oil.

Peppermint (Mentha piperita)

Menthol is one of the principle essential oils derived from peppermint, and it has been historically used in Traditional Chinese Medicine (TCM). Menthol acts as a powerful analgesic when applied topically for various types of pain [33-34]. When menthol is applied to the skin, it initially produces a cooling sensation to inflamed areas, followed by a profound warmth.

Botanicals Taken Orally

White Willow Bark (Salix alba)

The use of willow bark dates back thousands of years, to the time of Hippocrates (400 BC) when patients were advised to chew on the bark of the White Willow tree to reduce fever and inflammation. White, Purple and Black Willow Bark (Salix alba, purpureaand Salix nigra), as well as members of the Poplar and Birch families, contain flavonoids, phenolic glycosides, including salicin, as well as salicin esters such as salicortin, fragalin and tremulacin . Some of these compounds are converted in the body into active salicylates, similar to the chemicals found in Aspirin. Thus, White Willow is often referred to as Nature's Aspirin. White Willow does not cause gastrointestinal bleeding as does Aspirin. This herb was traditionally used to support musculoskeletal health, ease the discomfort of aches and pains, reduce inflammation, fever and pain. Standardized extracts of Willow bark have been the subject of numerous research studies and clinical trials, which have proven its efficacy in pain amelioration [35-40]. The effectiveness of White Willow may be reduced if dysbiosis (imbalance in the gastrointestinal microflora) exists. This situation can be helped by taking probiotics such as acidophilus.

Bromelain

Bromelain is a proteolytic enzyme extracted from the stems and fruits of the pineapple plant. Beneficial therapeutic effects of bromelain have been shown in several human inflammatory diseases, including arthritis and inflammatory bowel disease. Bromelain helps break down fibrin, which causes swelling by accumulating in inflamed areas and blocking off blood and lymph fluid. Bromelain also inhibits platelet aggregation and adherence of antigens to cell surfaces, which supports its widely observed anti-allergic function. Anti-inflammatory effects may also be linked to bromelain’s ability to alter leukocyte migration and activation. Bromelain interferes with the production of prostaglandins and other substances that contribute to the inflammatory cascade, including eicosanoids, cyclooxygenases, and lipoxygenases [41,42]. Bromelain has been the subject of several successful clinical trials illustrating its efficacy in the treatment of osteoarthritis [43,44] Bromelain is often used successfully as a digestive aid. In this situation it should be taken with food at the end of a meal. For anti-inflammatory effects, bromelain should be taken on an empty stomach. For consistent therapeutic value, its best to use supplements containing specific amounts of bromelain. The therapeutic dose ranges from 500-2,000 mg, three times daily. Bromelain can cause sensitivity in people who are allergic to bee stings, olive tree pollen, pineapple, grass pollen, and other allergens. As a digestive aid, bromelain is usually used in combination with ox bile and hydrochloric acid.

Boswellia (Boswellia serrata)

This botanical is derived from the gum exuded from the Indian tree, Salai guggul (Boswellia serrata). The tree is scraped and the resin is allowed to exude from the tree until it dries. Boswellia is listed in Chinese Herbal Medicine under the pharmaceutical name ‘Gummi Olibanum’ or “Frankincense” [45]. Boswellia has been used for centuries by Ayurvedic physicians for arthritic conditions. In Traditional Chinese Medicine, Boswellia is used for static blood, invigorating and promoting the circulation of Blood and Qi, while relaxing the sinews. Modern research has documented boswellia’s ability to block inflammatory compounds which lead to a heightened pain response. Several constituents have been isolated, including the anti-inflammatory compounds 11-keto ßboswellic acid and Acetyl-11-keto ß-boswellic acid (AKBA), which inhibit leukotriene
biosynthesis through the impairment of 5-lipoxgenase(5-LO) [46]. Other active components in boswellia include mixed acetylboswellic acids and pentacyclic triterpenes. These compounds also have powerful anti-inflammatory and analgesic activity, and act by decreasing the production of pro-inflammatory molecules in articular cartilage [47]. Boswellia has been shown to prevent the interference with GAG (glycosaminoglycan)
synthesis, [48] and improves blood and lymphatic circulation to the joints. Based on a rat study, the non-phenolic ration of Boswellia serrata gum resin (20-300mg/kg) exhibits an analgesic effect similar to morphine (4.5mg/kg) [49] Clinical studies on humans have also revealed the potent anti-rheumatic activity of this phytomedicine. In one study, boswellic acids given to patients with osteoarthritis for six months caused a dramatic reduction in the levels of the inflammatory marker, C-reactive protein [50]. Boswellia shows efficacy in the treatment of both Rheumatoid and Osteoarthritis in humans [51-54]. Other studies support the use of boswellia in autoimmune conditions [55].

Jamaican Dogwood (Piscidia spp.)

Jamaican Dogwood was used historically as one of the most effective pain relievers by the Eclectic physicians at the turn of the 19th century. It was commonly recommended for fibromyositis, joint pain, dysmenorrheal and pain associated with bone fractures [56]. In the Amazon and Jamaican rainforests, the curanderos (healers) and 'Bush doctors' use the plant to treat migraines, joint pain, sprains, muscular aches and neuralgia [57,58].

Corydalis ( Corydalis ambigua) Yan Huo Su

In Traditional Chinese Medicine, Yan Hu Suo (Corydalis ambigua), a member of the Papaveracea family, has been used for thousands of years for its powerful analgesic properties. Many alkaloids have been isolated, with dl-tetrahydropalmatine (THP) and Corydalis L among the most potent. The analgesic potency of the rhizome is 1 to 10% that of Opium. The main alkaloids have been demonstrated to have a significant effect
that is equivalent to approximately 40% of the analgesic effects obtained by using morphine, without the addictive properties [59-61]. THP and related constituents share a naloxone-resistant analgesic action and have no affinity for opiate receptors, which accounts for their non-addictive nature. They have been found to be dopamine receptor antagonists [62]. Corydalis has been shown to strengthen the analgesic function produced by electro-acupuncture in mice [63] In a human trial, THP and its analogues, isolated from Corydalis , combined with Angelica, possessed analgesic activity and sedative-tranquilizing and hypnotic actions [64].

Ginger (Zingiber officinale)

Ginger is a widely used herbal medicine to aid with pain relief both via internal and external applications. Please visit the section on ginger above in “Topicals for Pain.

Turmeric (Curcuma longa)

Turmeric is a bright yellow spice used in preparing curry. It has powerful anti-inflammatory properties, which are credited to the chemical component curcumin.

Research suggests that turmeric suppresses nuclear factor kappa beta and interleukin-8, while enhancing glutathione biosynthesis [65]. Turmeric also inhibits NF-kappaB activation.

Chinese skullcap (Scutellaria baicalensis)Huang Qin

Chinese skullcap is often referred to as Scute, and is also known as Huang Qin in the traditional Chinese materia medica. It is one of the most widely used herbs in oriental medicine. It has a expansive range of therapeutic effects, including anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and amphoteric effects on the immune response. The active ingredients found in Chinese skullcap include natural anti-inflammatory flavonoids and flavans. The flavonoids baicalin, baicalein and wogonin, have potent anti-oxidant properties [66].

Scute displays anti-inflammatory effects by reducing the expression of nitric oxide (NO), inducible NOS (iNOS), Cyclooxygenase2 (COX-2), Prostaglandin E2 (PGE2), Nuclear Factor-kappaB (NF-kappaB) and IkappaBalpha as well as inflammatory cytokines, such as IL-1beta, IL-2, IL-6, IL-12 and TNF-alpha. This is achieved through the downregulation of IKKalphabeta, IkappaBalpha, NF-kappaB activation [67]. Other studies have illustrated this herb’s effect on the inhibition of the 5-LO pathway of arachidonic acid metabolism [68]. Research has illustrated Scute’s effectiveness in treating gout, or urate-crystal induced arthropathy, and inflammation in animal models. Scute diminished MSU crystal-induced inflammation by reducing neutrophil recruitment and expression of pro-inflammatory factors and increasing the level of the potentially anti-inflammatory prostaglandin D2 [69]. In a double blind human study, a proprietary mixture of baicalin from Scute and catechins, two anti-inflammatory flavonoids, was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. In this study, 103 subjects were randomly assigned to receive either the proprietary mixture of flavonoid molecules (baicalin and catechin, referred to as flavocoxid), [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. In this short-term pilot study, flavocoxid was found to be as effective as naproxen in controlling the signs and symptoms of OA of the knee and that it may present a safe and effective option for those individuals on conventional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors [70]. Scute has little known toxicity. The therapeutic dose is 2-6 grams per day.

References

  1. Radin EL, Paul IL (1972) A consolidated concept of Joint lubrication. J Bone Joint Surg Am 54(3): 607-613.
  2. Fernandes JC, Martel-Pelletier J, Pelletier JP (2002) The role of cytokines in osteoarthritis pathophysiology. Biorheology 39(1-2): 237-246.
  3. Bertschinger P, Zala GF, Fried M (1996) Effect of non-steroidal antirheumatic agents on the gastrointestinal tract: clinical aspects and pathophysiology. Schweiz Med Wochenschr 126(37): 1566-1568.
  4. Baggott JE, Morgan SL, Ha T, Vaughn WH, Hine RJ (1992) Inhibition of folate-dependent enzymes by non-steroidal anti- inflammatory drugs. Biochem J 282(Pt 1): 197-202.
  5. Balogh Z, El-Ghobarey AF, Fell GS, Brown DH, Dunlop J, et al. (1980) Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis. Ann Rheum Dis 39(4): 329-332.
  6. Lichtenstein DR, Wolfe MM (2000) COX-2-selective NSAIDs: New and improved? JAMA 284(10): 1297-1299.
  7. Ji H, Yao S, Luo Q, Cao X (2002) TCM Treatment of rheumatoid arthritis by supplementing the kidney and invigorating the blood circulation. J Tradit Chin Med 22(4): 252-255.
  8. Zhou X, Zhou Z, Jin M, Wang H, Wu M, et al. (2000) Intermediate and late rheumatoid arthritis treated by tonifying the kidney, resolving phlegm and removing blood stasis. J Tradit Chin Med 20(2): 87-92.
  9. Kang OH, Lee GH, Choi HJ, Park PS, Chae HS, et al. (2007) Ethyl acetate extract from Angelica Dahuricae Radix inhibits lipopolysaccharide-induced production of nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha via mitogen-activated protein kinases and nuclear factorkappaB in macrophages. Pharmacol Res 55(4): 263-270.
  10. Yuan CS1, Mehendale SR, Wang CZ, Aung HH, Jiang T, et al. (2004) Effects of Corydalis yanhusuo and Angelicae dahuricae on cold pressor-induced pain in humans: a controlled trial. J Clin Pharmacol 44(11): 1323-1327.
  11. Ratheesh M, Shyni GL, Sindhu G, Helen A, (2010) Protective effects of isolated polyphenolic and alkaloid fractions of Ruta graveolens L. on acute and chronic models of inflammation. Inflammation 33(1): 18-24.
  12. Ratheesh M, Shyni GL, Helen A (2009) Methanolic extract of Ruta graveolens L. inhibits inflammation and oxidative stress in adjuvant induced model of arthritis. Inflammopharmacology 17(2): 100-105.
  13. Takizawa Y, Isono T, Suzuki Y, Hayakawa Y, Oyama T (1992) Analgesic effects of Tsumura-shuuji-bushi-matsu and mesaconitine. Nihon Yakurigaku Zasshi 100(4): 307-316.
  14. Isono T, Oyama T, Asami A, Suzuki Y, Hayakawa Y, et al. (1994) The analgesic mechanism of processed Aconiti tuber: the involvement of descending inhibitory system. Am J Chin Med 22(1): 83-94.
  15. Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Toriumi M, et al. (2002) Anti-inflammatory and anti-tumor-promoting effects of cucurbitane glycosides from the roots of Bryonia dioica. J Nat Prod 65(2): 179-183.
  16. Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ (2004) Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 328(7446): 991.
  17. Szallasi A, Blumberg PM (1999) Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51 (2): 159-212.
  18.  Pini A, Baranowski R, Lynn B (1990) Long-term reduction in the number of C-fibre nociceptors following capsaicin treatment of a cutaneous nerve in adult rats. Eur J Neurosci 2(1): 89-97.
  19.  Jancso G, Lawson SN (1990) Transganglionic degeneration of capsaicin-sensitive C-fiber primary afferent terminals. Neuroscience 39(2): 501-511.
  20. Ali BH, Blunden G, Tanira MO, Nemmar A (2008) Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol 46(2): 409-420.
  21. Kamhi E, Zampieron E (1999) The Natural Medicine Chest. Natural Alternatives Health Education and Multimedia, Inc, New York, USA, pp.179.
  22. Grzanna R, Lindmark L, Frondoza CG 2005) Ginger--an herbal medicinal product with broad anti-inflammatory actions. J Med Food Summer 8(2): 125-132.
  23. Aggarwal BB, Shishodia S (2004) Suppression of the Nuclear Factor-kappaB Activation Pathway by Spice-Derived Phytochemicals: Reasoning for Seasoning. Ann NY Acad Sci 1030: 434-441.
  24. Srivastava KC, Mustafa T (1992) Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med Hypothesis 39(4): 342-348.
  25. Srivastava KC, Mustafa T (1989) Ginger (Zingiber officinale) and rheumatic disorders. Med Hypothesis 29(1): 25-28.
  26. Wigler I, Grotto I, Caspi D, Yaron M (2003) The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Osteoarthritis Cartilage 11(11): 783-789.
  27. Minghetti P, Sosa S, Cilurzo F, Casiraghi A, Alberti E, et al. (2007) Evaluation of the topical anti-inflammatory activity of ginger dry extracts from solutions and plasters. Planta Med 73(15): 1525-1530.
  28. Kamhi E, Zampieron E (1999) The Natural Medicine Chest. Natural Alternatives Health Education and Multimedia, Inc, New York, USA, pp. 179-181.
  29. Kamhi E, Zampieron E (1999) The Natural Medicine Chest. Natural Alternatives Health Education and Multimedia, Inc, New York, USA, p. 58.
  30. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, et al. (2004) Noxious Cold Ion Channel TRPA1 Is Activated by Pungent Compounds and Bradykinin. Neuron 41(6): 849-857.
  31.  Tsuji-Naito K (2008) Aldehydic components of cinnamon bark extract suppresses RANKL-induced osteoclastogenesis through NFATc1 downregulation. Bioorg Med Chem 16(20): 9176-9183.
  32. Higashi Y, Kiuchi T, Furuta K (2010) Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin Ther 32(1): 34-43.
  33. Davies SJ, Harding LM, Baranowski AP (2002) A novel treatment of postherpetic neuralgia using peppermint oil. Clin J Pain 18(3): 200-202.
  34. Taniguchi Y, Deguchi Y, Saita M, Noda K (1994) Antinociceptive effects of counterirritants. Nihon Yakurigaku Zasshi 104(6): 433-446.
  35. Chrubasik JE, Roufogalis BD, Chrubasik S (2007) Evidence of effectiveness of herbal anti-inflammatory drugs in the treatment of painful osteoarthritis and chronic low back pain. Phytother Res 21(7): 675-683.
  36. Chrubasik S, Eisenberg E, Balan E, Weinberger T, Luzzati R, et al. (2000) Treatment of low back pain exacerbations with willow bark extract: a randomized double blind study. Am J Med 109(1): 9-14.
  37. Ernst E, Chrubasik S (2000) Phyto-anti-inflammatories. A systematic review of randomized, placebo-controlled, double-blind trials. Rheum Dis Clin North Am 26(1): 13-27.
  38. Gagnier JJ, van Tulder MW, Berman B, Bombardier C (2006) Herbal medicine for low back pain. Cochrane Database Syst Rev 19(2): CD004504.
  39. Schmid B, Ludtke R, Selbmann HK, Tschirdewahn B, Schaffner W, et al. (2001) Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Phytother Res 15(4): 344-350.
  40. Setty AR, Sigal LH (2005) Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Semin Arthritis Rheum 34(6): 773-784.
  41. Hale LP, Greer PK, Trinh CT, James CL (2005) Proteinase activity and stability of natural bromelain preparations. Int Immunopharmacol 5(4): 783-793.
  42. Wallace JM (2002) Nutritional and botanical modulation of the inflammatory cascade--eicosanoids, cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy. Integr Cancer Ther 1(1): 7-37.
  43. Walker AF1, Bundy R, Hicks SM, Middleton RW (2002) Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine 9(8): 681-686.
  44. Brien S, Lewith G, Walker AF, Middleton R, Prescott P, et al. (2006) Bromelain as an adjunctive treatment for moderate-tosevere osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM 99(12): 841-850.
  45. Bone K (1996) Clinical Applications of Ayurvedic and Chinese Herbs. Monographs for the Western Herbal Practitioner. Phytotherapy Press, Australia, pp. 137-141.
  46.  Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, et al. (1992) Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther 261(3): 1143-1146.
  47. Blain EJ, Ali AY, Duance VC (2010) Boswellia frereana (frankincense) suppresses cytokine induced matrix metalloproteinase expression and production of pro-inflammatory molecules in articular cartilage. Phytother Res 24(6): 905-912.
  48. Reddy GK, Chandrakasan G, Dhar SC (1989) Studies on the metabolism of glycosaminoglycans under the influence of new herbal anti-inflammatory agents. Biochem Pharmacol 38(20): 3527-3534.
  49. Menon MK, Kar A (1971) Analgesic and psychopharmacological effects of the gum resin of Boswellia serrata. Planta Med 19(4): 333-341.
  50.  Chopra A, Lavin P, Patwardhan B, Chitre D (2004) A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an Ayurvedic drug, on osteoarthritis of the knees. J Clin Rheumatol 10(5): 236-245.
  51. Chopra A, Lavin P, Patwardhan B, Chitre D (2000) Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis. J Rheumatol 27(6): 1365-1372.
  52. Kimmatkar N, Thawani V, Hingorani L, Khiyani R (2003) Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee-a randomized double blind placebo controlled trial. Phytomedicine 10(1): 3-7.
  53. Kulkarni RR1, Patki PS, Jog VP, Gandage SG, Patwardhan B (1991) Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 33(1-2): 91-95.
  54. Kulkarni RR, Patki PS, Jog VP, Gandage, B Patwardban (1992) Efficacy of an Ayurvedic formulation in rheumatoid arthritis: a double-blind, placebo-controlled, cross-over study. Indian Journal of Pharmacology 24(2): 98-101.
  55. Ammon HP (2006) Boswellic acids in chronic inflammatory diseases. Planta Med 72(12): 1100-1116.
  56. Felter, HW (1922) Eclectic Materia Medica Pharmacology and Therapeutics. In: Sandy Oregon (Eds.), Eclectic Publications, revised 1998, pp. 385-390.
  57. Kamhi E, Zampieron E (1999) The Natural Medicine Chest. Natural Alternatives Health Education and Multimedia, Inc, Oyster Bay, New York, USA, pp. 188-190.
  58. Della Loggia R, Zilli C, Del Negro P, Redaelli C, Tubaro A (1988) Isoflavones as spasmolytic principles of Piscidia erythrina. Prog Clin Biol Res 280: 365-368.
  59. Bensky D, Gamble (1986) A: Chinese Herbal Medicine Materia Medica, Eastland Press, Seattle, USA, p. 62.
  60. Tang W, Ejsenbrand (1992) G: Chinese Drugs of Plant Origin, Springer Vetlag, Berlin.
  61. Chang HM (1987) Pharmacology and Applications of Chinese Materia Medica. (Volume 1), World Scientific, Singapore.
  62. Zhu XZ (1991) Development of natural products as drugs acting on central nervous system. Mem Inst Oswaldo Cruz Suppl 2:173-175.
  63. Jin GZ (1978) Acta Physiol Sinica 30,67 Hu, J et al Chen Tzu Yen Chiu Acupuncture Research 19,55 (1994).
  64. Yuan CS1, Mehendale SR, Wang CZ, Aung HH, Jiang T, et al. (2004) Effects of Corydalis yanhusuo and Angelicae dahuricae on cold pressor-induced pain in humans: a controlled trial. J Clin Pharmacol 44(11): 1323-1327.
  65. Biswas SK, McClure D, Jimenez LA, Megson IL, Rahman I (2005) Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity. Antioxid Redox Signal 7(1-2): 32-41.
  66. Chan E, Wong CY, Wan CW, Kwok CY, Wu JH, et al. (2010) Evaluation of Anti-Oxidant Capacity of Root of Scutellaria baicalensis Georgi, in Comparison with Roots of Polygonum multiflorum Thunb and Panax ginseng CA Meyer. Am J Chin Med 38(4): 815-827.
  67. Kim EH, Shim B, Kang S, Jeong G, Lee JS, et al. (2009) Anti-inflammatory effects of Scutellaria baicalensis extract via suppression of immune modulators and MAP kinase signaling molecules. J Ethnopharmacol 126(2): 320-331.
  68. Butenko IG, Gladtchenko SV, Galushko SV (1993) Anti-inflammatory properties and inhibition of leukotriene C4 biosynthesis in vitro by flavonoid baicalein from Scutellaria baicalensis georgy roots. Agents Actions 39 Spec No: C49-C51.
  69. Jung SM1, Schumacher HR, Kim H, Kim M, Lee SH, et al. (2007) Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels. Arthritis Res Ther 9(4): R64.
  70. Levy RM1, Saikovsky R, Shmidt E, Khokhlov A, Burnett BP (2009) Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized, doubleblind pilot study. Nutr Res 29(5): 298-304.
© 2014-2016 MedCrave Group, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use.
Creative Commons License Open Access by MedCrave Group is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://medcraveonline.com
Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version | Opera |Privacy Policy