Inflammatory Pain
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Inflammatory Pain

Inflammation is a protective nonspecific response to such things as injury, infection, chemicals & toxins, foreign bodies, autoimmune responses etc. Inflammation may produce pain, swelling, redness, blisters, pus, ulcers, necrotic or fibrous tissue. It proceeds in a sequential and orderly fashion until resolution of the problem. Except when it does not- resulting in permanent tissue dysfunction from scarring, or chronic inflammation. Sequence:

  1. vasodilatation (redness & heat)
  2. vascular permeability & leakage of fluid into tissue (swelling & pain)
  3. recruitment and infiltration of neutrophils into damaged tissue.
  4. neutrophils digest damaged tissue and pathogens
  5. formation of new healthy tissue, scar tissue or chronic inflammation

Inflammation also involves not so orderly pro inflammatory mediators: histamines, clotting factor & platelets, bradykinins (pain), free radicals (ROS), nitric oxide (vasodilatation), cyclo oxygenase (COX), thromboxane. prostaglandin, leukotrienes, substance P, neurokinins. Cells: monocytes/ macrophages & granuloma  etc. Tissues: connective, blood vessels, and collagen. Cytokines: growth factors (GF), interleukins (IL), tumor necrosis factors (TNF); and interferons (viral immunity) are among complex inflammatory mediators that are engaged in the immune response when inflammation is due to virus, bacteria, endotoxins, stress, tumors etc. 

INFLAMMATORY PATHWAYS
The Arachidonic pathway = prostaglandin (vasodilatation, pain, fever, clotting), leukotrienes (vasoconstriction, vasopermeability, and thromboxane (clotting/ platelet adhesion, and vasoconstriction). It is the cornerstone under which other pathways fall. Steroids block the Arachidonic pathway. 

The COX I pathway = Thromboxane and Protacyclin (protects the stomach lining fro its own acidity). It is moderated with non steroidal anti-inflammatory drugs (NSAIDs like Ibuprofen). Chinese herbs that act on this pathway are dang gui, qiang huo, xuan shen, ren shen, gan cao, ci wu jia. These herbs do not inhibit Protacyclin, Therefore they do not cause gastric erosion and bleeding like non-selective NSAIDS and aspirin do.

The COX II pathway = Prostaglandins, which cause vasodilatation. It is moderated with aspirin and Ibuprofen. Chinese herbs that act on this pathway are fang ji, zhi mu, dang gui, qiang huo, ren shen, gan cao, and ci wu ji.

The 5-Lipoxygenase (5-LOX) pathway = Leukotrienes which are engaged with seasonal allergies/ hay fever. It is treated with Leukotriene inhibitors. 5-Chinese herbs that affect this pathway are qiang huo, and xuan shen. Also herbal formulas like Jade Wind Screen that stabilize the exterior prior to allergy season.

IMMUNE RESPONSES
The inflammatory response to virus, bacteria, endotoxins, stress, tumors etc. involves humeral & cellular activity (macrophages, leukocytes, lymphocytes etc). It is sometimes moderated with steroidal drugs. Gan Cao/ licorice and Xuan Shen are notable Chinese herbs that have steroidal-like action:

  • Gan Cao works at the level of the adrenals and mineralcorticoids.
  • Xuan Shen affects most pathways under the Arachadonic pathway, as well as the inflammatory immune response. Cited by the article below, it is twice as potent as indomethacin (NSAID) for inflammatory pain.

Histamines are released by mast cells when a person is exposed to an allergen, and then experiences a type I /IgE-mediated immune response Histamine is an inflammatory mediators that is moderated with mast cell stabilizers, antihistamines (Benadryl), and sometimes with epinephrine  for anaphylactic reactions. Among the Chinese herbs shown to stabilize mast cells are garlic bulb, ginkgo leaf, er bu, centipeda, dang gui/rehmannia root, dang shen/salvia root, turmeric root. Scute root/ huang qin, coptis rhizome/ huang lian, phellodendron bark/huang bai, and gardenia fruit/ zhi zi were shown to suppress anaphylactic histamine release in an animal model.

Other herbs that moderate immune responses are:
  • Mo Yao/ myrrh and Ru Xiang/ frankincense, both from regulate and invigorate blood category. It inhibits macrophages, chemokines and TNF.  The boswellic acids in ru xiang may also inhibit LOX and COX1 pathways, with fewer side effects than steroids and NSAIDS. But it fails to show the same analgesic effect.  It may potentiate the effect of certain anticoagulant medications.
  • Sang Ji Sheng/ mulberry stems from release wind-damp category
  • Aconite/ chuan wu & cao Wu
  • Qiang Huo
  • Dang Gui

CHINESE HERBS AND INFLAMMATION
The beauty of Chinese herbs is that they treat inflammatory pain with out side effects/adverse reactions.  The stage and cause of the inflammation according to Chinese medical theory (the differential diagnosis) determines which herb(s) are used and when. English (2013), cites the Chinese herbs, from diverse categories, that are shown to inhibit inflammatory pathways and mediators as described above:
 
Gastrodia/ Tian Ma from extinguish wind & stop tremor category, Affects nitric oxide (NO) production and 5-LOX pathway. Inhibits inflammatory clot formation with no affect on normal clotting.
 
Aconite/ Cao Wu & Chuan Wu from warm the interior & expel cold category. Reduces sodium channel involved in nerve transmission and hyperactive nociceptive pain responses. Modulates the beginning stages of inflammation.
 
Scrophularia/ Xuan Shen from clear heat & cool blood category. Inhibits infiltration/proliferation of T cells, 5-LOX pathway, inflammatory PGEs, ILs, TNFs, and NO production. No affect on anti-inflammatory cytokines.
 
Notopterygium/ Qiang Huo from warm acrid & release exterior category. Inhibit 5-LOX and COX pathways.
 
Eucommia/ Du Zhong from tonify yang category. Inhibitor of mast cells.
 
Ligusticum/ Chuan Xiong from regulate & invigorate blood category. Inhibits TNFs and mast cell activation.
 
Rehmannia/ Shu Di Huang from tonify blood category. Inhibits TNFs and ILs. Reduces the production of pro-inflammatory factors at the nerve/ neuron level.
 
Achyranthes/ Nui Xi/ Huai Nui Xi from regulate & invigorate blood category. Strongly inhibits the infiltration/proliferation of neutrophils to the site of tissue injury. These neutrophils otherwise attack and damage normal tissue.
 
Dang Gui / Dang Shen from tonify blood category. Inhibits TNFs, ILs, inflammatory PGEs, mast cells; and the recruitment/infiltration of neutrophils. Enhances anti-inflammatory PGEs. Protects cells from free radical damage occurring in chronic inflammation.  It plays an important role in the treatment of osteoarthritis. While it ameliorates acetomiophen-induced liver damage. It may potentiate the effect of anticoagulant medications (Warfarin, heparin, enoxaparin); or antiplatelet drugs (aspirin, dipyridamole and clopidogrel. 



Sources
Chen, J. (n.d.) Anti-Inflammatory effects of herbs: TCM research and applications. Lotus Institute of Integrative Medicine.

English J. (2013).Traditional Chinese herbs for arthritis [Digital version]. Nutrition Review. Retrieved from http://nutritionreview.org/2013/04/traditional-chinese-herbs-arthritis/. 

Minarcik, J. (2008). Medical School Pathology, Chapter 2a: Inflammation [Video file]. Retrieved from www.youtube.com/watch?v=-iwRlFFFFQ8&list=PLDAE44B29B0964058&index=6. 

Page, R.,  Lawrence, J., (1999). Potentiation of warfarin by dong quai. Pharmacotherapy 19(7), 870-6. Retrieved from www.ncbi.nlm.nih.gov/pubmed/10417036

Paoletti, A., et al. (2011). Interactions between natural health products and oral anticoagulants: Spontaneous reports in the Italian Surveillance System of Natural Health Products. Evidence-Based Complementary and Alternative Medicine . doi:10.1155/2011/612150.  Retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC3025393/

Singh, G., Atal, C. (1986). Pharmacology of an extract of salai gugal ex-Bowellia serrata, a non-steroidal antiinflammatory agent. Agents Actions 18(3-4), 407-412.



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