Establishment And Application Of Evidence-based Experimental Medicinal Methods On Screening Anti-nociceptive And Anti-inflammatory Traditional Chinese Medical Herbs

The Traditional Chinese Medical (TCM) herbs have been long used as analgesic and anti-inflammatory drugs in clinic. However, due to severe lack of Good-Clinical-Practice (GCP) trials that should be in accord with randomly-divided, double-blind and placebo-controlled standard (RDP standard), the efficacy of the TCM analgesics and anti-inflammatory drugs has not been world-widely accepted. On the other hand, the knowledge about pain and its underlying mechanisms has been greatly changed due to the findings that-10-functional and/or structural plasticity or change can be induced in the central somatosensory system following peripheral tissue and nerve injury (pathological pain state). Therefore pain can be generally divided into physiological and pathological types. The former is transient in duration and plays an alarm function to tell where, what and how pain is produced (good and wanted pain). Under physiological state, there is no spontaneous pain and hyperalgesia (allodynia), nor is there inflammation and obvious tissue or nerve injury. The animal models which can be used to test normal nocifensive threshold are tail flick test and hot plate test. While the latter is persistent or chronic in duration and often occurs spontaneously and shows abnormally sensitive (hypersensitivity and hyperalgesia or allodynia) to natural stimuli such as thermal and mechanical stimuli and is not wanted by human life (bad and unwanted pain). Under pathological state, tissue or nerve injury is often the origin of pain and some types of pain are insensitive to conventional pain-killers (analgesics). The animal models which can mimic pathological pain are of particular importance and useful in study of pathological pain mechanisms and in screening novel effective endogenous or exogenous analgesics.The present study is trying to establish a new method for screening TCM herbs based on experimental evidence-based knowledge by using two persistent pathological pain models: the bee venom test and the formalin test.Subcutaneous (s.c.) injection of bee venom (BV) solution into one hindpaw of rats has been demonstrated to be able to produce a prolonged time course of persistent spontaneous pain-related behaviors such as flinching reflex in a monophasic manner for 1 h, and accompanied by a subsequent period of profound, persistent primary thermal and mechanical hypersensitivity (hyperalgesia) in the-11- injected hind paw for 3-4 days. Meanwhile, s.c. BV injection also produces a striking edema and redness of the plantar surface for nearly the same period as the development of hyperalgesia. Injection s.c. of formalin solution can produce two phases of persistent pain-related behavior but without obvious hyperalgesia and allodynia. Both of the two animal models are suitable to study the effects of TCM herbs on tissue-injury induced pain and/or hyperalgesia and inflammation.According to the natures of TCM, Chinese herbs have been divided into three classes: Mild class, Warm-Heat class and Cool - Cold class. In the present study, effects of the three classes of TCM herbs were tested to see whether they could produce the same effects on persistent spontaneous pain, heat and mechanical hyperalgesia (or allodynia) and inflammatory responses (such as edema and plasma extravasation).Moreover, to see whether the three classes of TCM drugs are effective in both prevention and relief of the peripheral chemical tissue-injury induced pain, hyperalgesia and inflammation, the drugs were administered: (1) 10-30 min prior to chemical pain-producing agents; (2) 5-10 min after good establishment of persistent pain; (3) 2-4 h after good establishment of the thermal and mechanical hyperalgesia as well as inflammation. The major results are as follows:Anti-nociceptive effects of TCM herbs1. Effects of TCM herbs on the chemical tissue injury-induced persistent spontaneous pain-related responses-12-(1) Effects o/the Mild class of TCM herbsTo study anti-nociceptive effects of the Mild class of TCM herbs...