Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by recurrent abdominal pain and disturbance in bowel movements. The exact mechanism of IBS is poorly understood but mounting evidence suggests that visceral hyperalgesia and psychosocial stress play important roles in the pathogenesis. Serotonin (5-HT) is abundant in gastrointestinal tract and one of the major neuropeptides involved in pathogenesis of IBS. In rodent models, persistent visceral hyperalgesia in the adulthood can be induced by stressors during neonatal period such as neonatal maternal separation and rectal balloon distension. We have previously reported that early life stressors can lead to enhanced responsiveness of serotoninergic pathway in enteric nervous system. Theoretically, visceral hyperalgesia and irritable bowel syndrome may be treated by reversal or inhibition of enhanced activity of serotoninergic pathway. Unfortunately, medical treatment of IBS has been disappointing. Although a few 5-HT receptor modulators are marketed for treatment of IBS in recent years, there has been concern about the safety of these drugs. On the other hand, acupuncture has been used extensively for treatment of various painful conditions and gastrointestinal diseases in Traditional Chinese Medicine. According to Chinese medical theories, the most common cause of IBS is the """"""""stagnation of liver energy attacking the spleen and resulting in dysfunction of the transportation and transformation function of the spleen"""""""". This is a condition characterized by a syndrome of recurrent abdominal pain, diarrhea and psychological conditions such as depression and anxiety. Based on the principle of TCM, as mentioned in the Yellow Emperor's Inner Classics, the most ancient TCM medical book, one should """"""""use herbs to treat the illness internally and acupuncture to treat externally"""""""". Our previous studies have revealed that electroacupuncture (EA) produces prolonged anti-inflammatory and anti-hyperalgesic effects in rats with complete Freund's adjuvant (CFA)-induced inflammatory hyperalgesia. It has been reported that EA-induced anti-inflammation and anti-hyperalgesia involves modulation of functions in the neuroendocrine system including serotoninergic system. Thus, acupuncture may be a promising treatment for IBS. The objective of this study is to evaluate the visceral anti-hyperalgesic effect of EA and its mechanism in a rat model of visceral hyperalgesia. We hypothesize that EA modulates the central processing and peripheral signaling functions in visceral nociceptive pathways, and thereby alleviates visceral hyperalgesia.
The specific aims of the study are: 1. To determine the effect of EA on behavioral and visceromotor response to visceral pain in rat model of visceral hyperalgesia. 2. To determine the effect of EA on colonic mucosal serotoninergic signaling in rats with visceral hyperalgesia. 3. To determine the effect of EA on serotoninergic activites at spinal cord level in rats with visceral hyperalgesia. 4. To determine the effect of EA on serotoninergic activites in dorsal raphe nucleus and raphe nucleus magnus, the relay centers of central descending inhibitory pathway, in rats with visceral hyperalgesia.
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