Neurobiological Mechanism Of Electro-Acupuncture Combined With Tramadol In Chronic Inflammatory Pain

Neurobiological Mechanism of Electro-Acupuncture combined with Tramadol in Chronic Inflammatory Pain Chronic pain is common disease in clinics. Substantial evidences have indicated that electro-acupuncture (EA) is an effective method for analgesia and has been used in clinics. EA plays its analgesic role via activating the endogenous pain modulating systems, including endogenetic opioid and serotonin descending system. In order to improve EA analgesic effect and wide use of EA in clinics, large amount of previous studies in our lab suggested that the combination of EA with small dose of analgesics could enhance analgesic effect of EA. EA combined with some drugs could either improve analgesia or decrease drug dose, suggesting that it might be more perfect treatment.Tramadol is a clinically-effective opioid analgesic. It could reduce post-operative wound pain, neuropathic pain, inflammatory pain and so on. The efficacy and potency of tramadol is only five to ten times lower than that of morphine, although its affinity to (-opioid receptor is 6000 times less than morphine, suggesting that tramadol reduces nociception by other mechanism. It includes that tramadol enhances the extracellular concentration of the monoamine neurotransmitters serotonin (5-HT) and noradrenaline (NE) by interference with the uptake and release. It is demonstrated that the analgesic effect of either tramadol or EA is related with endogenetic opioid and serotonin system. However, it thas not yet been studied whether tramadol could potentiate EA analgesia, by using together.It has been known that 5-HT system plays an important role in pain modulation system and 5-HT 2A receptor mRNA was expressed in some brain nucleui involved in pain modulation and spinal dorsal horn. The previous studies of our lab revealed that the expression of 5-HT2A receptor mRNA was increased following carrageenan injection, suggesting that 5-HT 2A receptor in brain stem and spinal dorsal horn may contribute to suppress the acute inflammatory pain. It is unclear how the expression of 5-HT2A receptor mRNA changes during complete Freund's adjuvant (CFA)-induced chronic inflammatory pain. Moreover, some reports showed that EA enhanced 5-HT synthsis and release, on the other hand, tramadol inhibited 5-HTuptake. How is level of 5-HT in the central nervous system influenced by chronically using tramadol and EA?Orphanin FQ (OFQ), a newly discovered heptadecapeptide, is involved in pain modulation. The studies of our lab indicated that OFQ participated in acute inflammatory pain and neuropathic pain. How does endogenous OFQ change during chronic inflammatory pain? Furthermore, Some studies showed that OFQ system was related with 5-HT release, suggesting that it is relative between OFQ and 5-HT system. Now that the level of 5-HT in synaptic space increases because of inhibitory effect on 5-HT re-uptake of tramadol, whether will OFQ synthesis be influenced after chronically using tramadol and/or EA?Some reports showed that inflammatory pain was mediated and maintained by adenylyl cyclase activity and protein kinase A (PKA). It is not clear that whether intercellular mechanisms of tramadol and EA analgesia is involved in cAMP-PKA signaling transductive pathway.On monoarthritic rat model that injection of CFA into the tibio-tarsal joint of the rat produced a monoarthritic model, by using the paw withdrawal reflection to radiant heat experiment, the present study was designed to investigate the changes of thermal hyperalgesia, to confirm the analgesic effects of tramadol and EA on arthritic rats, including immediate effects of single treatment and accumulative effects of chronic treatment. Furthermore, by using the molecule biological techniques, including in situ hybridization, immuneohistochemistry, double labeled of fluorescein, RT-PCR and Western-Blot, the influences on 5-HT and OFQ system in CNS and the signal transductional pathway of EA combined with tramadol are investigated, in order to give an insight understanding of the p...