| Postgraduate for pH. D ChenHua Tutor Cui jianjunFollowing brain research become key point in the last ten years of twenty century, pain research has become important in the first ten years of twenty one century which suggest that pain is very important and urgent issue in daily life. Neuropathic pain arising from peripheral or central nerve injury is a clinical disorder characterized by spontaneous pain, hyperalgesia and allodynia. The mechanism is complex, and the treatment is difficult. Since there is not a kind of drug that has long analgesics, less side effect. So combination of analgesics from different pharmacological classes is still the main way to control neuropathic pain.In recent years a series of clinical studies have reported that opioids are the most widely used and most effective drugs for the treatment of non-cancer patients. However, there is no real consensus in terms of opioids in the management of neuropathic pain. Since opioids were reported to be not effective in one study, whereas in another, was shown to produce good analgesia. Thus, it appears that the efficacy of morphine in attenuating hyperalgesia in these studies is largely depend on the animal model, the measurement, the route of drug administration , the type of nerve injury and partly the time of treatment to the neuropathy. On the other hand, there is abundant evidence for a major role for the N-methyl-D-aspartate (NMDA) receptor in the generation of central sensitization, the principal factor for the development and maintenance of neuropathic pain. It has been shown that NMDA receptor antagonists reduce the nociceptive response and hyperalgesia in experimental models of chronic pain as well as wind - upphenomena and tolerance to morphine. But drugs used in these studies are mainly those that not to be applied in clinical such as Mk-801, furture more, the mechanism was still on spinal level. One clinic research showed that chronic intrathecal ketamine enhances the analgesic effect of morphine and reduces the dose of intrathecal morhine in patients with terminal cancer pain, but how the effect of their combination intrathecally to control neuropathic pain has not been reported. Thus, in present study, we investigate the effect of chronic intrathecal coadministration morphine and ketamine on thermal hyperalgesia in rats with sciatic constriction injury, expore its mechanism on spinal and supraspinal levels. This study is divided into three section; First, Effect of intrathecal chronic coadministration morphine and ketamine on thermal hyperalgesia in rats. Second, the antinociceptive mechanism of intrathecal morphine and ketamine on spinal level. From the effect to ultra - structure of sensory neurons in dorsal root ganglion (DRG) , to the product of Nitric oxide ( NO) , activity of Nitric oxide syn-thase (NOS) and Acetylcholinesterase ( AchE) in spinal cord, to substance P in the superficial dorsal horn, and to the mRNA expression of jx-opioid receptor and NMDA receptorl in spinal cord. Third, The antinociceptive mechanism of intrathecal morhine and ketamine on supraspinal level. From the effect to the product of NO , activity of NOS and AchE, to the mRNA expression of jx-opioid receptor and NMDA receptor in cerebral cortex ^ hippocampus and brainstem.Materials1. Animals; healthy male wistar rats weighing 200 -250g were used in this study.2. Kits and drugs;Kits of NO, NOS, AchE; Kit of SP immunohistochemis-try; Primers of -opioid receptor and NMDA receptor, p-action; PCR marker, Takara kit; morphine hydrochloride, ketamine hydrochloride.3. Equipment; H-600 transmission electron microscope; KODAKID gel imaging analytical system; RTC - 100 PCR amplification device; HERMLEZ 383 K high speed centrifuger; BX60 olympus microscopic camera; METAMORPH/ COOL SNAP + X/AX70 microscope photograph analytical system; LKB - V typeultrathin slicer.Methods1. Animal modelMononeuropathy was produced according to the method described by Bennett and Xie. A catheter was inserted in...
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