Effects Of Dezocine On NMDA-2B Receptor Subunits Expression In The Spinal Dorsal Horn Of Rats With Diabetic Neuropathic Pain

Objective: The diabetic peripheral neuropathic pain is one of theneuropathic pain, and the diabetic peripheral neuropathy is one of the mostcommon long-time complications of diabetes. About7.5%-24%of diabeticpatients suffer chronic peripheral neuropathic pain. The mechanisms ofdiabetic neuropathic pain are very complex. Central sensitization play animportant part in diabetic peripheral neuropathy, and NMDA receptors areimportant components of system of spine excitatory glutamic acid receptorswhich participate in the central sensitization.The synthetic drug of dezocine is a new opioid agonists and antagonistdrug. Because of its low adverse effect, it has been used in clinical in wideapplication. It has been demonstrated that opioid agonists are effectivetreatment for the diabetic peripheral neuropathic pain. The persent study is toevaluate the effects and the mechanism of dezocine on NMDA-2B receptorsubunits through the rats with diabetic neuropathic pain induced by STZ. TheWeight, the fasting blood glucose and the50%paw withdraw threshold will beobserved on Normal group, Dezocine group and Control group. Methods ofimmunohistochemistry and RT-PCR were applied to examine the expressionof NMDA-2B receptors in spinal cord dorsal horn. The study could helpfinding out more specific target of treatment for the diabetic peripheralneuropathic pain.Methods: Eighty male Sprague-Dawley rats were randomly selected forthis experiment, weighing130-150g. Body weights, fasting blood glucoselevel and50%paw withdraw threshold of all the rats were measured beforeSTZ injection. Sixty rats were induced with a single intraperitoneal injectionof streptozocin(60mg/kg) as diabetes. At one week after STZ injection,45ratswhose fasting blood glucose level increased up to16.7mmol/L were consided as diabetic rats, and the ratio is75%. At two week after STZ injection,responses to the mechanical stimulus of diabetic rats were measured with VonFrey filament, and whose50%paw withdraw threshold(PWT) were down to4g were considered as diabetic neuropathic pain models. The rest of rats are asControl group.Thirty six diabetic rats were randomly assigned to two groups, eighteenin each group: group one as Control group; group two as Dezocine group.Eighteen normal rats were randomly chosed as Normal group. At two weeksafter STZ injection, rats of dezocine group were induced with a singleintramuscular injection of dezocine (2.25mg/kg), which continued one weekand rats of Control group and Normal group were induced with a singleintramuscular injection of saline(the same volume as Dezocine group), whichcontinued one week. Rats of three groups were separated into3groups bydifferent time points at3,5,7week after STZ injection. Body weights, fastingblood glucose level and PWT were measured in three groups at every timepoint. Intumescence segments of spinal cord were collected for analysis ofNMDA-2B receptors in the spinal cord dorsal horn for Immunohistochemistryand RT-PCR.Data analysis and statisties. Data were expressed as mean±SEM. Theresults were analyzed by T-test and analysis of variance(ANOVA). Values ofP<0.05were considered as statistically significant.Results: Studied from the general situation and the molecular biologyaspects.1Before STZ injection, the level of body weights, fasting blood glucoseand50%paw withdraw threshold(PWT) had no Statistical difference in threegroups(p>0.05). The50%paw withdraw threshold(PWT) had Statisticaldifference between Control group and Dezocine group at3week(p<0.05),hadn't Statistical at5week,7week(p>0.05). The level of body weights,fasting blood glucose had no Statistical difference between Control group andDezocine group after dezocine injection(p>0.05).2To compared with Control group, immunoreactivity for NMDA-2B receptors in the spinal cord dorsal horn of rats with Dezocine groupsignificantly decreased at3week after STZ injection. It had statisticaldifference between Control group and Dezocine group (p<0.05). The mRNAlevel of NMDA-2B receptors Statistical decreased at3week after STZinjection, it had statistical difference between Control group and Dezocinegroup (p<0.05).Conclusion: Dezocine had an effort on the diabetic peripheralneuropathic pain; The possible mechanism of dezocine inhibition the diabeticperipheral neuropathic pain is reducing the expression of NMDA-2B in thespinal cord dorsal horn.