Roles Of NR2B In The Spinal Dorsal Horn Of Rats With Diabetic Neuropathic Pain

Objective: As we konw, the neuropathies are one of the most common long-time complications of diabetes, and the morbility increses every year. The pathological changes of sensory nerve is most common in the neuropathies which take part in about 30%. The mechanisms of diabetic neuropathic pain are very complex and the management is still quite difficult. Studies on the transmitter phmaraeology have indicated that there existed changes of neurotransmitters and receptors in spinal cord induced by neuropathic pain. Changes of NR2B could affect the transmission and modulation of nociceptive messages.The persent study is to explore changes of NR2B in spinal cord dorsal horn of rats with diabetic neuropathic pain induced by STZ. Characteristic behavioral changes were observed to affect hyperalgesia and fasting blood-glucose between the groups of DM and Control,and we also observe the change of 50% paw withdraw threshold(PWT) of rats with diabetic neuropathic pain. Methods of immunohistochemistry was applied to examine the expression of NR2B in spinal cord dorsal horn. Studies about the changes of NR2B in spinal cord dorsal horn could help finding out more specific targets of treatment for diabetic neuropathic pain.Methods: 60 male Sprague-Dawley rats were randomly selected for this experiment, weighing 130g-150g. Body weights, fasting blood glucose level and 50% paw withdraw threshold of all the rats were measured before STZ injection. 48 rats were induced with a single intraperitoneal injection of streptozocin(60mg/kg) as diabetes. At one week after STZ injection, 30 rats whose fasting blood glucose level increased up to 16.7mmol/L were consided as diabetic rats, and the ratio is 63%. At two week after STZ injection, responses to the mechanical stimulus of diabetic rats were measured with von Frey filament, and whose 50% paw withdraw threshold(PWT) were down to 4g were consided as diabetic neuropathic pain models. Another 12 rats were were intraperitoneal injected of saline as controls.20 diabetic rats and 12 normal rats were randomly selected for behavioral and biology experiment. 20 diabetic rats were separated into 4 groups by different time points at 2, 3, 5, 7 week after STZ injection. Body weights, fasting blood glucose level and PWT were measured in diabetic and control rats in every time point. At 2, 3, 5, 7 week after STZ injection, diabetic rats which PWT were down to 4g were sacrificed and intumescence segments of spinal cord were collected for analysis of NR2B in the spinal cord dorsal horn for Immunohistochemistry. 12 control rats were sacrificed for analysis of NR2B at 2,3,5,7 week after normal saline injection.Data analysis and statisties. Data were expressed as mean±SEM. The results were analyzed by? rank-sum test of variance(ANOVA). Values of P<0.05 were considered as statistically significant.Results:1 Before STZ injection, the level of body weights, fasting blood glucose and 50% paw withdraw threshold had no Statistical difference between diabetic and control groups. To compare with control group, the level of fasting blood glucose in diabetic group increased dramatically at 2,3, 5, 7 week after STZ injection (p<0.05), while it aslo had significant Statistical difference compared with it was before STZ injection (p<0.05). Body weights and 50% paw withdraw threshold decreased significantly after STZ injection in diabetic group (p<0.05), and aslo they had significant Statistical difference compared with they were before STZ injection (p<0.05).2 To compare with control group, immunoreactivity for NR2B in the spinal cord dorsal horn of rats with diabetic neuropathic pain significantly increased at 2,3, 5, 7 week after STZ injection (p<0.05),and the most amount at 3 week, and it began to decrease at 5 week.Conclusion: NR2B in the spinal cord dorsal horn are involved in the regulation of diabetic neuropathic pain.