Role of Spinal Cord Microglia in the Pathogenesis of Diabetic Neuropathic Pain in Rats

Objective To investigate the activation of spinal cord microglia,the content change of substance P and the effect of minocycline in rats with diabetic neuropathic pain.Methods Thirty-six Wistar male rats were prepared for diabetic neuropathic pain model by STZ intraperitoneal injection,another 12 rats were selected as control group(group C).The model rats were respectively given minocycline at a dose of 40 mg/kg(group M4),20 mg/kg(group M2),0 mg/kg(equal volume of PBS,group D) for 29 d before STZ injection.The paw withdrawal mechanical threshold(MWT) were determined at the following time points:the day before STZ injection,and the 7 d,14 d,21 d,28 d after injection(t1～5).The rats were sacrificed and the spinal cord were taken at t5.The content of substance P in spinal cord was deteced by immuno-histochemical assay,the expression of microglia marker protein CR3 was detected by RT-PCR.Results Compared with group C,the value of MWT and content of substance P were decreased,but the expression of CR3 mRNA was increased in group D(P0.05).Compared with group D,the value of MWT was increased in group M4,the content of substance P was increased and expression of CR3 mRNA were decreased in both group M4 and group M2(P0.05).Compared with group M2,the value of MWT and content of substance P were both increased in group M4(P0.05),but the expression of CR3 mRNA had no significant difference between these two groups(P0.05).Conclusion The pathogenesis of diabetic neuropathic pain may correlate with the activation of spinal cord microglia,the content of substance P was decreased in rats model.Minocycline could inhibit the activation of spinal cord microglia,meanwhile the content of substance P was increased and the neuropathic pain was improved.