The role of NMDA receptors in the effects of corticosterone on CCI model neuropathic pain in rats

Previous studies have shown that glucocorticoids play an important role in neuropathic pain behaviors, but the underlying mechanisms are not known. The aim of this study was to determine the role of NMDA receptors in the effects of glucocorticoids on neuropathic pain behaviors in CCI model in rats. Male adult Wistar rats (200-300 gram) were used in this srudy. Chronic constriction nerve injury (CCI) rats were produced by loosely ligating a common sciatic nerve. Two weeks after inducing CCI, the effects of corticosterone in the presence or absence of MK-801 (a bloker of NMDA receptor) were studied. Behavioral pain responses (thermal hyperalgesia and thermal and mechanical allodynia) were studied using standard procedures. Findings indicated that peripheral administration of corticosterone suppressed both hyperalgeisa and allodynia in a dose-dependent manner. MK-801 (0.3 mg/kg) pretreatment attenuated the effects of corticosterone (15mg/kg) on both thermal hyperalgesia and mechanical allodynia. Also MK-801 alone suppressed thermal allodynia, but not thermal hyperalgesia and mechanical allodynia. These findings show that glucocorticoids play an important role in neuropathic pain behaviors. It seems that at least part of glucocorticoids effects on these behaviors may mediate through NMDA receptors suggesting an involvement of non-genomic mechanisms. Our findings suggest a potential role for glucocorticoid receptors agonist in combination of NMDA receptors antagonists in clinical management of neuropathic pain.