The effect of systemic administration of gabapentin on the expression of toll-like receptor 4 in dorsal root ganglion neurons in diabetic neuropathic pain rats

Abstract

Objective To investigate the effect of systemic administration of gabapentin(GBP) on the expression of toll-like receptor 4(TLR4) in dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP).Methods One hundred and eight male SD rats weighing 200 g-220 g were randomly divided into 4 groups (n=27):control group (group C),DNP group,saline group (SC+DNP group)and gabapentin group(GBP+DNP group).Diabetes was induced with streptozocin(70 mg/kg) subcutaneously.Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured at 1 d before and 3,7,10,14,21,28 d after streptozocin injection and 21,28 d after administration of GBP (50 mg/kg,once)intraperitoneally.Saline and GBP (50 mg/kg) were given intraperitoneally once a day for 7 days starting from 15 d after streptozocin injection in saline and GBP groups respectively.The expression of TLR4 was determined at 21 d after streptozocin injection by immune.Histochemistry and Western blot.Results Compared with group C,PWMT (3.9 ±0.9) was significantly decreased,PWTL [(6.1 ±0.8) s]was significantly shorten,TLR4 in expression was significantly increased in DNP,SC+DNP group and GBP+DNP group (P＜0.05).Compared with SC+DNP group,PWMT(8.3±0.8)was significantly increased,PWTL[(9.9±1.2) s]was significantly prolonged,TLR4 expression was significantly decreased in GBP+DNP group (P＜0.05).There was no significant difference in the parameters mentioned above between DNP and SC+DNP group (P＞0.05).Conclusions Systemic administration of GBP attenuates diabetic neuropathic pain by inhibiting the expression of TLR4 in DRG neurons. Key words: Gabapentin; Diabetic neuropathic pain; Dorsal root ganglia; Toll-like receptor 4