Low-dose ketamine inhibits expression of P2X_4 receptor in spinal dorsal horn of rats with chronic neuropathic pain

Objective:To observe the effect intraperitoneal injection of low dose ketamine on thermal hyperalgesia and expression of P2X4 receptor in spinal dorsal horn of rats with chronic constriction injury (CCI) of sciatic nerve,and to explore the potential role of P2X4 receptor in the neuropathic pain.Methods:Totally 24 Sprague-Dawley rats were randomly divided into 3 groups (n=8):group S (sham group),group C:CCI + normal saline; and group K:CCI+ketamine (10 mg·kg-1).Rat CCI model was used in the latter 2 groups.Three days after operation the thermal withdrawal latency (TWL) was determined to confirm the thermal hyperalgesia.Rats in group K were given low dose of ketamine (10 mg·kg-1)and those in group C were given the same volume of normal saline for 7 days after operation.Animals in group S only had sciatic nerve exposed,with no ligation or drugs.TWL was determined 1 day before and 1,3,7 days after the operation.The expression of P2X4 receptor was assessed 7 days after the operation using immunohistochemistry.Results:The TWL values were similar between the 3 groups before operation.The value in group S was slightly decreased after operation compared with before operation.Compared with the pre-operation,group S,and group C,the TWL value of group K began to gradually increase 3 days after operation till day 7 after operation(P0.05).On day 7 after operation,the TWL value was significantly higher than group C (P0.05),but was still lower than that in group S (P0.05).Immunohistochemistry showed that the expression of P2X4 receptor in group C,K were significantly higher than that of group S (P0.01),and the expression in group K was significantly lower than that in group C(P0.05).Conclusion:Intraperitoneal injection of ketamine can partly relieve the thermal hyperalgesia in rats with CCI of sciatic nerve,which might be related to the inhibition of P2X4 receptor expression in the spinal dorsal horn.