Effect of doxepin on expression of p38MAPK in spinal cord of rats with neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of doxepin on the expression of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal cord of rats with neuropathic pain (NP).Methods Sixty clean-grade male Wistar rats in which intrathecal catheters were successfully implanted,weighing 200-250 g,were divided into 3 groups (n =20 each) by a random number table method:sham operation group (S group),NP group and doxepin group (D group).NP was induced by chronic constriction injury (CCI) to sciatic nerve.Doxepin 20 mmol/L (10 μl) was intrathecally injected at 3,7,14 and 21 days after CCI (T1-4) in group D.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (T0) and at T1-4.The rats were sacrificed after measurement of pain threshold at T4,and L4-6 segments of the spinal cord were removed for determination of the expression of p38MAPK protein by Western blot.Results Compared with S group,MWT was significantly decreased and TWL was shortened at T2-4,and the expression of p38MAPK protein was up-regulated in NP and D groups (P＜0.05).Compared with NP group,MWT was significantly increased and TWL was prolonged at T2-4,and the expression of p38MAPK protein was down-regulated in D group (P＜0.05).Conclusion The mechanism by which doxepin mitigates NP is related to down-regulating p38MAPK expression in the spinal cord of rats.