Effect of doxepin on expression of p38MAPK in spinal cord of rats with neuropathic pain

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. Key words: Doxepin; Neuralgia; p38 Mitogen-activated protein kinases; Spinal cord