Role of P2X3 receptors in development and maintenance of neuropathic pain in rats: the relationship with NF-κB in dorsal root ganglia

Objective To evaluate the role of P2X3 receptors in the development and maintenance of neuropathic pain(NP)and the relationship with nuclear factor kappa B(NF-κB)in dorsal root ganglia of rats. Methods Thirty-six SPF healthy male Sprague-Dawley rats, weighing 180-200 g, aged 4-6 weeks, in which intrathecal catheters were successfully implanted, were divided into 3 groups(n=12 each)using a random number table: sham operation group(group S), NP group and P2X3 receptor antagonist A-317491 group(group A). At 3 days after intrathecal catheters were successfully implanted, NP was induced by chronic constriction injury to the sciatic nerve.The sciatic nerve was only exposed but not occluded in group S. Intrathecal injection was performed twice a day for 14 consecutive days starting from 1 day after operation.Normal saline 20 μl was intrathecally injected in group S and group NP, and A-317491 100 nmol/10 μl and normal saline 10 μl were intrathecally injected in group A. Thermal paw withdrawal threshold(TWT)and mechanical paw withdrawal threshold(MWT)were measured on day 1 before operation and at 30 min after intrathecal injection on days 1, 3, 7, 10 and 14 after operation.On days 7 and 14 after operation, the rats were sacrificed and the dorsal root ganglia of the lumbar segment were removed for determination of the expression of P2X3 receptors and NF-κB p65 by Western blot. Results Compared with group S, TWT and MWT were significantly decreased at each time point after operation, and the expression of P2X3 receptors and NF-κB p65 in dorsal root ganglia was up-regulated on days 7 and 14 after operation in group NP(P<0.05 or 0.01). Compared with group NP, TWT was significantly increased at each time point after operation, MWT was increased on days 3, 7, 10 and 14 after operation, and the expression of P2X3 receptors and NF-κB p65 in dorsal root ganglia was down-regulated on days 7 and 14 after operation in group A(P<0.05). Conclusion The mechanism underlying the development and maintenance of NP is related to the up-regulation of P2X3 receptor expression and promotion of the expression of NF-κB in dorsal root ganglia of rats. Key words: Neuropathic pain; Dorsal root ganglion; P2X3 receptor; NF-κB