Role of TLR4/NF-κB signaling pathway in development of postoperative chronic pain in rats: the relationship with expression of Nav1.7 in dorsal root ganglion

Abstract

Objective To evaluate the role of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in the development of postoperative chronic pain and the relationship with expression of voltage-gated sodium channel 1.7(Nav1.7)in the dorsal root ganglion (DRG) of rats. Methods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 9-11 weeks, weighing 200-250 g, were divided into 3 groups (n=12 each) using a random number table method: control group (group C), normal saline group (group NS) and TLR4 antagonist LPS-RS group (group R). Postoperative chronic pain was produced by skin/muscle incision and retraction (SMIR). From 1 day before SMIR to 10 days after SMIR, NS group received continuous intrathecal injection of normal saline 10μl, while R group received continuous intrathecal injection of LPS-RS 20 μg/10 μl.Six rats were randomly selected in each group, and the mechanical pain threshold was measured at 1 day before SMIR and 1, 5, 10, 15 and 20 days after SMIR.The 6 rats left in each group were sacrificed at day 10 after SMIR, and the DRGs of the lumbar segment (L4, 5) were removed for determination of the expression of phosphorylated NF-κB (p-NF-κB) and Nav1.7. Results Compared with group C, the mechanical pain threshold was significantly decreased at 5-20 days after SMIR, and the expression of p-NF-κB and Nav1.7 was up-regulated at 10 days after SMIR in group NS (P<0.01). Compared with group NA, the mechanical pain threshold was significantly increased at 5-20 days after SMIR, and the expression of p-NF-κB and Nav1.7 was down-regulated at 10 days after SMIR in group R (P<0.01). Conclusion Up-regulated expression of Nav1.7 in DRGs after activating TLR4/NF-κB signaling pathway is involved in the development of postoperative chronic pain in rats. Key words: Toll-like receptor 4; NF-kappa B; Pain, postoperative; Ganglia, spinal; Sodium channels