Increased Na _v 1.7 expression in the dorsal root ganglion contributes to pain hypersensitivity after plantar incision in rats

Abstract

Postoperative pain remains a complex problem that is difficult to manage in the clinical context, seriously affecting rehabilitation and the quality of life of patients after surgery. Nociceptors, of which the cell bodies are located in the dorsal root ganglion, are crucial for initiating and conducting the pain signal. The peripheral voltage-gated sodium channels, including Na v 1.7, which is mainly expressed in the dorsal root ganglion, are key to understanding the mechanism underlying postoperative pain. Na v 1.7, in particular, of which mutations in the encoding gene ( SCN9A) can determine whether pain occurs, has aroused most attention. Previous studies have shown that Na v 1.7 in dorsal root ganglion is critical for the development of inflammatory pain and some neuropathic pain. However, the expression of Na v 1.7 in the dorsal root ganglion after surgery and its role in postoperative pain hypersensitivity remain unclear. Therefore, in this study, in order to gain a better understanding of the role of dorsal root ganglion Na v 1.7 in pain hypersensitivity following operation, we dynamically examined the pain-related behavior and expression of Na v 1.7 in L4−L6 dorsal root ganglion before and after plantar incision in rats (an acute postoperative pain model). After plantar incision, the mechanical and thermal pain threshold decreased significantly, the cumulative pain score was increased significantly, meanwhile quantitative polymerase chain reaction and Western blotting results showed that expression of Na v 1.7 in L4−L6 dorsal root ganglion was enhanced significantly. After pretreatment using SCN9A-RNAi-LV delivered via an intrathecal tube, immunohistochemistry showed that increased expression of Na v 1.7 in L4−L6 dorsal root ganglion after plantar incision was inhibited, as also confirmed by quantitative polymerase chain reaction and Western blotting. Moreover, pain hypersensitivity was alleviated. These results suggested that Na v 1.7 of L4−L6 dorsal root ganglion plays an important role in the development of pain hypersensitivity after plantar incision.