Sigma‑1 receptor regulates p‑PKCα and P2X3 expression in dorsal root ganglia to attenuate neuropathic pain in rats

Abstract

The present study aims to elucidate the role of the Sigma‑1 receptor in the pathogenesis of neuropathic pain and evaluate its potential therapeutic implications. To systematically assess the effects of the Sigma‑1 receptor, neuropathic pain was induced in rats using the chronic constriction injury (CCI) model. Subjects were subsequently divided into three groups: Sham, CCI, and CCI+BD1047 (where BD1047 is a Sigma‑1 receptor antagonist). Following intrathecal administration of the respective agents, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured. Additionally, Western blotting was utilized to examine Sigma‑1 receptor, phosphorylated protein kinase Cα (p‑PKCα), and P2X3 receptor expression in the dorsal root ganglia (DRG). Immunofluorescence techniques were employed to examine p‑PKCα and P2X3 receptor expression. The results indicate a direct correlation between Sigma‑1 receptor activity and pain perception, evidenced by changes in TWL and MWT. In the CCI group, both TWL and MWT were significantly reduced compared to the Sham group. Furthermore, protein levels of the Sigma‑1 receptor, p‑PKCα, and P2X3 receptor in the DRG were elevated, and immunofluorescence expression of p‑PKCα and the P2X3 receptor also increased. Conversely, in the CCI+BD1047 group, TWL and MWT were significantly enhanced. Additionally, protein levels of the Sigma‑1 receptor, p‑PKCα, and P2X3 receptor in the DRG decreased, along with reduced immunofluorescence expression of p‑PKCα and P2X3 receptor. The findings indicate that neuropathic pain is intricately associated with the Sigma‑1 receptor, p‑PKCα, and P2X3 receptor in the dorsal root ganglia. Notably, the Sigma‑1 receptor regulates the expression of p‑PKCα and P2X3 receptor, presenting a novel therapeutic target for neuropathic pain management.