Effect of PKC/NF-κB on the Regulation of P2X3 Receptor in Dorsal Root Ganglion in Rats with Sciatic Nerve Injury. (18th September 2020)

• Record Type: Journal Article
• Authors: Li, Xue; Yuan, Jie; Yu, Xuan; Zhang, Qin; Qin, Bangyong
• Other Names: Ablin Jacob Academic Editor.
• Is Part Of: Pain research and management. Volume 2020(2020)
• Publication Date: 2020-09-18
• Subjects: Pain -- Periodicals; Pain -- Treatment -- Periodicals; 616.0472
• DOI: 10.1155/2020/7104392
• Languages: English
• ISSNs: 1203-6765

Abstract

Abstract : Background . Protein kinase C (PKC), nuclear factor-kappa B p65 (NF- κ B p65), and P2X3 receptor (P2X3 R) play significant roles in the sensitization and transduction of nociceptive signals, which are considered as potential targets for the treatment of neuropathic pain. However, the mechanisms and relationships among them have not been clearly clarified. Methods . 80 rats were randomized and divided into 10 groups ( n = 8). Sciatic chronic constriction injury (CCI) rats were intrathecally administered with bisindolylmaleimide I (GF109203X), a PKC-selective antagonist once a day, or pyrrolidine dithiocarbamate (PDTC), an NF- κ B inhibitor twice a day. Sham-operated rats were intrathecally administered with saline. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were evaluated in all the groups before CCI operation (baseline) and on the 1st, 3rd, 7th, 10th, and 14th day after CCI operation. Protein levels of p-PKC α, p-NF- κ B p65, and P2X3 R were analyzed in the CCI ipsilateral L4–6 dorsal root ganglions (DRGs). Results . Intrathecal injection of GF109203X or PDTC alleviated the TWL and MWT in the following 2 weeks after CCI surgery. The protein levels of p-PKC α, p-NF- κ B p65, and P2X3 R in the ipsilateral DRGs significantly increased after CCI operation, which could be partly reversed by intrathecal administration of GF109203X or PDTC. Conclusion . The upregulation of p-PKC α, p-NF- κ B p65, and P2X3 R expression in the DRGs of CCI rats was involved in the occurrence and development of neuropathic pain. Phosphorylated PKC α and phosphorylated NF- κ B p65 regulated with each other. Phosphorylated NF- κ B p65 and PKC α have a mutual regulation relationship with P2X3 R, respectively, while the specific regulatory mechanism needs further research.