Catestatin is involved in neuropathic pain mediated by purinergic receptor P2X4 in the spinal microglia of rats

Abstract

Neuropathic pain is defined as a type of chronic pathological pain that often results from nerve damage or disease. The purinergic receptor P2X₄ is mainly expressed on the cell surface of spinal dorsal horn microglia and is known to be involved in neuropathic pain. Catestatin (CST) is an endogenous peptide derived from chromogranin A. Here, we attempted to identify how CST function in neuropathic pain. Rat model of chronic constriction injury (CCI) was used and experimental results indicated that mechanical and thermal pain sensitivities were significantly increased in CCI rats. The group of CCI rats that received intrathecal CST injection (CCI + CST) exhibited higher P2X₄ mRNA and protein levels compared with the CCI group. Moreover, the phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2) in the CCI + CST group was higher than in the CCI group. This suggested that CST might aggravate neuropathic pain by enhancing P2X₄ receptor expression in spinal microglia, and that the ERK1/2 pathway might be key in the development of neuropathic pain.

Keywords: Catestatin; Extracellular signal-regulated kinase 1/2; Microglia; Neuropathic pain; P2X(4)receptor; Spinal dorsal horn.