Activation of GPR173 Alleviates Neuropathic Pain and Chronic Inflammation

Abstract

Neuropathic pain (NP) refers to pains induced by injury or disease involving the somatosensory system, which severely threatens physical and mental health of patients. Although pathogenesis of NP is uncertain, evidence has been provided for involvement of inflammation and oxidative stress (OS) in NP. G protein-coupled receptor (GPR173) is a converted GPCR, with Phoenixin 14 (PHN-14) as its ligand. Recent studies have revealed the neuroprotective property of PHN-14. Our study explored pharmacological effect of PHN-14 on NP. A chronic constriction injury (CCI) model was established in rats, followed by administering 60 mg/kg PHN-14 and 10 mg/kg pregabalin daily. As expected, the Gpr173 was downregulated in CCI rats. Reduced PWMT and PWTL values, increased serum potassium levels, and elevated serum C-reactive protein (CRP) and Calcitonin gene-related peptide (CGRP) levels were all observed in the CCI rats, all of which were significantly rescued by PHN-14 and pregabalin. Moreover, elevated malondialdehyde (MDA) and catalase (CAT) levels, repressed superoxide dismutase (SOD) activity, and upregulated Nrf2 perceived in CCI rats were abolished by PHN-14 and pregabalin. Lastly, the high levels of inflammatory mediators and activated NF-κB signaling in the CCI rats were greatly suppressed by PHN-14 and pregabalin. Collectively, the NP and chronic inflammation in CCI rats were alleviated by PHN-14, which is an agonist of GPR173.