GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats.

Ángel Zúñiga-Romero,Quetzali Rivera-Plata,Jesús Arrieta,Francisco Javier Flores-Murrieta,Gustavo Ramírez-Martínez,Juan Carlos Huerta-Cruz,Juan Gerardo Reyes-García,Héctor Isaac Rocha-González,Juan Rodríguez-Silverio

doi:10.3390/ph15010067

Abstract

Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.

Highlights

Published: 5 January 2022According to the IASP, neuropathic pain is defined as a pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system
Controls of GPR55 and GPR119 receptors in the processing of neuropathic pain induced by L5-L6 spinal nerve ligation in rats
L5-L6 spinal nerve ligation produced tactile allodynia in the ipsilateral left h

Summary

Introduction

According to the IASP, neuropathic pain is defined as a pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. 10% of the general population [1] and patients often experience bothersome symptoms as pain due to non-painful stimulations (allodynia) and an enhanced pain response (hyperalgesia). These symptoms frequently worsen and respond less to pharmacological treatment over time having a negative impact on quality of life [2].

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Discussion

Conclusion