Inflammatory and Neuropathic Nociception is Preserved in GPR55 Knockout Mice

Lawrence M. Carey,Andrea G. Hohmann,Liting Deng,Wan-Hung Lee,Ken Mackie,Tannia Gutierrez

doi:10.1038/s41598-017-01062-2

Lawrence M. Carey, Andrea G. Hohmann + Show 4 more

Open Access

https://doi.org/10.1038/s41598-017-01062-2

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Abstract

The G-protein coupled receptor GPR55 has been postulated to serve as a novel cannabinoid receptor. A previous report indicated that GPR55 knockout mice fail to develop mechanical hyperalgesia, suggesting a pro-nociceptive role for GPR55 in the control of nociceptive responding. However, GPR55 knockout mice remain incompletely characterized in models of pathological pain. Here we provide a comprehensive assessment of responses of GPR55 knockout and wild-type mice to mechanical and thermal (heat, cold) stimulation in multiple, mechanistically distinct models of inflammatory and neuropathic pain. Inflammatory sensitization was produced by intraplantar administration of capsaicin, formalin or complete Freund’s adjuvant. No differences in responding were detected between GPR55 knockout and wild-type mice in any model of inflammatory nociception assessed. Neuropathic pain was induced by partial sciatic nerve ligation (which induces hypersensitivity to mechanical, cold and heat stimulation) or by treatment with the chemotherapeutic agent paclitaxel (which induces hypersensitivity to mechanical and cold stimulation only). No differences were observed between GPR55 knockout and wild type mice in either development or maintenance of neuropathic nociception in either neuropathic pain model. In conclusion, genetic deletion of GPR55 did not alter the development of pathological pain in adult mice in any chronic pain model evaluated.

Highlights

GPR55 is expressed broadly, though at quite low levels throughout the CNS3, 10, and in large diameter dorsal root ganglion neurons[11], where GPR55 agonists promote increases in Ca+2 release from intracellular stores
The pungent ingredient in hot chili peppers, is a transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist and produces nocicfensive behavior and heat hypersensitivity, both of which are associated with peripheral sensitization, as well as mechanical hypersensitivity which is associated with central sensitization and secondary hyperalgesia[12, 13]
We evaluated GPR55 KO and WT mice in mechanistically distinct models of neuropathic pain including a model of chemotherapy-induced neuropathic pain induced by paclitaxel treatment and a model of traumatic nerve injury induced by PSNL8

Summary

Introduction

GPR55 is expressed broadly, though at quite low levels throughout the CNS3, 10, and in large diameter dorsal root ganglion neurons[11], where GPR55 agonists promote increases in Ca+2 release from intracellular stores. Based largely upon this report, GPR55 is postulated to be inherently nociceptive because GPR55 KO mice display an analgesic phenotype (i.e. fail to develop mechanical hypersensitivity to inflammatory and neuropathic pain)[8] For this reason, the present study sought to further characterize the profile of nociceptive behaviors in GPR55 KO mice by measuring responsiveness of these mice to multiple modalities of cutaneous stimulation (mechanical, cold and heat) in a battery of mechanistically distinct inflammatory (induced by formalin, capsaicin and CFA) and neuropathic (induced by traumatic nerve injury and chemotherapy treatment) pain states. Our findings suggest that genetic deletion of GPR55 does not markedly alter the development or maintenance of inflammatory or neuropathic pain in adult mice tested in mechanistically distinct models of pathological pain with a wide array of cutaneous (mechanical, cold, heat) stimuli

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