Emerging Trends in Pain Modulation by Metabotropic Glutamate Receptors.

Vanessa Pereira,Cyril Goudet

doi:10.3389/fnmol.2018.00464

Abstract

Pain is an essential protective mechanism meant to prevent tissue damages in organisms. On the other hand, chronic or persistent pain caused, for example, by inflammation or nerve injury is long lasting and responsible for long-term disability in patients. Therefore, chronic pain and its management represents a major public health problem. Hence, it is critical to better understand chronic pain molecular mechanisms to develop innovative and efficient drugs. Over the past decades, accumulating evidence has demonstrated a pivotal role of glutamate in pain sensation and transmission, supporting glutamate receptors as promising potential targets for pain relieving drug development. Glutamate is the most abundant excitatory neurotransmitter in the brain. Once released into the synapse, glutamate acts through ionotropic glutamate receptors (iGluRs), which are ligand-gated ion channels triggering fast excitatory neurotransmission, and metabotropic glutamate receptors (mGluRs), which are G protein-coupled receptors modulating synaptic transmission. Eight mGluRs subtypes have been identified and are divided into three classes based on their sequence similarities and their pharmacological and biochemical properties. Of note, all mGluR subtypes (except mGlu6 receptor) are expressed within the nociceptive pathways where they modulate pain transmission. This review will address the role of mGluRs in acute and persistent pain processing and emerging pharmacotherapies for pain management.

Highlights

Acute pain is an important protective function, detecting harmful stimuli and preventing body damage
Patients suffering from chronic pain experience exacerbated responses to both painful and non-painful stimuli (Sandkühler, 2009) and frequently express emotional and cognitive impairments often resulting in anxiety and depression (McWilliams et al, 2003; Moriarty et al, 2011; Bushnell et al, 2013)
The growing number of selective compounds for the different metabotropic glutamate receptors (mGluRs) has significantly improved our understanding of the specific role of each subtype in nociception

Summary

Introduction

Acute pain is an important protective function, detecting harmful stimuli and preventing body damage. MGlu1 receptor inhibition relieves both mechanical and thermal hypersensitivity in various models of both inflammatory and neuropathic pain (Table 1) (Varty et al, 2005; El-Kouhen et al, 2006; Sevostianova and Danysz, 2006; Satow et al, 2008; Zhu et al, 2008).

Results

Conclusion