A New Gal in Town: A Systematic Review of the Role of Galanin and Its Receptors in Experimental Pain

Abstract

Galanin is a neuropeptide expressed in a small percentage of sensory neurons of the dorsal root ganglia and the superficial lamina of the dorsal horn of the spinal cord. In this work, we systematically reviewed the literature regarding the role of galanin and its receptors in nociception at the spinal and supraspinal levels, as well as in chronic pain conditions. The literature search was performed in PubMed, Web of Science, Scopus, ScienceDirect, OVID, TRIP, and EMBASE using “Galanin” AND “pain” as keywords. Of the 1379 papers that were retrieved in the initial search, we included a total of 141 papers in this review. Using the ARRIVE guidelines, we verified that 89.1% of the works were of good or moderate quality. Galanin shows a differential role in pain, depending on the pain state, site of action, and concentration. Under normal settings, galanin can modulate nociceptive processing through both a pro- and anti-nociceptive action, in a dose-dependent manner. This peptide also plays a key role in chronic pain conditions and its antinociceptive action at both a spinal and supraspinal level is enhanced, reducing animals’ hypersensitivity to both mechanical and thermal stimulation. Our results highlight galanin and its receptors as potential therapeutic targets in pain conditions.

Behavioral characterization of G-protein-coupled receptor 160 knockout mice

“…42,43 Cocaineand amphetamine-regulated transcript peptide is found primarily in peptidergic C fibers that innervate laminae I-II of the dorsal horn of the spinal cord and colocalize with calcitonin gene-related peptide (CGRP), galanin, and substance P, important neuropeptides involved in pain processing and neuropathic pain states. 28,37,54 To the best of our knowledge, whether CARTp has a functional role in PNS sensitization has not been examined.…”

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

“…It also has been shown to induce cell death in pheochromocytoma cells (86). Importantly, the role of galanin in pain has been reported to have pro-and anti-nociceptive functions and whether or not galanin plays a role in peripheral nociceptive mechanisms is yet to be confirmed (87). Interestingly, galanin release from sensory neurons have been shown to promote oral cancer progression (88).…”

Role of neuropeptides in orofacial pain: A literature review

“…According to the experiment of GalR3 gene-deficient mice, GAL played an anti-inflammatory role by acting on GalR3, inhibiting vascular permeability, plasma exosmosis, and subsequent edema formation. 11 On the other hand, GAL can also act directly on various immune inflammatory cells, inhibiting the expression of pro-inflammatory cytokines. GAL-IR nerve fibres are present in the vicinity of macrophages and dendritic cells with GAL-immunoreactivity.…”

“…On the one hand, the anti‐inflammatory effect of GAL can be achieved by acting on blood vessels. According to the experiment of GalR3 gene‐deficient mice, GAL played an anti‐inflammatory role by acting on GalR3, inhibiting vascular permeability, plasma exosmosis, and subsequent edema formation 11 . On the other hand, GAL can also act directly on various immune inflammatory cells, inhibiting the expression of pro‐inflammatory cytokines.…”

“…8 After sensory neurons are stimulated, neuropeptides are released from nerve terminals or synaptic clefts and act directly on neurons (nociceptors, TG, and SpVc) or non-neuronal targets (glial cells, endothelial cells and inflammatory cells), thereby contributing to neurogenic inflammation and orofacial pain. Previous studies have demonstrated that neuropeptides, including calcitonin generelated peptide (CGRP), 4 substance P (SP), 9 opioid peptides (OP), 10 galanin (GAL), 11 vasoactive intestinal peptide (VIP), 12 neuropeptide Y (NPY), 13 neurokinin A (NKA), 14 orexin-A (OrxA) 15 and oxytocin (OXT), 16 are involved in orofacial pain. Studies have shown that different neuropeptides exert distinct effects (hyperalgesic or analgesic) in orofacial pain through diverse mechanisms.…”