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.

Keywords: galanin; galanin receptors; nociception; pain.

Figure 1

Flowchart representation of the different stages of the selection process.

Figure 2

Mechanism of action of galanin in chronic pain conditions. Under normal situations, peripheral nerve injury or inflammation induces an increase in galanin levels that act upon GalR1 receptors, inhibiting nociceptive transmission. In chronic pain conditions, there is an upregulation of GalR2 receptors in peripheral nerve afferents and their correspondent dorsal root ganglia (DRG), which causes hypersensitivity to noxious stimulation and consequent mechanical and thermal hyperalgesia. Peripheral injury was also shown to increase galanin levels at both a spinal and supraspinal level, and its administration produces an antinociceptive effect upon nociceptive processing. (ACC—anterior cingulate cortex; ARC—arcuate nucleus of the hypothalamus; CeA—central nucleus of the amygdala; LHb—lateral habenula; NAc—nucleus accumbens; PAG—periaqueductal gray; RVM—rostral ventromedial medulla; SDH—spinal dorsal horn). Created in BioRender.com.