The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain

Yan Dong,Shi-Lian Xu,Ya-Nan Liu,Chong-Yang Li,Meng-Nan Li,Shuang Yang,Xiao-Min Zhang

doi:10.1186/s12576-021-00790-5

Yan Dong, Shi-Lian Xu + Show 5 more

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https://doi.org/10.1186/s12576-021-00790-5

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Abstract

Our previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

Highlights

Neuralgia is a chronic pain which deteriorates the quality of life of patients severely
The results suggest that GalR2 agonist M1145 has an antinociceptive effect by activating GalR2 in the nucleus accumbens (NAc) of constriction injury of sciatic nerve (CCI)
The results of this study showed that the expression of GalR2 was significantly up-regulated in bilateral NAc of rats after CCI (Fig. 1), and the intra-NAc injection of GalR2 antagonist M871 attenuated the galanin-induced increases in hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal thresh‐ old (HWT) to mechanical stimulation in CCI rats (Fig. 2), while the GalR2 agonist M1145 increased the HWL and HWT (Fig. 3)

Summary

Introduction

Neuralgia is a chronic pain which deteriorates the quality of life of patients severely. The effective treatment of Neuralgia is lacking because of its complex pathogenesis. Analgesics such as N-methyl-D-aspartic acid (NMDA) receptor antagonists, sodium channel blockers, especially opioid analgesics are used to alleviate neuropathic pain, but the severe side effects have greatly limited their universal use. An early study showed that intense chemical or thermal noxious stimulation-induced pain perception was Galanin is widely distributed in the central nervous system (CNS) and peripheral tissues with multiple biological functions. Studies showed that exogenous galanin had an antinociceptive effect in central nucleus of the amygdala [7] and the anterior cingulate cortex (ACC) [8] in normal

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