Abstract
It has been reported that galanin has an analgesic effect via activating galanin receptors (GALRs). This study focused on the involvement of GALR2 in the galanin-induced analgesic effect and its signaling mechanism in the nucleus accumbens (NAc) of inflammatory rats. Animal models were established through injecting carrageenan into the plantar of rats’ left hind paw. The results showed that GALR2 antagonist M871 weakened partially the galanin-induced increases in hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation in NAc of inflammatory rats. Moreover, the GALR2 agonist M1145 prolonged the HWL and HWT, while M871 blocked the M1145-induced increases in HWL and HWT. Western blotting showed that the phosphorylation of calcium/calmodulin-dependent protein kinase II (p-CaMKII) and protein kinase C (p-PKC) in NAc were upregulated after carrageenan injection, while p-PKC and p-CaMKII were downregulated after intra-NAc administration of M871. Furthermore, the CaMKII inhibitor KN93 and PKC inhibitor GO6983 attenuated M1145-induced increases in HWL and HWT in NAc of rats with inflammatory pain. These results prove that GALR2 is involved in the galanin-induced analgesic effect by activating CaMKII and PKC in NAc of inflammatory pain rats, implying that GALR2 agonists probably are potent therapeutic options for inflammatory pain.
Highlights
Pain is a dominating feature of inflammation, but the underlying mechanisms of inflammatory pain resolution are not fully understood
GALR2 was upregulated in nucleus accumbens (NAc) 3 h after injection of carrageenan (Yang et al, 2015). To explore whether this analgesic effect was mediated by GALR2, 3 h after carrageenan injection, two groups of inflammatory pain rats received an intra-NAc injection of 2 nmol galanin followed by an intra-NAc injection of 2 nmol GALR2 antagonist M871 (n = 8) or 1 μl of 6% acetonitrile as a control (n = 9) 5 min later
Compared to the group treated with galanin + acetonitrile, galanin-induced increases in hind paw withdrawal latency (HWL) to thermal stimulation (Left hind paw: F(1,75) = 9.48, P = 0.0076; Right hind paw: F(1,75) = 5.246, P = 0.0369) and hind paw withdrawal threshold (HWT) to mechanical stimulation [Left hind paw: F(1,75) = 4.551, P = 0.0498; Right hind paw: F(1,75) = 6.366, P = 0.0234] were effectively blocked by the intra-NAc injection of GALR2 antagonist M871
Summary
Pain is a dominating feature of inflammation, but the underlying mechanisms of inflammatory pain resolution are not fully understood. Our studies showed that intra-nucleus accumbens (NAc) administration of galanin increased the HWLs in rats (Xu S.L. et al, 2012; Yang et al, 2015; Zhang et al, 2019). It has been demonstrated that galantide, a nonselective GALRs antagonist, attenuates galanin-induced analgesic effect in rats (Xu S.L. et al, 2012; Yang et al, 2015). The GALR2-specific agonist M1145 (Runesson et al, 2009; Saar et al, 2013) and the GALR2-specific antagonist M871 (Sollenberg et al, 2006) were used to investigate the analgesic effect of GALR2 in rats with inflammatory pain. We hope to provide a new insight into the treatment of inflammatory pain
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