Li Mengnan, Zhang Xiaomin, Li Chongyang, Liu Yanan, Yang Shuang, Xu Shilian
Department of Physiology, School of Basic Medicine, Kunming Medical University, Kunming, China.
Department of Oncology, Affiliated Hospital, Yunnan University, Kunming, China.
Front Neurosci. 2021 Jan 21;14:593331. doi: 10.3389/fnins.2020.593331. eCollection 2020.
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.
据报道，甘丙肽通过激活甘丙肽受体（GALRs）发挥镇痛作用。本研究聚焦于GALR2在甘丙肽诱导的镇痛效应中的作用及其在炎性大鼠伏隔核（NAc）中的信号传导机制。通过向大鼠左后爪足底注射角叉菜胶建立动物模型。结果显示，GALR2拮抗剂M871部分削弱了甘丙肽诱导的炎性大鼠NAc中热刺激后爪退缩潜伏期（HWL）和机械刺激后爪退缩阈值（HWT）的增加。此外，GALR2激动剂M1145延长了HWL和HWT，而M871阻断了M1145诱导的HWL和HWT的增加。蛋白质印迹法显示，注射角叉菜胶后NAc中钙/钙调蛋白依赖性蛋白激酶II（p-CaMKII）和蛋白激酶C（p-PKC）的磷酸化上调，而在NAc内注射M871后p-PKC和p-CaMKII下调。此外，CaMKII抑制剂KN93和PKC抑制剂GO6983减弱了M1145诱导的炎性疼痛大鼠NAc中HWL和HWT的增加。这些结果证明，GALR2通过激活炎性疼痛大鼠NAc中的CaMKII和PKC参与甘丙肽诱导的镇痛作用，这意味着GALR2激动剂可能是炎性疼痛的有效治疗选择。
