Galanin Receptor 2 Is Involved in Galanin-Induced Analgesic Effect by Activating PKC and CaMKII in the Nucleus Accumbens of Inflammatory Pain Rats.
Galanin Receptor 2 Is Involved in Galanin-Induced Analgesic Effect by Activating PKC and CaMKII in the Nucleus Accumbens of Inflammatory Pain Rats.
复制标题
Galanin受体2通过在炎症性疼痛大鼠的伏隔核中激活PKC和CAMKII参与了Galanin诱导的镇痛作用。
DOI：
10.3389/fnins.2020.593331
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发表时间：
2020
影响因子：
4.3
通讯作者：
Xu S
中科院分区：
文献类型：
--
作者：
Li M;Zhang X;Li C;Liu Y;Yang S;Xu S
据报道，甘丙肽通过激活甘丙肽受体（GALR）而具有镇痛作用。本研究旨在探讨GALR 2参与甘丙肽诱导的炎症大鼠镇痛效应及其在丘脑腹外侧核（NAc）的信号转导机制。采用角叉菜胶注射于大鼠左后足跖建立动物模型。结果表明，GALR 2拮抗剂M871可部分减弱甘丙肽对炎症大鼠NAc热刺激后缩足潜伏期（HWL）和机械刺激后缩足阈值（HWT）的增加。此外，GALR 2激动剂M1145延长了HWL和HWT，而M871阻断了M1145诱导的HWL和HWT增加。Western blotting结果显示，注射角叉菜胶后，NAc中钙/钙调素依赖性蛋白激酶II（p-CaMKII）和蛋白激酶C（p-PKC）的磷酸化水平上调，而注射M871后，NAc中p-PKC和p-CaMKII的磷酸化水平下调。此外，CaMKII抑制剂KN 93和PKC抑制剂GO 6983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GALR 2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GALR 2激动剂可能是炎性疼痛的有效治疗选择。
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.
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影响因子：
5.3
作者：
Baliki, Marwan N.;Mansour, Ali;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania
影响因子：
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作者：
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影响因子：
2.5
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Yu, Long-Chuan
影响因子：
3.7
作者：
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通讯作者：
Pinto-Ribeiro, Filipa