Department of Physiology, School of Basic Medicine, Kunming Medical University, Kunming, China.
Physiol Res. 2019 Jun 30;68(3):511-518. doi: 10.33549/physiolres.933941. Epub 2019 Mar 22.
Galanin and galanin receptors (GalRs) have been reported to be involved in the transmission and modulation of nociceptive information in the central nervous system (CNS). However, the underlying mechanism of the antinociception of GalRs in neuropathic pain remains unclear. This study investigated the antinociception induced by galanin receptor 1 (GalR1) via protein kinase A (PKA) signaling pathway in the nucleus accumbens (NAc) of rats with neuropathic pain. A mononeuropathy model was replicated by ligation of the left sciatic nerve, following which the expression of phospho-PKA (p-PKA) in the NAc were markedly up-regulated at 14(th) and 28(th) day after ligation of sciatic nerve, and p-PKA expression was down-regulated by intra-NAc injection of GalR1 agonist M617, but the GalR1 antagonist M35 did not have an effect. We also found that M35 in the NAc blocked the M617-induced increase in the hind paw withdrawal latencies (HWLs) of rats with mononeuropathy, but M35 alone had no effect on HWLs, and PKA inhibitor H-89 attenuated the M617-induced an increase in the HWLs. These results suggested that GalR1 induced an antinociception via inhibiting PKA activation, implying that GalR agonists may be potential and potent therapeutic options to treat chronic neuropathic pain.
甘丙肽和甘丙肽受体（GalRs）已被报道参与中枢神经系统（CNS）中痛觉信息的传递和调制。然而，GalRs 在神经病理性疼痛中的镇痛作用的潜在机制尚不清楚。本研究通过蛋白激酶 A（PKA）信号通路研究了神经病理性疼痛大鼠伏隔核（NAc）中甘丙肽受体 1（GalR1）的镇痛作用。通过结扎左侧坐骨神经复制单神经病模型，结扎坐骨神经后 14 天和 28 天，NAc 中磷酸化 PKA（p-PKA）的表达明显上调，NAc 内注射 GalR1 激动剂 M617 可下调 p-PKA 表达，但 GalR1 拮抗剂 M35 没有作用。我们还发现，NAc 中的 M35 阻断了 M617 诱导的单神经病大鼠后爪退缩潜伏期（HWL）的增加，但 M35 本身对 HWL 没有影响，PKA 抑制剂 H-89 减弱了 M617 诱导的 HWL 增加。这些结果表明，GalR1 通过抑制 PKA 激活诱导镇痛作用，表明 GalR 激动剂可能是治疗慢性神经病理性疼痛的潜在有效治疗选择。
