Department of Clinical and Molecular Biomedicine, University of Catania, Italy.
Mol Pain. 2011 Nov 23;7:90. doi: 10.1186/1744-8069-7-90.
Kisspeptin is a neuropeptide known for its role in the hypothalamic regulation of the reproductive axis. Following the recent description of kisspeptin and its 7-TM receptor, GPR54, in the dorsal root ganglia and dorsal horns of the spinal cord, we examined the role of kisspeptin in the regulation of pain sensitivity in mice.
Immunofluorescent staining in the mouse skin showed the presence of GPR54 receptors in PGP9.5-positive sensory fibers. Intraplantar injection of kisspeptin (1 or 3 nmol/5 μl) induced a small nocifensive response in naive mice, and lowered thermal pain threshold in the hot plate test. Both intraplantar and intrathecal (0.5 or 1 nmol/3 μl) injection of kisspeptin caused hyperalgesia in the first and second phases of the formalin test, whereas the GPR54 antagonist, p234 (0.1 or 1 nmol), caused a robust analgesia. Intraplantar injection of kisspeptin combined with formalin enhanced TRPV1 phosphorylation at Ser800 at the injection site, and increased ERK1/2 phosphorylation in the ipsilateral dorsal horn as compared to naive mice and mice treated with formalin alone.
These data demonstrate for the first time that kisspeptin regulates pain sensitivity in rodents and suggest that peripheral GPR54 receptors could be targeted by novel drugs in the treatment of inflammatory pain.
kisspeptin 是一种神经肽，已知在调节下丘脑生殖轴方面发挥作用。最近在背根神经节和脊髓背角描述了 kisspeptin 及其 7-TM 受体 GPR54 后，我们研究了 kisspeptin 在调节小鼠疼痛敏感性中的作用。
在小鼠皮肤中的免疫荧光染色显示 GPR54 受体存在于 PGP9.5 阳性感觉纤维中。足底内注射 kisspeptin（1 或 3 nmol/5 μl）可诱导未处理小鼠产生小的伤害性反应，并降低热板试验中的热痛阈值。足底内和鞘内（0.5 或 1 nmol/3 μl）注射 kisspeptin 均可引起福尔马林试验的第一和第二阶段的痛觉过敏，而 GPR54 拮抗剂 p234（0.1 或 1 nmol）则引起强烈的镇痛作用。与单纯注射福尔马林的小鼠相比，足底内注射 kisspeptin 可增强注射部位 TRPV1 在 Ser800 处的磷酸化，并增加同侧背角中 ERK1/2 的磷酸化。
这些数据首次表明 kisspeptin 调节啮齿动物的疼痛敏感性，并提示外周 GPR54 受体可能成为治疗炎症性疼痛的新型药物的靶点。
