Department of Anesthesiology, School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto, 860-8556, Japan.
Department of Anesthesiology, School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto, 860-8556, Japan.
Peptides. 2019 May;115:1-7. doi: 10.1016/j.peptides.2019.02.003. Epub 2019 Feb 14.
26RFa is an endogenous ligand for the QRFP receptor. We previously found that intracerebroventricular injection of 26RFa produces an analgesic effect in a rat formalin test. In the present study, we directly tested the hypothesis that the analgesic effects of 26RFa in the formalin test are mediated in well-recognized regions of the descending inhibitory pain pathways, such as the rostral ventromedial medulla (RVM), locus coeruleus (LC), and periaqueductal grey (PAG) in rats. Injection cannulae were stereotaxically placed in the RVM, LC, or PAG through a burr hole. 26RFa (15 μg) or saline was delivered in a total volume of 0.5 μL. In a formalin test, 50 μL of 5% formalin was injected subcutaneously into the hind paw. In an antagonist study, idazoxan, an α-2 antagonist, or naloxone, an opioid receptor antagonist, was administered. Microinjection of 26RFa into the RVM had no effect compared with that in saline-injected rats. Microinjection of 26RFa into the LC contralateral, but not ipsilateral, to the formalin injection site significantly decreased the number of flinching behaviors compared with that of saline-injected rats. This effect was antagonized by intrathecal injection of idazoxan. Microinjection of 26RFa into the contralateral, but not ipsilateral, PAG produced an analgesic effect, and this effect was partly antagonized by intraperitoneal naloxone. These data suggest that 26RFa microinjected into the contralateral LC induced noradrenaline release in the spinal cord and produced an analgesic effect. In the contralateral PAG, 26RFa activated the opioid system, and some analgesic effects were mediated by opioid system activation.
26RFa 是 QRFP 受体的内源性配体。我们之前发现，脑室内注射 26RFa 可在大鼠福尔马林试验中产生镇痛作用。在本研究中，我们直接测试了以下假设，即 26RFa 在福尔马林试验中的镇痛作用是通过大鼠中已知的下行抑制性疼痛通路的区域介导的，例如腹内侧前脑（RVM）、蓝斑（LC）和中脑导水管周围灰质（PAG）。通过颅骨钻孔将注射套管立体定向放置在 RVM、LC 或 PAG 中。将 26RFa（15μg）或盐水以 0.5μL 的总体积递送至。在福尔马林试验中，将 50μL 5%福尔马林皮下注射到后爪。在拮抗剂研究中，给予伊达唑兰（α-2 拮抗剂）或纳洛酮（阿片受体拮抗剂）。与盐水注射大鼠相比，26RFa 注射到 RVM 中没有效果。与福尔马林注射部位同侧相比，26RFa 注射到 LC 的对侧显著减少了畏缩行为的数量。这种作用被鞘内注射伊达唑兰拮抗。与同侧相比，26RFa 注射到对侧 PAG 产生了镇痛作用，这种作用部分被腹腔内纳洛酮拮抗。这些数据表明，注射到对侧 LC 的 26RFa 诱导脊髓中的去甲肾上腺素释放，并产生镇痛作用。在对侧 PAG 中，26RFa 激活了阿片系统，并且一些镇痛作用是通过阿片系统激活介导的。
