Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
Neuropeptides. 2022 Feb;91:102212. doi: 10.1016/j.npep.2021.102212. Epub 2021 Nov 20.
Orofacial pain is one of the most common medical challenges. A preliminary report indicates that the NOP receptor may act as a therapeutic target in orofacial pain. Previous studies have shown that [(pF)Phe, Aib, Aib, Arg, Lys]N/OFQ-NH (NOP01) functions as a potent NOP receptor peptide agonist. This work aims to investigate the antinociception of NOP01 and its possible action mechanisms in a formalin-induced mouse orofacial pain model at different levels. Our results demonstrated that local, intraperitoneal (i.p.) or intrathecal (i.t.) injection of NOP01 produced dose-related antinociception in both phases of the formalin pain, which could be inhibited by the NOP receptor antagonist but not the classical opioid receptor antagonist. Furthermore, the antinociception induced by systemic NOP01 was blocked by local but not spinal pretreatment with the NOP receptor antagonist, suggesting the involvement of the peripheral NOP receptor in NOP01-induced systemic antinociception. Moreover, local injection of NOP01 markedly suppressed the expression of c-Fos protein induced by formalin in ipsilateral trigeminal ganglion (TG) neurons. In conclusion, this work suggests that NOP01 exerts significant antinociception on orofacial pain at both peripheral and spinal levels via the NOP receptor. Notably, NOP01 cannot readily penetrate the blood-brain barrier. Thus, NOP01 may behave as a potential compound for developing peripherally restricted analgesics.
口腔颌面疼痛是最常见的医学挑战之一。初步报告表明，NOP 受体可能是口腔颌面疼痛的治疗靶点。先前的研究表明，[(pF)Phe、Aib、Aib、Arg、Lys]N/OFQ-NH（NOP01）作为一种有效的 NOP 受体肽激动剂发挥作用。本研究旨在探讨 NOP01 在福尔马林诱导的小鼠口腔颌面疼痛模型中的镇痛作用及其可能的作用机制。我们的研究结果表明，局部、腹腔内（i.p.）或鞘内（i.t.）注射 NOP01 在福尔马林疼痛的两个阶段均产生剂量依赖性镇痛作用，这种作用可被 NOP 受体拮抗剂而非经典阿片受体拮抗剂所抑制。此外，全身性 NOP01 诱导的镇痛作用被局部而非脊髓预处理 NOP 受体拮抗剂所阻断，提示外周 NOP 受体参与 NOP01 诱导的全身性镇痛作用。此外，局部注射 NOP01 可显著抑制福尔马林诱导的同侧三叉神经节（TG）神经元中 c-Fos 蛋白的表达。总之，本研究表明，NOP01 通过 NOP 受体对口腔颌面疼痛产生显著的镇痛作用，作用部位既包括外周也包括脊髓。值得注意的是，NOP01 不易穿透血脑屏障。因此，NOP01 可能是一种潜在的开发外周限制型镇痛药的化合物。
