瞬时受体电位通道TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性和神经病理性疼痛模型中的镇痛作用(英文)

目的:评价瞬时受体电位通道(TRP通道)TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性、持续性和神经病理性疼痛模型中的作用。方法:通过辣椒素实验、异硫氰酸烯丙酯(AITC)实验和福尔马林实验,评估TRP通道拮抗剂在小鼠神经源性疼痛模型中的镇痛作用;通过建立紫杉醇诱导的小鼠神经病理性疼痛模型,对TRP通道拮抗剂的抗痛觉(冷、热、触觉)过敏效应进行评估;通过旋转法实验对小鼠的运动协调性进行评估。结论:TRP通道家族包含了不同的小鼠疼痛模型。TRP通道拮抗剂能减轻神经源性、持续性和神经病理性疼痛,但是其镇痛效果与疼痛模型有关。

Antinociceptive activity of transient receptor potential channel TRPV1, TRPA1, and TRPM8 antagonists in neurogenic and neuropathic pain models in mice

The aim of this research was to assess the antinociceptive activity of the transient receptor potential (TRP) channel TRPV1, TRPM8, and TRPA1 antagonists in neurogenic, tonic, and neuropathic pain models in mice. For this purpose, TRP channel antagonists were administered into the dorsal surface of a hind paw 15 min before capsaicin, allyl isothiocyanate (AITC), or formalin. Their antiallodynic and antihyperalgesic efficacies after intraperitoneal administration were also assessed in a paclitaxel-induced neuropathic pain model. Motor coordination of paclitaxel-treated mice that received these TRP channel antagonists was investigated using the rotarod test. TRPV1 antagonists, capsazepine and SB-366791, attenuated capsaicin-induced nociceptive reaction in a concentration-dependent manner. At 8 μg/20 μl, this effect was 51% (P<0.001) for capsazepine and 37% (P<0.05) for SB-366791. A TRPA1 antagonist, A-967079, reduced pain reaction by 48% (P<0.05) in the AITC test and by 54% (P<0.001) in the early phase of the formalin test. The test compounds had no influence on the late phase of the formalin test. In paclitaxel-treated mice, they did not attenuate heat hyperalgesia but N-(3-aminopropyl)-2-{[(3-methylphenyl)methyl]oxy}-N-(2-thienylmethyl) benzamide hydrochloride salt (AMTB), a TRPM8 antagonist, reduced cold hyperalgesia and tactile allodynia by 31% (P<0.05) and 51% (P<0.01), respectively. HC-030031, a TRPA1 channel antagonist, attenuated tactile allodynia in the von Frey test (62%; P<0.001). In conclusion, distinct members of TRP channel family are involved in different pain models in mice. Antagonists of TRP channels attenuate nocifensive responses of neurogenic, tonic, and neuropathic pain, but their efficacies strongly depend on the pain model used.