Ciproxifan在小鼠痛觉传导调节机制中的作用

摘要

AIM:To investigate the effects of ciproxifan (CPF) in modulation of pain transmission in mice and its mechanism. METHODES:The antinociceptive effect of CPF was observed at the absence and presence of α-fluoromethylhistidine (α-FMH), a specific inhibitor of histidine decarboxylase (HDC), in three hyperalgesic models of mice (hot plate test, writhing test and formalin test). Furthermore, the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in brain, spinal and serum were assessed after formalin stimulation. RESULTS: Intraperitoneal (ip) administration of CPF 1, 3 mg·kg-1 could produce antinociception in hot plate test. And CPF 1 mg·kg-1 (ip) could decrease the numbers of writhing with the highest inhibitory rate of 49.85 % in writhing test. In formalin test, the subcutaneous formalin evoked biphasic (phaseⅠand phaseⅡ) licking behavior of the injected paw. The licking times of both phases were significantly decreased in CPF 0.3, 1, 3 mg·kg-1 groups. All of the antinociceptive effects of CPF in three hyperalgesic models could be reversed by α-FMH (50 mg·kg-1, ip). Administration of CPF could decrease the elevated levels of NO and PGE2 induced by formalin in spinal and brain rather than in serum. CONCLUSION:CPF possesses antinociception in three hyperalgesic models of mice and is effective in both inflammatory and non-inflammatory pain induced by formalin. The antinociceptive effect of CPF might be related to the release of histamine, meanwhile, NO and PGE2 in spinal and brain might participate in the process of CPF antinociception.%目的:研究组胺H3受体拮抗剂ciproxifan(CPF)在小鼠痛觉传导调节过程中的作用及其机制.方法:用3种不同的小鼠痛觉模型(热板法、扭体法和福尔马林实验)观察CPF的镇痛作用.同时用特异性组胺脱羧酶(HDC)抑制药α-氟甲基组胺酸(α-FMH),观察组胺在CPF发挥镇痛效应过程中所起的作用.在福尔马林致痛模型中,还测定了小鼠脑、脊髓和血清中一氧化氮(NO)和前列腺素E2(PGE2)的含量.结果:热板实验中,CPF 1 mg%.皮下注射福尔马林能引起2个时相(Ⅰ相、Ⅱ相)的痛反应.这种由福尔马林引起的2个时相的痛反应均可明显被CPF 0.3, 1, 3 mg*kg-1抑制. 在3种致痛模型中,CPF的镇痛效应均可被α-FMH 50 mg*kg-1逆转.使用福尔马林后,小鼠脑和脊髓中NO和PGE2水平升高,而CPF能明显抑制这种升高作用,该抑制作用不被α-FMH所拮抗.但CPF对血清中NO和PGE2的浓度没有影响.结论:组胺H3受体拮抗药CPF对多种性质刺激引起的疼痛均有镇痛作用,对福尔马林引起的炎性疼痛和非炎性疼痛都有效.CPF的这种镇痛作用可能与其促进组胺释放有关;同时脑和脊髓中的NO和PGE2可能参与了CPF的镇痛作用.