CAJ | 학술논문

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.
목적:연구조알H3수체길항제ciproxifan(CPF)재소서통각전도조절과정중적작용급기궤제.방법:용3충불동적소서통각모형(열판법、뉴체법화복이마림실험)관찰CPF적진통작용.동시용특이성조알탈최매(HDC)억제약α-불갑기조알산(α-FMH),관찰조알재CPF발휘진통효응과정중소기적작용.재복이마림치통모형중,환측정료소서뇌、척수화혈청중일양화담(NO)화전렬선소E2(PGE2)적함량.결과:열판실험중,CPF 1 mg%.피하주사복이마림능인기2개시상(Ⅰ상、Ⅱ상)적통반응.저충유복이마림인기적2개시상적통반응균가명현피CPF 0.3, 1, 3 mg*kg-1억제. 재3충치통모형중,CPF적진통효응균가피α-FMH 50 mg*kg-1역전.사용복이마림후,소서뇌화척수중NO화PGE2수평승고,이CPF능명현억제저충승고작용,해억제작용불피α-FMH소길항.단CPF대혈청중NO화PGE2적농도몰유영향.결론:조알H3수체길항약CPF대다충성질자격인기적동통균유진통작용,대복이마림인기적염성동통화비염성동통도유효.CPF적저충진통작용가능여기촉진조알석방유관;동시뇌화척수중적NO화PGE2가능삼여료CPF적진통작용.
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.