Oliveira Sara Marchesan, Silva Cássia Regina, Wentz Alexandre Pereira, Paim Gisele R, Correa Michele S, Bonacorso Hélio G, Prudente Arthur S, Otuki Michel Fleith, Ferreira Juliano
Laboratório de Neurotoxicidade e Psicofarmacologia, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS 97.105-900, Brazil; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, RS 97.105-900, Brazil.
Laboratório de Neurotoxicidade e Psicofarmacologia, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS 97.105-900, Brazil.
Pharmacol Biochem Behav. 2014 Sep;124:396-404. doi: 10.1016/j.pbb.2014.07.005. Epub 2014 Jul 16.
Pain is the most common complaint in the medical field and the identification of novel compounds that can effectively treat painful states without causing side effects remains a major challenge in biomedical research. The aim of the present study is to investigate the antinociceptive effect of 3-(4-fluorophenyl)-5-trifluoromethyl-1H-1-tosylpyrazole (FTosPz) in models of pathological pain in mice and compare these effects with those produced by Celecoxib. FTosPz (100-500 μmol/kg) or Celecoxib (26-260 μmol/kg) was administrated orally. The administration of either FTosPz or Celecoxib reduced the hyperalgesia but not the edema or leukocyte infiltration that was caused by Complete Freund's Adjuvant (CFA), used as an arthritis model. Oral administration of both FTosPz and Celecoxib also attenuated the postoperative hyperalgesia as well as the hyperalgesia caused by partial sciatic nerve ligation, used as a neuropathic pain model. FTosPz and Celecoxib produced antinociceptive effects without altering the locomotor activity of animals. Furthermore, FTosPz neither altered AST/ALT enzyme activity nor the urea/creatinine levels. Still, the FTosPz did not alter the COX-1 and COX-2 enzyme activities. Thus, FTosPz is an interesting prototype for the development of novel analgesic drugs.
疼痛是医学领域最常见的主诉,鉴定能够有效治疗疼痛状态且无副作用的新型化合物仍是生物医学研究中的一项重大挑战。本研究的目的是在小鼠病理性疼痛模型中研究3-(4-氟苯基)-5-三氟甲基-1H-1-甲苯磺酰基吡唑(FTosPz)的抗伤害感受作用,并将这些作用与塞来昔布产生的作用进行比较。口服给予FTosPz(100 - 500μmol/kg)或塞来昔布(26 - 260μmol/kg)。作为关节炎模型的完全弗氏佐剂(CFA)引起的痛觉过敏,但不是水肿或白细胞浸润,FTosPz或塞来昔布的给药均可减轻。口服FTosPz和塞来昔布也可减轻术后痛觉过敏以及作为神经性疼痛模型的部分坐骨神经结扎引起的痛觉过敏。FTosPz和塞来昔布产生抗伤害感受作用而不改变动物的运动活性。此外,FTosPz既不改变AST/ALT酶活性,也不改变尿素/肌酐水平。而且,FTosPz不改变COX-1和COX-2酶活性。因此,FTosPz是开发新型镇痛药的一个有前景的原型。