Drinovac Višnja, Bach-Rojecky Lidija, Babić Ana, Lacković Zdravko
Department of Pharmacology, University of Zagreb Faculty of Pharmacy and Biochemistry, 10000 Zagreb, Croatia.
Laboratory of Molecular Neuropharmacology, Department of Pharmacology and Croatian Brain Research Institute, University of Zagreb Medical School, 10000 Zagreb, Croatia.
Eur J Pharmacol. 2014 Dec 15;745:190-5. doi: 10.1016/j.ejphar.2014.10.038. Epub 2014 Oct 30.
Visceral pain, especially in the abdominal region, represents one of the most common types of pain. Its chronic form is usually very hard to treat by conventional analgesic agents and adjuvants. We investigated the antinociceptive effect of botulinum toxin type A (BTX-A) in male Wistar rats in two models of visceral pain: peritonitis induced by intraperitoneal injection of 1% acetic acid and colitis induced by intracolonic instillation of 0.1% capsaicin. Pain was measured as the number of abdominal writhes. Additionally, referred mechanical sensitivity in the ventral abdominal area was evaluated by von Frey test and the extent of spinal c-Fos expression was immunohistochemically examined. BTX-A significantly reduced the number of abdominal writhes in both models of visceral pain after intrathecal application in a dose of 2 U/kg. In the experimental colitis model, BTX-A (2 U/kg) reduced both referred mechanical allodynia and c-Fos expression in the dorsal horn of the spinal cord (S2/S3 segments). In contrast to intrathecal administration, BTX-A (2 U/kg) administered into the cisterna magna had no effect on pain suggesting that the primary site of its action is a spinal cord.
内脏痛,尤其是腹部区域的疼痛,是最常见的疼痛类型之一。其慢性形式通常很难用传统的镇痛药和辅助药物治疗。我们在两种内脏痛模型中研究了A型肉毒杆菌毒素(BTX-A)对雄性Wistar大鼠的镇痛作用:腹腔注射1%醋酸诱导的腹膜炎和结肠内灌注0.1%辣椒素诱导的结肠炎。疼痛以腹部扭动次数来衡量。此外,通过von Frey试验评估腹侧腹部区域的牵涉性机械敏感性,并通过免疫组织化学检查脊髓c-Fos表达的程度。鞘内注射2 U/kg剂量的BTX-A后,在两种内脏痛模型中均显著减少了腹部扭动次数。在实验性结肠炎模型中,BTX-A(2 U/kg)降低了脊髓背角(S2/S3节段)的牵涉性机械异常性疼痛和c-Fos表达。与鞘内给药相反,向小脑延髓池注射BTX-A(2 U/kg)对疼痛没有影响,这表明其主要作用部位是脊髓。