División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Comalcalco, Mexico.
Eur J Pharmacol. 2011 Aug 16;664(1-3):8-13. doi: 10.1016/j.ejphar.2011.04.044. Epub 2011 May 1.
The purpose of this study was to assess the effect of the non-selective cholecystokinin receptor antagonist proglumide on the antinociceptive activity of ketorolac and meloxicam in non-diabetic and diabetic rats. Streptozotocin (60 mg/kg) injection caused hyperglycemia which was maintained for 2 weeks. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Local peripheral ipsilateral, but not contralateral, administration of ketorolac and meloxicam produced antinociception in non-diabetic and diabetic rats. However, the antinociceptive effect of both drugs was significantly reduced in diabetic animals. Proglumide was ineffective by itself and it did not affect the antinociception induced by the cyclooxygenase inhibitors in non-diabetic rats. Contrariwise, proglumide reduced formalin-induced nociception and it increased ketorolac- or meloxicam-induced antinociception in diabetic rats. These results suggest that peripheral cholecystokinin plays an important role in diabetes-induced sensitization as well as in the reduction of the antinociceptive effects of ketorolac and meloxicam in diabetic rats. The combination of cholecystokinin receptor antagonists and ketorolac or meloxicam may be a useful strategy to reduce nociception in diabetic patients.
本研究旨在评估非选择性胆囊收缩素受体拮抗剂丙谷胺对酮咯酸和美洛昔康在非糖尿病和糖尿病大鼠中的抗伤害作用的影响。链脲佐菌素（60mg/kg）注射导致高血糖，持续 2 周。与非糖尿病大鼠相比，糖尿病大鼠的福尔马林诱发的退缩增加。局部外周同侧，而非对侧，给予酮咯酸和美洛昔康在非糖尿病和糖尿病大鼠中产生镇痛作用。然而，两种药物的镇痛作用在糖尿病动物中显著降低。丙谷胺本身无效，它不影响环氧化酶抑制剂在非糖尿病大鼠中引起的镇痛作用。相反，丙谷胺降低了福尔马林引起的疼痛，并增加了糖尿病大鼠中酮咯酸或美洛昔康引起的镇痛作用。这些结果表明，外周胆囊收缩素在糖尿病引起的敏化以及在糖尿病大鼠中酮咯酸和美洛昔康的镇痛作用降低中起重要作用。胆囊收缩素受体拮抗剂与酮咯酸或美洛昔康的联合应用可能是减少糖尿病患者疼痛的有效策略。
