Proglumide enhances the antinociceptive effect of cyclooxygenase inhibitors in diabetic rats in the formalin test

被引：4
|
作者：
Bermudez-Ocana, Deysi Y. [2 ,3 ]
Aguilar-Mariscal, Hidemi [1 ]
Ramon Frias, Teresa [1 ,2 ]
Ble-Castillo, Jorge L. [1 ]
Flores-Murrieta, Francisco J. [4 ,5 ]
Diaz-Zagoya, Juan C. [1 ,6 ]
Granados-Soto, Vinicio [7 ]
Esther Juarez-Rojop, Isela [1 ]
机构：
[1] Univ Juarez Autonoma Tabasco, Div Acad Ciencias Salud, Ctr Invest & Posgrado, Villahermosa 86150, Tabasco, Mexico
[2] Univ Juarez Autonoma Tabasco, Div Acad Multidisciplinaria Comalcalco, Comalcalco, Tabasco, Mexico
[3] Hosp Alta Especialidad Dr Gustavo A Rovirosa Pere, Villahermosa, Tabasco, Mexico
[4] Secretaria Salud Mexico, Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
[5] Inst Politecn Nacl, Escuela Super Med, Secc Estudios Posgrado & Invest, Mexico City, DF, Mexico
[6] Univ Nacl Autonoma Mexico, Fac Med, Dept Bioquim, Mexico City, DF, Mexico
[7] Ctr Invest & Estudios Avanzados, Dept Farmacobiol, Mexico City, DF, Mexico
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY | 2011年 / 664卷 / 1-3期
关键词：
Diabetes; Meloxicam; Ketorolac; Cholecystokinin; Proglumide; MORPHINE-INDUCED ANALGESIA; PRIMARY SENSORY NEURONS; CYCLIC GMP PATHWAY; INDUCED PAIN MODEL; SPINAL-CORD; NEUROPATHIC PAIN; RECEPTOR ANTAGONIST; MECHANICAL HYPERALGESIA; CHOLECYSTOKININ ANTAGONIST; PERIPHERAL PROSTAGLANDINS;
D O I：
10.1016/j.ejphar.2011.04.044
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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. (C) 2011 Elsevier B.V. All rights reserved.
引用
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页码：8 / 13
页数：6
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