TY - JOUR
T1 - Proglumide enhances the antinociceptive effect of cyclooxygenase inhibitors in diabetic rats in the formalin test
AU - Bermúdez-Ocaña, Deysi Y.
AU - Aguilar-Mariscal, Hidemi
AU - Frías, Teresa Ramón
AU - Blé-Castillo, Jorge L.
AU - Flores-Murrieta, Francisco J.
AU - Díaz-Zagoya, Juan C.
AU - Granados-Soto, Vinicio
AU - Juárez-Rojop, Isela Esther
N1 - Funding Information:
This work is part of the B.Sc. dissertation of Robert G. De la Cruz-Arellano. This study was supported by PROMEP grant 103.5/07/2417 .
PY - 2011/8/16
Y1 - 2011/8/16
N2 - 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.
AB - 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.
KW - Cholecystokinin
KW - Diabetes
KW - Ketorolac
KW - Meloxicam
KW - Proglumide
UR - http://www.scopus.com/inward/record.url?scp=79957910122&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2011.04.044
DO - 10.1016/j.ejphar.2011.04.044
M3 - Artículo
SN - 0014-2999
VL - 664
SP - 8
EP - 13
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -