Peripheral participation of cholecystokinin in the morphine-induced peripheral antinociceptive effect in non-diabetic and diabetic rats.
The effects of cholecystokinin (CCK-8) and the CCK receptor antagonist proglumide, on antinociception induced by local peripheral (subcutaneous) injected morphine in non-diabetic (ND) and streptozotocin-induced diabetic (D) rats, were examined by means of the formalin test. Morphine induced dose-dependent antinociception both in ND and D rats. However, in D rats, antinociceptive morphine potency was about twofold less than in ND rats. Pre-treatment with CCK-8 abolished the antinociceptive effect of morphine in a dose-dependent manner in both groups of rats. Additionally, proglumide enhanced the antinociceptive effect induced by all doses of morphine tested. Both CCK-8 and proglumide had no effect on flinching behaviour when given alone to ND rats. Unlike ND rats, in D rats proglumide produced dose-dependent antinociception and CCK-8 enhanced formalin-evoked flinches, as observed during the second phase of the test. In conclusion, our data show a decrease in peripheral antinociceptive potency of morphine when diabetes was present. Additionally, peripheral CCK plays an antagonic role to the peripheral antinociceptive effect of morphine, additional to the well known CCK/morphine interaction at spinal and supraspinal level.
Torres-López
Jorge E
JE
Laboratorio Mecanismos del Dolor, Centro de Investigación y Posgrado, División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco, Mexico. jorge.torres@dacs.ujat.mx
Juárez-Rojop
Isela E
IE
Granados-Soto
Vinicio
V
Diaz-Zagoya
Juan C
JC
Flores-Murrieta
Francisco J
FJ
Ortíz-López
José U S
JU
Cruz-Vera
Jorge
J
D000818:Animals; D019540:Area Under Curve; D002766:Cholecystokinin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005557:Formaldehyde / Q000009:adverse effects; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009294:Narcotics / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage; D011377:Proglumide / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D009294:Narcotics; D010446:Peptide Fragments; C410885:cholecystokinin 8; D005557:Formaldehyde; D009020:Morphine; D002766:Cholecystokinin; D011377:Proglumide