The antihyperalgesic effect of venlafaxine in diabetic rats does not involve the opioid system.
Venlafaxine (VFX) is a structurally novel antidepressant that inhibits reuptake of serotonin and norepinephrine but, unlike tricyclic antidepressants, has few side effects. The present work studies the antihyperalgesic effect of repeated administrations of VFX (five successive injections of 2.5, 5 or 10 mg/kg, s.c., every half-life) in diabetic rats with the paw pressure test and the effect of the opioid receptor antagonist naloxone (1 mg/kg, i.v.) because an opioidergic mechanism is usually considered to be involved in the analgesic effect of antidepressants. VFX induced a significant dose-dependent increase in vocalization thresholds. This effect was not reversed by naloxone. Thus, we demonstrate a clear antinociceptive effect of VFX which, unlike that of most mixed tricyclic antidepressants, does not involve the endogenous opioid system.
E 9904 INSERM/UdA, Laboratoire de Pharmacologie Médicale, Faculté de Médecine, 63001 Cedex 1, Clermont-Ferrand, France.
Fabien
F
Marchand
Abdelkrim
A
Alloui
Eric
E
Chapuy
Alejandro
A
Hernandez
Teresa
T
Pelissier
Denis
D
Ardid
Alain
A
Eschalier
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003511:Cyclohexanols / Q000494:pharmacology*; D048909:Diabetes Complications; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069470:Venlafaxine Hydrochloride; D014828:Vocalization, Animal / Q000187:drug effects
D000700:Analgesics; D003511:Cyclohexanols; D009292:Narcotic Antagonists; D009270:Naloxone; D000069470:Venlafaxine Hydrochloride