Participation of opioid and monoaminergic mechanisms on the antinociceptive effect induced by tricyclic antidepressants in two behavioural pain tests in mice.
1. Various clinical and experimental reports indicate that tricyclic antidepressant drugs are specially useful in the treatment of chronic and acute pain conditions. The present work was aimed to study the mechanisms implicated in the antinociceptive response induced by these antidepressants on different experimental models of pain in mice, and particularly the role played by noradrenergic, serotonergic and opioidergic influences. 2. Electrical stimulation of the tail and formalin tests were used to evaluate pain perception in mice acutely treated with different antidepressants (imipramine, desipramine, amitriptyline, nortriptyline, clomipramine and desmethylclomipramine). Antinociceptive responses were more potent in formalin test than in tail electrical stimulation test. 3. These antinociceptive effects were inhibited by naloxone (2 mg/Kg, i.p.), alpha-methyl-p-tyrosine (200 mg/Kg) and p-chlorophenylalanine (600 mg/Kg). Naloxone elicited the same effectivity to inhibit antinociceptive responses induced by tricyclic antidepressants in both tail electrical stimulation and formalin tests. alpha-methyl-p-tyrosine and p-chlorophenylalanine were more effective on antinociceptive responses induced on formalin than in tail electrical stimulation test. 4. These results suggest that tricyclic antidepressants produce antinociception partly via the participation of the endogenous opioid system and partly by further activating noradrenergic and serotonergic pathways. Moreover, the analgesic responses and the mechanisms implicated were dependent of the analgesimeter test used.
Valverde
O
O
Departamento de Neurociencias, Facultad de Medicina, Cádiz, Spain.
Micó
J A
JA
Maldonado
R
R
Mellado
M
M
Gibert-Rahola
J
J
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000502:physiology*; D004558:Electric Stimulation; D004723:Endorphins / Q000502:physiology*; D010134:Fenclonine / Q000494:pharmacology; D005557:Formaldehyde; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D013623:Tail / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D000700:Analgesics; D000929:Antidepressive Agents, Tricyclic; D015306:Biogenic Monoamines; D004723:Endorphins; D008781:Methyltyrosines; D005557:Formaldehyde; D009270:Naloxone; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D010134:Fenclonine