The local antinociceptive effects of paracetamol in neuropathic pain are mediated by cannabinoid receptors.
Paracetamol analgesic mechanism of action is still poorly defined but mainly involves central inhibition of cyclooxygenases. Here we tested the peripheral antinociceptive effects of paracetamol (intraplantar injections) in a rat model of neuropathic pain. Paracetamol dose-dependently decreased mechanical allodynia and lowered nociceptive scores associated with hyperalgesia testing. These effects were inhibited by the administration of cannabinoid CB(1) (AM251) and CB(2) (AM630) receptor antagonists. The participation of the peripheral cannabinoid system in paracetamol analgesia is suggested.
Dani
Mélina
M
Department of Pharmacology, Faculty of Medicine, Université de Montréal - CHUM, 3840 rue St-Urbain, Montréal, H2W 1T8, Québec, Canada.
Guindon
Josée
J
Lambert
Chantal
C
Beaulieu
Pierre
P
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000294:innervation; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries
D018712:Analgesics, Non-Narcotic; D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D000082:Acetaminophen; C103505:AM 251; C094023:iodopravadoline; C107594:N-(4-hydroxyphenyl)arachidonylamide