Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.
BACKGROUND
Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components.


METHODS
The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis.


RESULTS
Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50).


CONCLUSIONS
The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.
Faculty of Pharmacy, Department of Pharmacology, University of Belgrade, Vojvode Stepe 450, Belgrade, Serbia. majat@pharmacy.bg.ac.rs
Maja A
MA
Tomić
Sonja M
SM
Vucković
Radica M
RM
Stepanović-Petrović
Nenad D
ND
Ugresić
Milica S
MS
Prostran
Bogdan
B
Bosković
D000082:Acetaminophen / Q000494:pharmacology*; D019342:Acetic Acid; D000465:Algorithms; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D000078330:Oxcarbazepine; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000927:Anticonvulsants; D002220:Carbamazepine; D000082:Acetaminophen; D002351:Carrageenan; D019342:Acetic Acid; D000078330:Oxcarbazepine