Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

Abstract

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.

• Authors: Maja A Tomić, Sonja M Vucković, Radica M Stepanović-Petrović, Nenad D Ugresić, Milica S Prostran, Bogdan Bosković
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 110 Issue 4 Pg. 1198-205 (Apr 01 2010) ISSN: 1526-7598 [Electronic] United States
• PMID: 20142344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Non-Narcotic
• Anticonvulsants
• Carbamazepine
• Acetaminophen
• Carrageenan
• Acetic Acid
• Oxcarbazepine

Topics

• Acetaminophen (pharmacology)
• Acetic Acid
• Algorithms
• Analgesics, Non-Narcotic (pharmacology)
• Animals
• Anticonvulsants (pharmacology)
• Carbamazepine (analogs & derivatives, pharmacology)
• Carrageenan
• Dose-Response Relationship, Drug
• Drug Synergism
• Hyperalgesia (chemically induced, prevention & control)
• Male
• Mice
• Oxcarbazepine
• Pain (drug therapy)
• Rats
• Rats, Wistar