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Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents

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Authors
Tomić, Maja
Vučković, Sonja M.
Stepanović-Petrović, Radica
Ugrešić, Nenad
Prostran, Milica
Bošković, Bogdan
Article (Published version)
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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. (Anesth Analg 2010;110:1198-1205)

Source:
Anesthesia and Analgesia, 2010, 110, 4, 1198-1205
Publisher:
  • Lippincott Williams & Wilkins, Philadelphia
Funding / projects:
  • Ispitivanje mehanizma dejstva, interakcija i toksičnih efekata analgetika kao i vazoaktivnih supstanci (RS-145030)

DOI: 10.1213/ANE.0b013e3181cbd8da

ISSN: 0003-2999

PubMed: 20142344

WoS: 000276109200035

Scopus: 2-s2.0-77950967035
[ Google Scholar ]
19
16
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1375
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Tomić, Maja
AU  - Vučković, Sonja M.
AU  - Stepanović-Petrović, Radica
AU  - Ugrešić, Nenad
AU  - Prostran, Milica
AU  - Bošković, Bogdan
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1375
AB  - 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. (Anesth Analg 2010;110:1198-1205)
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents
VL  - 110
IS  - 4
SP  - 1198
EP  - 1205
DO  - 10.1213/ANE.0b013e3181cbd8da
ER  - 
@article{
author = "Tomić, Maja and Vučković, Sonja M. and Stepanović-Petrović, Radica and Ugrešić, Nenad and Prostran, Milica and Bošković, Bogdan",
year = "2010",
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. (Anesth Analg 2010;110:1198-1205)",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
title = "Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents",
volume = "110",
number = "4",
pages = "1198-1205",
doi = "10.1213/ANE.0b013e3181cbd8da"
}
Tomić, M., Vučković, S. M., Stepanović-Petrović, R., Ugrešić, N., Prostran, M.,& Bošković, B.. (2010). Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 110(4), 1198-1205.
https://doi.org/10.1213/ANE.0b013e3181cbd8da
Tomić M, Vučković SM, Stepanović-Petrović R, Ugrešić N, Prostran M, Bošković B. Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents. in Anesthesia and Analgesia. 2010;110(4):1198-1205.
doi:10.1213/ANE.0b013e3181cbd8da .
Tomić, Maja, Vučković, Sonja M., Stepanović-Petrović, Radica, Ugrešić, Nenad, Prostran, Milica, Bošković, Bogdan, "Synergistic Interactions Between Paracetamol and Oxcarbazepine in Somatic and Visceral Pain Models in Rodents" in Anesthesia and Analgesia, 110, no. 4 (2010):1198-1205,
https://doi.org/10.1213/ANE.0b013e3181cbd8da . .

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