Recent studies have shown that topiramate, a structurally novel anticonvulsant, exerts antinociceptive activity in animal models of neuropathic, acute somatic, and visceral pain. This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma-aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate's antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of systemic and local peripheral topiramate on carrageenan-induced hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline (selective GABAA receptor antagonist), naloxone (nonselective opioid receptor antagonist), and yohimbine (selective 2-adrenergic receptor antagonist) on topiramate-induced antihyperalgesia. Systemic topiramate (40160mg/kg; p.o.) produ...ced a significant dose-dependent reduction in the paw inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of systemic topiramate was significantly decreased by systemic bicuculline (0.51mg/kg; i.p.), naloxone (25mg/kg; i.p.), and yohimbine (13mg/kg; i.p.). Local peripheral topiramate (0.030.34mg/paw; i.pl.) also produced significant dose-dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.050.2mg/paw; i.pl.) but not by local peripheral bicuculline (0.15mg/paw; i.pl.) or naloxone (0.1mg/paw; i.pl.). The results suggest that topiramate produces systemic and local peripheral antihyperalgesia in an inflammatory pain model, which is, at least partially, mediated by central GABAA and opioid receptors and by peripheral and most probably central 2-adrenergic receptors. These findings contribute to better understanding of topiramate's action in pain states involving inflammation.
TY - JOUR
AU - Paranos, Sonja
AU - Tomić, Maja
AU - Micov, Ana
AU - Stepanović-Petrović, Radica
PY - 2013
UR - http://farfar.pharmacy.bg.ac.rs/handle/123456789/1986
AB - Recent studies have shown that topiramate, a structurally novel anticonvulsant, exerts antinociceptive activity in animal models of neuropathic, acute somatic, and visceral pain. This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma-aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate's antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of systemic and local peripheral topiramate on carrageenan-induced hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline (selective GABAA receptor antagonist), naloxone (nonselective opioid receptor antagonist), and yohimbine (selective 2-adrenergic receptor antagonist) on topiramate-induced antihyperalgesia. Systemic topiramate (40160mg/kg; p.o.) produced a significant dose-dependent reduction in the paw inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of systemic topiramate was significantly decreased by systemic bicuculline (0.51mg/kg; i.p.), naloxone (25mg/kg; i.p.), and yohimbine (13mg/kg; i.p.). Local peripheral topiramate (0.030.34mg/paw; i.pl.) also produced significant dose-dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.050.2mg/paw; i.pl.) but not by local peripheral bicuculline (0.15mg/paw; i.pl.) or naloxone (0.1mg/paw; i.pl.). The results suggest that topiramate produces systemic and local peripheral antihyperalgesia in an inflammatory pain model, which is, at least partially, mediated by central GABAA and opioid receptors and by peripheral and most probably central 2-adrenergic receptors. These findings contribute to better understanding of topiramate's action in pain states involving inflammation.
PB - Wiley-Blackwell, Hoboken
T2 - Fundamental & Clinical Pharmacology
T1 - The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia
VL - 27
IS - 3
SP - 319
EP - 328
DO - 10.1111/j.1472-8206.2011.01018.x
ER -
@article{
author = "Paranos, Sonja and Tomić, Maja and Micov, Ana and Stepanović-Petrović, Radica",
year = "2013",
url = "http://farfar.pharmacy.bg.ac.rs/handle/123456789/1986",
abstract = "Recent studies have shown that topiramate, a structurally novel anticonvulsant, exerts antinociceptive activity in animal models of neuropathic, acute somatic, and visceral pain. This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma-aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate's antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of systemic and local peripheral topiramate on carrageenan-induced hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline (selective GABAA receptor antagonist), naloxone (nonselective opioid receptor antagonist), and yohimbine (selective 2-adrenergic receptor antagonist) on topiramate-induced antihyperalgesia. Systemic topiramate (40160mg/kg; p.o.) produced a significant dose-dependent reduction in the paw inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of systemic topiramate was significantly decreased by systemic bicuculline (0.51mg/kg; i.p.), naloxone (25mg/kg; i.p.), and yohimbine (13mg/kg; i.p.). Local peripheral topiramate (0.030.34mg/paw; i.pl.) also produced significant dose-dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.050.2mg/paw; i.pl.) but not by local peripheral bicuculline (0.15mg/paw; i.pl.) or naloxone (0.1mg/paw; i.pl.). The results suggest that topiramate produces systemic and local peripheral antihyperalgesia in an inflammatory pain model, which is, at least partially, mediated by central GABAA and opioid receptors and by peripheral and most probably central 2-adrenergic receptors. These findings contribute to better understanding of topiramate's action in pain states involving inflammation.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Fundamental & Clinical Pharmacology",
title = "The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia",
volume = "27",
number = "3",
pages = "319-328",
doi = "10.1111/j.1472-8206.2011.01018.x"
}
Paranos S, Tomić M, Micov A, Stepanović-Petrović R. The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia. Fundamental & Clinical Pharmacology. 2013;27(3):319-328
Paranos, S., Tomić, M., Micov, A.,& Stepanović-Petrović, R. (2013). The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia.
Fundamental & Clinical PharmacologyWiley-Blackwell, Hoboken., 27(3), 319-328.
https://doi.org/10.1111/j.1472-8206.2011.01018.x
Paranos Sonja, Tomić Maja, Micov Ana, Stepanović-Petrović Radica, "The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia" 27, no. 3 (2013):319-328,
https://doi.org/10.1111/j.1472-8206.2011.01018.x .
