The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia
Само за регистроване кориснике
2013
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
2-adrenoceptors / GABAA receptors / inflammatory hyperalgesia / opioid receptors / topiramateИзвор:
Fundamental & Clinical Pharmacology, 2013, 27, 3, 319-328Издавач:
- Wiley-Blackwell, Hoboken
Финансирање / пројекти:
- Испитивање механизма дејства, интеракција и токсичних ефеката адјувантних аналгетика (RS-MESTD-Basic Research (BR or ON)-175045)
DOI: 10.1111/j.1472-8206.2011.01018.x
ISSN: 0767-3981
PubMed: 22136176
WoS: 000318933000010
Scopus: 2-s2.0-84877816815
Институција/група
PharmacyTY - JOUR AU - Paranos, Sonja AU - Tomić, Maja AU - Micov, Ana AU - Stepanović-Petrović, Radica PY - 2013 UR - https://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", 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.. (2013). The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia. in Fundamental & Clinical Pharmacology Wiley-Blackwell, Hoboken., 27(3), 319-328. https://doi.org/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. in Fundamental & Clinical Pharmacology. 2013;27(3):319-328. doi: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" in Fundamental & Clinical Pharmacology, 27, no. 3 (2013):319-328, https://doi.org/10.1111/j.1472-8206.2011.01018.x . .