Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, PO Box 146, 11221 Belgrade, Serbia.
Fundam Clin Pharmacol. 2013 Jun;27(3):319-28. doi: 10.1111/j.1472-8206.2011.01018.x. Epub 2011 Dec 5.
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 α2-adrenergic receptor antagonist) on topiramate-induced antihyperalgesia. Systemic topiramate (40-160 mg/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 (0.5-1 mg/kg; i.p.), naloxone (2-5 mg/kg; i.p.), and yohimbine (1-3 mg/kg; i.p.). Local peripheral topiramate (0.03-0.34 mg/paw; i.pl.) also produced significant dose-dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.05-0.2 mg/paw; i.pl.) but not by local peripheral bicuculline (0.15 mg/paw; i.pl.) or naloxone (0.1 mg/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 α2-adrenergic receptors. These findings contribute to better understanding of topiramate's action in pain states involving inflammation.
最近的研究表明，结构新颖的抗惊厥药托吡酯在神经性、急性躯体性和内脏性疼痛的动物模型中具有镇痛作用。本研究旨在探讨：（i）全身性和局部外周给予托吡酯对大鼠炎性疼痛模型的影响；（ii）γ-氨基丁酸（GABA）、阿片类和肾上腺素能受体在托吡酯抗痛觉过敏中的潜在作用和（ii）。大鼠接受足底注射（i.pl.）致炎化合物卡拉胶。使用足底压力测试来确定：（i）全身性和局部外周托吡酯对卡拉胶诱导的痛觉过敏的影响；（ii）全身性和局部外周给予荷包牡丹碱（选择性 GABAA 受体拮抗剂）、纳洛酮（非选择性阿片受体拮抗剂）和育亨宾（选择性α2-肾上腺素能受体拮抗剂）对托吡酯诱导的抗痛觉过敏的影响。全身性托吡酯（40-160 mg/kg；p.o.）可显著降低卡拉胶诱导的足底炎症性痛觉过敏。全身性托吡酯的抗痛觉过敏作用明显被全身性荷包牡丹碱（0.5-1 mg/kg；i.p.）、纳洛酮（2-5 mg/kg；i.p.）和育亨宾（1-3 mg/kg；i.p.）减弱。局部外周托吡酯（0.03-0.34 mg/爪；i.pl.）也产生了显著的剂量依赖性抗痛觉过敏作用，该作用明显被局部外周育亨宾（0.05-0.2 mg/爪；i.pl.）但不被局部外周荷包牡丹碱（0.15 mg/爪；i.pl.）或纳洛酮（0.1 mg/爪；i.pl.）抑制。结果表明，托吡酯在炎症性疼痛模型中产生全身性和局部外周抗痛觉过敏作用，这至少部分是由中枢 GABAA 和阿片受体以及外周和可能是中枢α2-肾上腺素能受体介导的。这些发现有助于更好地理解托吡酯在涉及炎症的疼痛状态中的作用。
