加巴喷丁和普瑞巴林可与萘普生协同作用产生抗痛觉过敏效果。

Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia.

作者信息

Hurley Robert W, Chatterjea Debika, Rose Feng Meihua, Taylor Charles P, Hammond Donna L

机构信息

Department of Anesthesia and Critical Care, and Committee on Neurobiology, University of Chicago, Illinois, USA.

出版信息

Anesthesiology. 2002 Nov;97(5):1263-73. doi: 10.1097/00000542-200211000-00033.

DOI:10.1097/00000542-200211000-00033

PMID:12411814

Abstract

BACKGROUND

Gabapentin and pregabalin are anticonvulsants with antihyperalgesic effects in animal models of neuropathic and inflammatory nociception. This study characterized the manner in which gabapentin or pregabalin interacts with naproxen to suppress thermal hyperalgesia and inflammation in the carrageenan model of peripheral inflammation.

METHODS

Gabapentin, pregabalin, naproxen, or a fixed-dose ratio of gabapentin + naproxen or pregabalin + naproxen was administered orally to rats after the induction of inflammation by intraplantar injection of lambda-carrageenan in one hind paw. Nociceptive thresholds were determined by the radiant heat paw-withdrawal test. Paw edema was measured by plethysmometry. Drug plasma concentrations were determined by a liquid chromatography-mass spectroscopy-mass spectroscopy method.

RESULTS

Gabapentin, pregabalin, and naproxen alone reversed thermal hyperalgesia with ED50 values of 19.2, 6.0, and 0.5 mg/kg, respectively. Mixtures of gabapentin + naproxen in fixed-dose ratios of 50:1, 10:1, or 1:1 interacted synergistically to reverse carrageenan-induced thermal hyperalgesia. However, 1:50 gabapentin + naproxen produced only additive effects. No combination of gabapentin + naproxen decreased paw edema in a manner greater than additive. Plasma concentrations of gabapentin and naproxen were unaltered by the addition of the other drug. The mixture of 10:1 of pregabalin + naproxen interacted synergistically to reverse thermal hyperalgesia on the inflamed hind paw, whereas mixtures of 1:1 or 1:10 produced additive effects.

CONCLUSIONS

These data suggest that gabapentin + naproxen and pregabalin + naproxen can interact synergistically or additively to reverse thermal hyperalgesia associated with peripheral inflammation. Therefore, the use of gabapentin or pregabalin in low-dose combinations with naproxen may afford therapeutic advantages for clinical treatment of persistent inflammatory pain.

摘要

背景

加巴喷丁和普瑞巴林是抗惊厥药，在神经性和炎性伤害感受的动物模型中具有抗痛觉过敏作用。本研究描述了加巴喷丁或普瑞巴林与萘普生相互作用以抑制角叉菜胶诱导的外周炎症模型中的热痛觉过敏和炎症的方式。

方法

在大鼠一侧后爪足底注射λ-角叉菜胶诱导炎症后，口服给予加巴喷丁、普瑞巴林、萘普生，或加巴喷丁+萘普生或普瑞巴林+萘普生的固定剂量比组合。通过辐射热缩爪试验测定伤害性感受阈值。通过体积描记法测量爪部水肿。采用液相色谱-质谱-质谱法测定药物血浆浓度。

结果

单独使用加巴喷丁、普瑞巴林和萘普生均可逆转热痛觉过敏，其半数有效剂量（ED50）值分别为19.2、6.0和0.5mg/kg。加巴喷丁+萘普生以50:1、10:1或1:1的固定剂量比混合时，协同作用逆转角叉菜胶诱导的热痛觉过敏。然而，1:50的加巴喷丁+萘普生仅产生相加作用。加巴喷丁与萘普生的任何组合均未以大于相加的方式减轻爪部水肿。加用另一种药物后，加巴喷丁和萘普生的血浆浓度未发生改变。普瑞巴林+萘普生10:1的混合物协同作用逆转炎症后爪部的热痛觉过敏，而1:1或1:10的混合物产生相加作用。