Faculty Collaboration Database

Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia. Anesthesiology 2002 Nov;97(5):1263-73

Date

11/02/2002

Pubmed ID

12411814

DOI

10.1097/00000542-200211000-00033

Scopus ID

2-s2.0-0036840787 (requires institutional sign-in at Scopus site)   148 Citations

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.

Author List

Hurley RW, Chatterjea D, Rose Feng M, Taylor CP, Hammond DL

Author

Robert W. Hurley MD, PhD Adjunct Professor of Anesthesiology and CTSI in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetates
Amines
Analgesics
Animals
Anti-Inflammatory Agents, Non-Steroidal
Calcium
Calcium Channels
Cyclohexanecarboxylic Acids
Drug Synergism
Hyperalgesia
Male
Naproxen
Pregabalin
Rats
Rats, Sprague-Dawley
gamma-Aminobutyric Acid