Antinociceptive Interactions Between Meloxicam and Gabapentin in Neuropathic Pain Depend on the Ratio used in Combination in Rats

Drug Dev Res. 2016 May;77(3):134-42. doi: 10.1002/ddr.21300. Epub 2016 Apr 4.

Abstract

Preclinical Research Neuropathic pain is particularly difficult to treat because of its diverse etiologies and underlying pathophysiological mechanisms. Drug combinations have been proposed to effectively treat some neuropathies. In the present study the interaction of five combinations of meloxicam and gabapentin, were studied to assess the possible synergistic antinociceptive response in neuropathic pain using the von Frey and acetone tests in rat models. Coadministration of meloxicam and gabapentin increased the antihyperalgesic or antiallodynic effects as compared with the compounds administered alone. The area under the curve (AUC) of the antihyperalgesic effects produced by the combination of the two drugs was generally similar to the theoretical sum of effects produced by each drug alone. However, the AUC of the antiallodynic effect produced by one combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the theoretical sum of the effects produced by each drug alone. The type of final interaction on the drug combinations can be additive or cause potentiation of antinociceptive effects and depends on the proportion of each compound used in dosing. Drug Dev Res 77 : 134-142, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: additive effect; gabapentin; interaction; meloxicam; neuropathic pain.

MeSH terms

  • Amines / administration & dosage*
  • Amines / therapeutic use
  • Analgesics / administration & dosage*
  • Analgesics / therapeutic use
  • Animals
  • Area Under Curve
  • Cyclohexanecarboxylic Acids / administration & dosage*
  • Cyclohexanecarboxylic Acids / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Gabapentin
  • Male
  • Meloxicam
  • Neuralgia / drug therapy*
  • Rats
  • Thiazines / administration & dosage*
  • Thiazines / therapeutic use
  • Thiazoles / administration & dosage*
  • Thiazoles / therapeutic use
  • Treatment Outcome
  • gamma-Aminobutyric Acid / administration & dosage*
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Amines
  • Analgesics
  • Cyclohexanecarboxylic Acids
  • Thiazines
  • Thiazoles
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Meloxicam