The role of fatty acid amides in the change of nociceptive sensitivity and gait patterns in healthy rats and in rats with peripheral neuropathy under pharmacological blockade of GPR18 receptors

Abstract

Objectives. To study the effect of fatty acid amides on nociceptive sensitivity and gait patterns during pharmacological blockade of GPR18 receptors in healthy animals and in rats with peripheral neuropathy. Material and methods. The studies were carried out on white male Wister rats (n=86), divided into 11 groups. The effects of fatty acid amides with ethanolamine and glycine upon blockade of GPR18 receptors after the administration of a PSB-CB5 antagonist on gait parameters (footprint area and intensity, as well as hind limb transfer rate), nociceptive reactions in normal rats and in animals with experimental peripheral neuropathy were studied. Results. Single intraperitoneal injections of the G-protein-coupled membrane receptors antagonist GPR18 at a dose of 1 mg/kg to intact rats did not cause any significant changes in Randall – Sellitto test, Hot-plate test and gait patterns. Injections of one of the fatty acid amides (palmitoylethanolamide, stearoylethanolamide, palmitoylglycinamide) at a dose of 1.5 mg/kg to rats with experimental peripheral neuropathy caused a significant decrease in the nociceptive response to mechanical and thermal stimuli, thereby providing an analgesic effect, which was also confirmed by gait analysis. Against the background of GPR18 receptors blockade in rats with neuropathy, palmitoylglycinamide had a pronounced analgesic effect, which is reflected in significant changes in the values of nociceptive sensitivity, as well as the gait parameters studied. However, after the administration of palmitoylethanolamide to animals with GPR18 receptors blocked, reliable results were obtained only when test Hot-plate and fingerprint area were registered, whereas after the introduction of stearoylethanolamide no statistically significant data were obtained. Conclusions. It has been shown that the pronounced analgesic effect after the administration of palmitoylethanolamide and stearoylethanolamide is mediated through the interaction with orphan receptors. At the same time, the antinociceptive effect of palmitoylglycinamide probably occurs through the activation of other, non-orphan, receptors.

Keywords

• palmitoylethanolamide
• stearoylethanolamide
• palmitoylglycinamide
• gait patterns
• nociception
• neuropathy
• analgesic effect
• fatty acid amides
• orphan receptors