Antinociceptive effects of palmitoylethanolamide and stearoylethanolamide upon PPARγ receptor blockade in rats with peripheral neuropathy

Objectives. To investigate the role of PPARγ receptors in realization of the antinociceptive effects of PEA and SEA in rats with peripheral neuropathy. Material and methods. Interaction of palmitoylethanolamide and stearoylethanolamide with the PPARγ receptor was studied using the molecular computer modeling to evaluate the binding affinity and stability of these complexes. The antinociceptive effects of acylethanolamides on PPARγ receptor blockade in rats with peripheral mononeuropathy were studied. Results. Computer molecular modeling between acylethanolamides and the PPARγ receptor has shown the formation of stable complexes characterized by the formation of intermolecular hydrogen bonds and a network of hydrophobic interactions. The obtained results substantiate the feasibility of an experimental assessment of the involvement of PPARγ receptors in the antinociceptive effects of acylethanolamides. Administration of palmitoylethanolamide and stearoylethanolamide to rats with peripheral mononeuropathy with PPARγ receptor blockade reduced the threshold of nociceptive reactions and the latent period of nociceptive reactions compared with the values of the group administered with acylethanolamides without blockade. Single administration of palmitoylethanolamide with PPARγ receptor blockade reduced the area and intensity of the ipsilateral limb imprint in animals with neuropathy compared with administration of the test substance without PPARγ receptor blockade. Conclusions. The realization of the antinociceptive effects of palmitoylethanolamide and stearoylethanamide in response to thermal and mechanical stimuli is mediated by PPARγ receptors.