Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-<span style="font-variant: small-caps">l</span>-Carnitine on Experimental Model of Inflammatory Pain

• Main Authors: Alessio Ardizzone, Roberta Fusco, Giovanna Casili, Marika Lanza, Daniela Impellizzeri, Emanuela Esposito, Salvatore Cuzzocrea
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: Palmitoylethanolamide (PEA); acetyl-<span style="font-variant: small-caps">l</span>-carnitine (LAC); carrageenan (CAR); edema; inflammatory pain
• Online Access: https://www.mdpi.com/1422-0067/22/4/1967

Palmitoylethanolamide (PEA), a fatty acid amide, has been widely investigated for its analgesic and anti-inflammatory properties. The ultra-micronized formulation of PEA (um-PEA), that has an enhanced rate of dissolution, is extensively used. Acetyl-<span style="font-variant: small-caps;">l</span>-carnitine (LAC), employed for the treatment of neuropathic pain in humans, is able to cause analgesia by up-regulating type-2 metabotropic glutamate (mGlu2) receptors. In the present study, we tested different associations of um-PEA, LAC and non-micronized PEA (non-m-PEA) in a rat model of carrageenan (CAR)-induced paw edema. Intraplantar injection of CAR into the hind paw of animals caused edema, thermal hyperalgesia, accumulation of infiltrating inflammatory cells and augmented myeloperoxidase (MPO) activity. All these parameters were decreased in a significantly manner by oral administration of a compound constituted by a mixture of um-PEA and LAC in relation 1:1 (5 mg/kg), but not with the association of single compounds administered one after the other. These findings showed the superior anti-inflammatory and anti-nociceptive action displayed by oral administration of um-PEA and LAC versus LAC plus, separate but consecutive, um-PEA in the rat paw CAR model of inflammatory pain.