Effectiveness of a course treatment with palmitoylethanolamide and transplantation of mesenchymal stem cells in experimental peripheral neuropathic pain

Abstract

Aim. To study the effect of repeated intraperitoneal administration of palmitoylethanolamide (PEA, 1 mg/kg) in combination with a single intramuscular injection of adipose-derived mesenchymal stem cells (ADMSCs, 1×10⁶ cells/kg) on nociceptive reactions and morphological changes in tissues of the hind legs of rats with peripheral neuropathic pain (PNP) due to sciatic nerve transection. Methods. The study was conducted on 28 Wistar male rats. The study design included modeling of NP without treatment; NP with a single transplantation of ADMSCs; and NP with a single local transplantation of ADMSCs and a course treatment with PEA. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) were measured weekly for 28 days and on day 60. On day 21 of experiment, the histological structure of soft tissues and neurovascular bundle of the hind paws of NP rats was assessed after transplantation of ADMSCs alone and in combination with the PEA course treatment. Results. A single administration of ADMSCs increased the MWT and TWL in rats with PNP to the baseline values of postoperative day 21, inhibited inflammation of perineural tissues, and improved neovascularization of the vascular bundle in the sciatic axotomy area. A course of PEA intraperitoneal injections in combination with the ADMSCs transplantation increased MWT after the first PEA injection but did not result in recovery of the nociceptive sensitivity to mechanical and thermal stimuli throughout the study, and also abolished the anti-inflammatory effect of ADMSCs. Conclusion. A combination of repeated PEA injections and ADMSCs reduced the antinociceptive effect of stem cells and abolished their anti-inflammatory effect in the area of sciatic nerve resection.