Safinamide attenuates systemic inflammatory hyperalgesia associated with reduced neuroimmune signaling and NaV1.7 expression

Systemic inflammatory states are associated with neuroimmune responses and peripheral sensitization involving dysregulation of ion channels and inflammatory mediators. Safinamide, a multi-target drug approved for Parkinson’s disease, exhibits sodium channel–blocking and anti-inflammatory properties, suggesting potential relevance in inflammatory pain. This study investigated the analgesic and neuroimmune effects of safinamide in a lipopolysaccharide (LPS)-induced inflammatory hyperalgesia model in rats.

Thirty-two male Wistar rats were divided into control, LPS, safinamide-treated, and indomethacin-treated groups. Thermal nociception was assessed using Tail-Flick and Hot Plate tests, while motor coordination and exploratory behavior were evaluated using the Rotarod and Open Field tests, respectively. NaV1.7 mRNA expression was evaluated by qRT-PCR, while TLR4, TNF-α, and IL-1β levels were quantified by ELISA and NF-κB p65 protein levels by Western blot in dorsal root ganglion (DRG) tissues.

LPS administration induced significant thermal hyperalgesia and increased NaV1.7, TLR4, NF-κB p65, TNF-α, and IL-1β levels in DRG tissue. Safinamide significantly attenuated thermal hyperalgesia and reduced NaV1.7 expression and inflammatory markers, with effects comparable to or greater than indomethacin, without impairing motor coordination. These findings suggest that safinamide attenuates inflammatory hyperalgesia in association with reduced inflammatory marker expression and NaV1.7 expression, supporting further investigation of its potential role in inflammatory pain.

The authors would like to acknowledge the Student Research Committee of Alborz University of Medical Sciences for their support and assistance in conducting this study. This study was supported by Alborz University of Medical Sciences under grant number [0-0-94-7061]. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alborz University of Medical Sciences, Valiasr St, Azimieh, Karaj, Iran Pedram Gilsamaei, Sevda Shayesteh & Marziyeh Amiri-Andebili Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran The authors declare no competing interests.

The present study was conducted in accordance with the ethical guidelines for the care and use of laboratory animals and was approved by the Ethics Committee of Alborz University of Medical Sciences (Ethics Code: IR.ABZUMS.AEC.1403.004). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

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