Safinamide alleviates hyperalgesia via inhibiting hyperexcitability of DRG neurons in a mouse model of Parkinson's disease

Li-Ge Zhang; Jing Cheng; Meng-Qi An; Cheng-Jie Li; Li-Guo Dong; Jian-Min Wang; Chun-Feng Liu; Fen Wang; Cheng-Jie Mao

doi:10.1016/j.bbr.2023.114787

Safinamide alleviates hyperalgesia via inhibiting hyperexcitability of DRG neurons in a mouse model of Parkinson's disease

Behav Brain Res. 2024 Feb 29:459:114787. doi: 10.1016/j.bbr.2023.114787. Epub 2023 Dec 1.

Authors

Li-Ge Zhang¹, Jing Cheng¹, Meng-Qi An², Cheng-Jie Li³, Li-Guo Dong³, Jian-Min Wang³, Chun-Feng Liu¹, Fen Wang⁴, Cheng-Jie Mao⁵

Affiliations

¹ Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
² Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
³ Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
⁴ Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China. Electronic address: wangfen_1982@126.com.
⁵ Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: drchengjiemao@163.com.

PMID: 38042302
DOI: 10.1016/j.bbr.2023.114787

Abstract

Pain is a widespread non-motor symptom that presents significant treatment challenges in patients with Parkinson's disease (PD). Safinamide, a new drug recently introduced for PD treatment, has demonstrated analgesic effects on pain in PD patients, though the underlying mechanisms remain unclear. To investigate the analgesic and anti-PD effect of safinamide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was used, and rasagiline as positive control on motor symptoms. Notably, only safinamide alleviated hyperalgesia in MPTP mice. Whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons revealed hyperexcitability in MPTP mice, which safinamide counteracted in a concentration-dependent manner. The voltage clamp further demonstrated that sodium current in DRG neurons of MPTP mice was enhanced and safinamide reduced sodium current density. RT-qPCR identified upregulated Nav1.7 and Nav1.8 transcripts (Scn9a and Scn10a) in DRG neurons of MPTP mice. Our results suggest that safinamide could relieve hyperalgesia by inhibiting DRG neuron hyperexcitability in MPTP mice.

Keywords: Dorsal root ganglion; Hyperalgesia; Membrane excitability; Parkinson's disease; Safinamide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analgesics / pharmacology
Animals
Ganglia, Spinal
Humans
Hyperalgesia* / drug therapy
Mice
Neurons / physiology
Pain
Parkinson Disease* / complications
Parkinson Disease* / drug therapy
Sodium / pharmacology

Substances

safinamide
Analgesics
Sodium