期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ijms23179564
关键词
neuropathic pain; tolperisone; pregabalin; CSF glutamate content; synaptosome; neuronal glutamate release
资金
- National Research, Development, and Innovation Fund of Hungary, Hungary [2018-1.3.1-VKE-2018-00030]
Tolperisone, a centrally acting muscle relaxant, shows promising effects in alleviating neuropathic pain, restoring paw pressure threshold and glutamate levels in cerebrospinal fluid. Its mechanism of action primarily involves the blockade of ion channels.
Current treatment approaches to manage neuropathic pain have a slow onset and their use is largely hampered by side-effects, thus there is a significant need for finding new medications. Tolperisone, a centrally acting muscle relaxant with a favorable side effect profile, has been reported to affect ion channels, which are targets for current first-line medications in neuropathic pain. Our aim was to explore its antinociceptive potency in rats developing neuropathic pain evoked by partial sciatic nerve ligation and the mechanisms involved. Acute oral tolperisone restores both the decreased paw pressure threshold and the elevated glutamate level in cerebrospinal fluid in neuropathic rats. These effects were comparable to those of pregabalin, a first-line medication in neuropathy. Tolperisone also inhibits release of glutamate from rat brain synaptosomes primarily by blockade of voltage-dependent sodium channels, although inhibition of calcium channels may also be involved at higher concentrations. However, pregabalin fails to affect glutamate release under our present conditions, indicating a different mechanism of action. These results lay the foundation of the avenue for repurposing tolperisone as an analgesic drug to relieve neuropathic pain.
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