Journal article
Central Mechanisms of Menthol-Induced Analgesia
The Journal of pharmacology and experimental therapeutics, v 343(3), pp 661-672
01 Dec 2012
PMID: 22951274
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Menthol is one of the most commonly used chemicals in our daily life, not only because of its fresh flavor and cooling feeling but also because of its medical benefit. Previous studies have suggested that menthol produces analgesic action in acute and neuropathic pain through peripheral mechanisms. However, the central actions and mechanisms of menthol remain unclear. Here, we report that menthol has direct effects on the spinal cord. Menthol decreased both ipsilateral and contralateral pain hypersensitivity induced by complete Freund's adjuvant in a dose-dependent manner. Menthol also reduced both first and second phases of formalin-induced spontaneous nocifensive behavior. We then identified the potential central mechanisms underlying the analgesic effect of menthol. In cultured dorsal horn neurons, menthol induced inward and outward currents in a dose-dependent manner. The menthol-activated current was mediated by Cl- and blocked by bicuculline, suggesting that menthol activates gamma-aminobutyric acid type A receptors. In addition, menthol blocked voltage-gated sodium channels and voltage-gated calcium channels in a voltage-, state-, and use-dependent manner. Furthermore, menthol reduced repetitive firing and action potential amplitude, decreased neuronal excitability, and blocked spontaneous synaptic transmission of cultured superficial dorsal horn neurons. Liquid chromatography/tandem mass spectrometry analysis of brain menthol levels indicated that menthol was rapidly concentrated in the brain when administered systemically. Our results indicate that menthol produces its central analgesic action on inflammatory pain probably via the blockage of voltage- gated Na+ and Ca2+ channels. These data provide molecular and cellular mechanisms by which menthol decreases neuronal excitability, therefore contributing to menthol-induced central analgesia.
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Details
- Title
- Central Mechanisms of Menthol-Induced Analgesia
- Creators
- Rong Pan - Drexel UniversityYuzhen Tian - Drexel UniversityRuby Gao - Drexel UniversityHaitao Li - Nanjing UniversityXianguo Zhao - 3 PharmaOn, LLCJames E. Barrett - Drexel UniversityHuijuan Hu - Drexel University
- Publication Details
- The Journal of pharmacology and experimental therapeutics, v 343(3), pp 661-672
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- Number of pages
- 12
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; Neurology
- Web of Science ID
- WOS:000311099300013
- Scopus ID
- 2-s2.0-84869230595
- Other Identifier
- 991019167600604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy