<p><strong>Menthol</strong>&nbsp;primarily activates the cold-sensitive TRPM8 receptors in the skin. Menthol, after topical application, causes a feeling of coolness due to stimulation of &#39;cold&#39; receptors by inhibiting Ca++&nbsp;currents of neuronal membranes. It may also yield analgesic properties via kappa-opioid receptor agonism.<br />
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<strong>Pramocaine</strong>&nbsp;reversibly binds and inhibits voltage gated sodium channels on neurons decreasing sodium permeability into the cell. This stabilizes the membrane and prevents ionic fluctuations needed for depolarization stopping any action potential propagation.<br />
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Menthol and pramoxine: Each of these agents elicits local anesthetic effects.</p>