Summary
In conclusion the TTX-resistant sodium current, especially that produced by the NaV1.8 subunit, appears to be a strong candidate for a molecular substrate underlying sensitization of visceral afferent nociceptive neurons.
The visceral anti-nociceptive effects of agents that block sodium currents confirm an important role for these channels in visceral sensation. Intravenous lidocaine, a use-dependent sodium channel blocker, is effective in inhibiting both pseudoaffective reflex responses and spinal neuronal discharges to noxious distension of the colon [32]. Likewise, the sodium channel blockers mexiletine and carbamazepine dose-dependently inhibit the responses of nociceptive colonic afferent fibres to colorectal distension [33]. There have been very few clinical reports of the effects of sodium channel blockers on visceral pain [32, 34] although one report describes that systemic local anaesthetics were effective in relieving pain from the spleen [35]. However, indirect evidence comes from the observation that tricyclic antidepressant drugs like amitriptyline are regularly prescribed for functional visceral pain. Although these compounds likely exert their antidepressant effects by blocking the re-uptake of monoamines, many are also potent sodium channel blockers, and this feature may contribute to their effectiveness in some visceral pain patients.
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Laird, J.M., Cervero, F., Laird, J.M. (2005). Voltage-gated sodium channels and visceral pain. In: Parnham, M.J., Coward, K., Baker, M.D. (eds) Sodium Channels, Pain, and Analgesia. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7411-X_3
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