Sodium channel blockers in neuropathic pain

• Published in: Current pharmaceutical design Vol. 11; no. 23; p. 3005
• Main Author: Kalso, Eija
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-09-2005
• Subjects: Anesthetics, Local - pharmacology; Anesthetics, Local - therapeutic use; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Humans; Pain - drug therapy; Pain - etiology; Pain - physiopathology; Peripheral Nervous System Diseases - complications; Sodium Channel Blockers - therapeutic use; Sodium Channels - physiology
• ISSN: 1381-6128
• DOI: 10.2174/1381612054865028

Subtypes of tetrodotoxin resistant voltage-gated sodium channels are involved in the development of certain types of neuropathic pains. After nerve injury hyperexcitability and spontaneous firing develop at the site of injury and also in the dorsal root ganglion cell bodies. This hyperexcitability results at least partly from accumulation of sodium channels at the site of injury. The facts that these sodium channels seem to exist in peripheral nerves only and that they can be blocked at the resting state (use-dependent block) offer the possibility to develop drugs, which selectively block these damaged, overexcited nerves. At the moment no such drugs are available. However, some of the most potent drugs that are currently used to manage neuropathic pain e.g. amitriptyline and other tricyclic antidepressants, also block these channels in addition to having several other mechanisms of action. Also most anticonvulsants that are used to alleviate neuropathic pain are sodium channel blockers. Lidocaine, the prototype drug, has been shown to be effective in peripheral neuropathic pain. Its use is limited by the fact that it cannot be administered orally. An oral local anesthetic type sodium channel blocker, mexiletine is an antiarrhythmic agent that is effective in neuropathic pain. However, effective doses may be difficult to achieve because of adverse effects.