The systemic local anaesthetics that are commonly used include lidocaine, tocainide and mexiletine (oral analogue of lidocaine). The assumed mechanism of action to effect analgesia is the acute blocking of sodium channels. Phenytoin, carbamazepine and tricyclic antidepressants (TCAs) also act as sodium channel blockers. Following the use of TCAs and anticonvulsants, local anaesthetics tend to be third-line drugs.
Lidocaine has proven effective for non-cancer patients, but not for those with cancer. In cancer patients, tumour involvement of nervi nervorum with "nociceptive neuropathic pain" may represent a different mechanism, with variable response to therapy. Recent studies have suggested that the duration and pattern of spontaneous discharge is dependent on the level and kinetics of Na+ slow channel inactivation. Slow inactivation of voltage-gated ion channels could be major factors in the induction and treatment of neuropathic pain.
Dosing of mexiletine is begun at 150 mg po qds and is slowly escalated up to a maximum of 10 mg/kg/day as tolerated. The only absolute contraindication to the use of mexiletine is pre–existing second- or third-degree atrioventricular block or known allergy to the medication.