Systemic Local Anesthetics for Neuropathic Pain (also see Chapter 72 )

A broad variety of local anesthetics, antiarrhythmics, anticonvulsants, and other Na⁺ channel blockers are administered intravenously and orally to relieve neuropathic pain. Allodynia, causalgia, and other sensory disturbances from nerve injury, diabetes, and herpes infection have all been treated by such drugs, but with variable success. Clinical results are unpredictable. Although successful responses to intravenous lidocaine are often taken as a positive indication for oral mexiletine, many patients find mexiletine difficult to tolerate. When the signs of neuropathic pain are reversed by lidocaine infusion, normal nociception and other sensory modalities are unaffected, thus suggesting that the neurophysiologic correlate of the disease or diseases has an unusually high susceptibility to these drugs, which are present in plasma at concentrations 50 to 100 times lower than those required to block normal impulses in peripheral fibers. Laboratory studies suggest that the ectopic impulse activity that arises at an injury site or elsewhere (e.g., the dorsal root ganglion) contributes to neuropathic pain and that such impulses are particularly sensitive to use-dependent Na⁺ channel blockers. It is noteworthy that relief of preexisting neuropathic pain, both clinically and in animal models,^[97] can in some cases persist for days, weeks, or months after a single intravenous infusion of drug (e.g., lidocaine), far beyond the lifetime of the drug in vivo or of any nerve block that it might effect. The mechanism of this remarkable action remains a mystery.