C-fiber spontaneous discharge evoked by chronic inflammation is suppressed by a long-term infusion of lidocaine yielding nanogram per milliliter plasma levels

Abstract

Nociceptors innervating inflamed tissue acquire an abnormal spontaneous discharge that is believed to be at least part of the reason for the persistent spontaneous pain, allodynia, and hyperalgesia that accompany inflammation. Recent studies suggest that patients with chronic inflammatory pain may obtain an analgesic effect with transdermal application of lidocaine that yields very low plasma levels (130-225 ng/ml). The aim of this study was to investigate whether a 7-day exposure to such low plasma levels of lidocaine had an effect on inflammation-evoked spontaneous discharge in the rat. Seven days after a hind-paw injection of Complete Freund's Adjuvant (CFA), we confirmed the presence of myositis, pain hypersensitivity, and a significant increase in the incidence of spontaneous discharge in A-fibers and C-fibers innervating both muscle and skin. We then compared the incidence of spontaneous discharge in muscle and cutaneous fibers in CFA-injected animals treated with a 7-day infusion of saline or lidocaine. The lidocaine infusion yielded a plasma level of 210 ng/ml. The muscle C-fiber discharge was completely inhibited by the lidocaine infusion and the cutaneous C-fiber discharge was suppressed by 50%. Lidocaine infusion had no effect on the incidence of spontaneous discharge in muscle or cutaneous A-fibers. Lidocaine infusion reduced mechano-hyperalgesia but had no effect on mechano-allodynia or heat-hyperalgesia. We conclude that the analgesic effects seen clinically with transdermal lidocaine administration yielding low plasma levels may be due to a systemic drug action on spontaneously active C-fibers.