Low-dose lidocaine reduces secondary hyperalgesia by a central mode of action

Sodium channel blockers are approved for intravenous administration in the treatment of neuropathic pain states. Preclinical studies have suggested an tihyperalgesic effects on the peripheral as well as the central nervous sys tem. The objective of this study was to determine mechanisms of action of l ow-dose Lidocaine in experimental induced, secondary hyperalgesia. In a fir st experimental trial, participants (n = 12) received lidocaine systemicall y (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusi on of 2 mg kg(-1) h(-1) for another 50 min). In a second trial, a modified intravenous regional anesthesia (IVRA) was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 mi lidocaine, 0.05%; in the other arm 40 mi NaCl, 0.9%, served as a contro l. In both trials capsaicin, 20 mu g, was injected intradermally and time c ourse of capsaicin-induced pain, allodynia and hyperalgesia as well as axon reflex flare was determined. The capsaicin-induced pain was slightly reduc ed after systemic and regional application of the anesthetic. The area of p in-prick hyperalgesia was significantly reduced by systemic lidocaine, wher eas the inhibition of hyperalgesia was absent during regional administratio n of lidocaine. In contrast, capsaicin-induced flare was significantly decr eased after both treatments. We conclude that systemic lidocaine reduces pi n-prick hyperalgesia by a central mode of action, which could involve block ade of terminal branches of nociceptors. A possible role for tetrodotoxin r esistant sodium channels in the antihyperalgesic effect of low-dose lidocai ne is discussed. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. Al rights reserved.