CONCENTRATION-EFFECT RELATIONS FOR INTRAVENOUS LIDOCAINE INFUSIONS INHUMAN VOLUNTEERS - EFFECTS ON ACUTE SENSORY THRESHOLDS AND CAPSAICIN-EVOKED HYPERPATHIA

Background: Preclinical studies have emphasized that persistent small afferent input mill induce a state of central facilitation that can be regulated by systemically administered lidocaine. The authors extende d these preclinical studies to human volunteers by examining the conce ntration-dependent effects of intravenous lidocaine on acute sensory t hresholds and facilitated processing induced by intradermal capsaicin. Methods: Fifteen healthy persons received a lidocaine or a placebo in fusion, A computer-controlled infusion pump targeted sequential stepwi se increases in plasma lidocaine concentration steps of 1, 2, and 3 mu g/ml. At each plasma concentration, neurosensory testing (thermal and von Frey hair test stimulation) were performed. After completing the tests at the 3 mu g/ml plasma lidocaine level, intradermal capsaicin w as injected into the volar aspect of the left forearm, and the flare r esponse and hyperalgesia to von Frey hair stimulation, stroking, and h eat mas assessed. Results: The continuous infusion of lidocaine and pl acebo had no significant effect on any stimulus threshold. Although in travenous Lidocaine resulted in a decrease in all secondary hyperalges ia responses, this was only significant for heat hyperalgesia. Intrave nous lidocaine resulted in a significant decrease in the flare respons e induced by intradermal capsaicin. Conclusions: These studies suggest that the facilitated state induced by persistent small afferent input human pain models may predict the activity of agents that affect comp onents of nociceptive processing that are different from those associa ted with time pain stale evoked by ''acute'' thermal or mechanical sti muli. Such insight may be variable in the efficient development of nov el analgesics for both neuropathic and post-tissue-injury pain states.