Concentration-effect relations for intravenous lidocaine infusions in human volunteers: effects on acute sensory thresholds and capsaicin-evoked hyperpathia.
BACKGROUND
Preclinical studies have emphasized that persistent small afferent input will induce a state of central facilitation that can be regulated by systemically administered lidocaine. The authors extended these preclinical studies to human volunteers by examining the concentration-dependent effects of intravenous lidocaine on acute sensory thresholds and facilitated processing induced by intradermal capsaicin.


METHODS
Fifteen healthy persons received a lidocaine or a placebo infusion. A computer-controlled infusion pump targeted sequential stepwise increases in plasma lidocaine concentration steps of 1, 2, and 3 microg/ml. At each plasma concentration, neurosensory testing (thermal and von Frey hair test stimulation) were performed. After completing the tests at the 3 microg/ml plasma lidocaine level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair stimulation, stroking, and heat was assessed.


RESULTS
The continuous infusion of lidocaine and placebo had no significant effect on any stimulus threshold. Although intravenous lidocaine resulted in a decrease in all secondary hyperalgesia responses, this was only significant for heat hyperalgesia. Intravenous lidocaine resulted in a significant decrease in the flare response 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 components of nociceptive processing that are different from those associated with the pain state evoked by "acute" thermal or mechanical stimuli. Such insight may be valuable in the efficient development of novel analgesics for both neuropathic and post-tissue-injury pain states.
Wallace
M S
MS
Department of Anesthesiology, University of California, San Diego School of Medicine, 92103, USA.
Laitin
S
S
Licht
D
D
Yaksh
T L
TL
D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D010919:Placebos; D012684:Sensory Thresholds / Q000187:drug effects*; D012881:Skin Temperature / Q000187:drug effects / Q000502:physiology
D000779:Anesthetics, Local; D010919:Placebos; D008012:Lidocaine; D002211:Capsaicin