Effect of pre- or post-traumatically applied i.v. lidocaine on primary and secondary hyperalgesia after experimental heat trauma in humans.
Hyperalgesia on intradermal capsaicin application can be attenuated by systemic application of local anesthetics. We tested whether low doses of local anesthetics applied pre- or post-traumatically can reduce heat trauma-induced primary and secondary hyperalgesia in humans. Six healthy volunteers consented to the randomized, double-blind, and cross-over designed study. In each subject, a first-degree burn injury was induced three times (corresponding to a pre-traumatic, post-traumatic and control group) at an interval of at least 3 weeks. Heat was applied by a computer-controlled Peltier thermode (47 degrees C, 5 min). In the pre-traumatic group, lidocaine infusion was commenced 30 min prior to heat trauma, and in the post-traumatic group immediately after heat trauma for a total infusion time of 60 min each. Volunteers rated pain on a visual analogue scale (VAS) between threshold and tolerance maximum (0-100% VAS). Primary hyperalgesia was quantified by determining mechanical (von Frey hairs) and thermal (Peltier thermode) pain thresholds. Secondary hyperalgesia was quantified by determining the area in which normally unpleasant von Frey hairs evoked pain or tenderness. Baseline thermal and mechanical pain thresholds did not differ between groups. Heat application always resulted in a first-degree burn injury including both primary and secondary hyperalgesia. The former remained by and large stable for about 4 h whereas the latter continuously increased within the first 2 h. Lidocaine did not affect primary hyperalgesia, irrespective of pre- or post-traumatic application, but substantially reduced the development of secondary hyperalgesia on pre-traumatic, and for tendency on post-traumatic infusion (treatment groups did not differ significantly). Burn injury-induced erythema was smallest in the pre-traumatic group and largest in the control group; however, the level of significance was not reached. Plasma concentrations of lidocaine were always higher than 1.5 microg/ml 30 min after bolus application of lidocaine and reached a peak of 2-3 microg/ml after about 1 h. Thus, local anesthetics at concentrations that do not block nerve conduction substantially affect ongoing central changes in pain processing that are induced by a real tissue trauma. A significant preemptive effect could not be demonstrated. The anti-hyperalgesic effect of lidocaine is likely based on action of central (spinal) sites, but peripheral sites may also be addressed.
Holthusen
Holger
H
Department of Anaesthesiology, Heinrich-Heine-University, Duesseldorf, Germany.
Irsfeld
Stefan
S
Lipfert
Peter
P
D000328:Adult; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002056:Burns / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D008012:Lidocaine / Q000008:administration & dosage*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects*; D018709:Statistics, Nonparametric; D014947:Wounds and Injuries / Q000188:drug therapy
D000779:Anesthetics, Local; D008012:Lidocaine