Different Mechanisms of Development and Maintenance of Experimental Incision-induced Hyperalgesia in Human Skin

Background To determine the mechanisms of postoperative pain, the effects of local anesthesia on development and maintenance of surgical incision-induced hyperalgesia were evaluated in a crossover, double-blinded, placebo-controlled human study using 17 subjects. Methods An experimental 4-mm-long incision through skin, fascia, and muscle was made in the volar forearm of each subject. In experiment 1, 1% lidocaine or saline in a volume of 0.2 ml was subcutaneously injected into the incision site pretraumatically and posttraumatically. In experiment 2, a 5-cm-long strip of skin was subcutaneously injected with 0.2 ml of 1% lidocaine near the incision site pretraumatically and posttraumatically. Flare, spontaneous pain, and primary and secondary hyperalgesia to punctate mechanical stimuli were assessed after the incision had been made. Results Pretraumatic lidocaine injection prevented the occurrence of spontaneous pain and development of flare formation that was found surrounding the incision site immediately (1 min) after the incision had been made. The lidocaine suppressed primary hyperalgesia more effectively than did posttraumatic block, but only for the first 4 h after the incision. The preincision block prevented development of secondary hyperalgesia, whereas posttraumatic block did not significantly affect the fully developed secondary hyperalgesia. The area of flare formation and the area of secondary hyperalgesia did not extend over the strip of the skin that had been pretraumatically anesthetized, whereas the posttraumatic block did not significantly reduce the area of fully developed secondary hyperalgesia. Conclusions Pretraumatic injection of lidocaine reduces primary hyperalgesia more effectively than does posttraumatic injection, but only for a short period after incision. The spread of secondary hyperalgesia is mediated peripheral nerve fibers, but when secondary hyperalgesia has fully developed, it becomes less dependent on or even independent of peripheral neural activity originating from the injured site.