Experimental incision-induced pain in human skin: effects of systemic lidocaine on flare formation and hyperalgesia

Abstract

In order to try to gain a better understanding of the mechanisms of post-operative pain, this study was designed to psychophysically determine physiological and pharmacological characteristics of experimental pain induced by a 4-mm-long incision through the skin, fascia and muscle in the volar forearm of humans. In experiment 1, the subjects (n=8) were administered lidocaine systemically (a bolus injection of 2mg/kg for a period of 5 min followed by an intravenous infusion of 2mg/kg/h for another 40 min), and then the incision was made. In experiment 2, cumulative doses of lidocaine (0.5-2mg/kg) were systemically injected in the subjects (n=8) 30 min after the incision had been made, when primary and secondary hyperalgesia had fully developed. Spontaneous pain was assessed using the visual analog scale (VAS). Primary hyperalgesia was defined as mechanical pain thresholds to von Frey hair stimuli (from 7 to 151 mN) in the injured area. The area of secondary hyperalgesia to punctate mechanical stimuli was assessed using a rigid von Frey hair (151 mN). Flare formation was assessed in the first experiment using a laser doppler imager (LDI). Pain perception was maximal when the incision was made and then rapidly disappeared within 30 min after the incision had been made. Primary hyperalgesia was apparent at 15 min after the incision had been made and remained for 2 days. The incision resulted in a relatively large area of flare formation immediately after the incision had been made. The area of flare began to shrink within 15 min and was limited to a small area around the injured area at 30 min after incision. Secondary hyperalgesia was apparent at 30 min after incision and persisted for 3h after incision and then gradually disappeared over the next 3h. In experiment 1, pre-traumatic treatment with systemic lidocaine suppressed primary hyperalgesia only during the first 1h after the incision had been made. The lidocaine suppressed the development of flare formation without affecting the pain rating when the incision was made. The development of secondary hyperalgesia continued to be suppressed after completion of the lidocaine infusion. In experiment 2, post-traumatic treatment with lidocaine temporarily suppressed primary as well as secondary hyperalgesia that had fully developed; however, the primary and secondary hyperalgesia again became apparent after completion of the lidocaine administration. These findings suggest that pre-traumatic treatment with lidocaine reduces the excessive inputs from the injured peripheral nerves, thus suppressing development of flare formation and secondary hyperalgesia through peripheral and central mechanisms, respectively. Pre-traumatic treatment with lidocaine would temporarily stabilize the sensitized nerves in the injured area, but the nerves would be sensitized after completion of the administration. Post-traumatic treatment with lidocaine reduced primary and secondary hyperalgesia that had fully developed. However, the finding that the suppressive effect of lidocaine on seconda...

Modality-specific Somatosensory Changes in a Human Surrogate Model of Postoperative Pain

“…In an area surrounding the site of incision we found increased pain to pinprick stimuli (secondary mechanical hyperalgesia), which confirms previous reports after incision in humans 23,24 and after other types of actual or simulated tissue injuries in volunteers. 16,28 -32 Hyperalgesia secondary to mechanical stimuli is considered the perceptual correlate of central sensitization in humans.…”

“…[23][24][25] As shown recently 26,27 spontaneous activity in sensitized C-and A␦-fiber nociceptive afferents induced by deep-tissue (muscle and/or fascia) injury has been suggested as a major contributor to nonevoked ongoing pain after incision in rats. However, the different role of cutaneous and muscle tissue injury to spontaneous pain after incision was not addressed here.…”

“…The apparent biphasicity within the first hour has not yet been described in models of incisional pain, maybe because ongoing pain has not yet been investigated in this temporal resolution. [23][24][25] However, because the reincrease did not reach statistical significance further studies with larger groups of subjects have to address this issue in future studies.…”

Intraperitoneal and intravenous lidocaine for effective pain relief after laparoscopic appendectomy: a prospective, randomized, double-blind, placebo-controlled study

“…The analgesic effect of systemic lidocaine is biphasic. It has a peripheral suppression effect on acute chemically induced pain [27,28], and also a central antihyperalgesic effect [29,30]. Its modes of action have been studied and it is assumed that systemic lidocaine mediates various actions, including sodium channel blockade [14], muscarinic receptor blockade [31], N-methyl-D-aspartate (NMDA) receptor blockade [32] and inhibition of polymorphonuclear leukocyte priming and activation [33].…”

Lidocaine Infusion as a Rescue Analgesic in the Perioperative Setting

“…Suggested additional mechanisms include the ability of lidocaine to inhibit flare formation and hyperalgesia secondary to experimental incision-induced pain (9). Further research has suggested that the mechanism of action may in part be associated with N-methyl-D-aspartate receptor antagonism (10).…”