Experimental incision-induced pain in human skin: effects of systemic lidocaine on flare formation and hyperalgesia.
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 secondary hyperalgesia was temporary suggests that the development and maintenance of secondary hyperalgesia are caused by different mechanisms.
Kawamata
Mikito
M
Department of Anesthesiology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Hokkaido, Japan. mikitok@sapmed.ac.jp
Takahashi
Toshiyuki
T
Kozuka
Yuji
Y
Nawa
Yuko
Y
Nishikawa
Kohki
K
Narimatsu
Eichi
E
Watanabe
Hiroaki
H
Namiki
Akiyoshi
A
D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy* / Q000503:physiopathology; D012867:Skin / Q000293:injuries*
D000779:Anesthetics, Local; D008012:Lidocaine