The effect of intradermal administration of lidocaine plus sufentanil on the response to thermal stimulation

Introduction: Opioid receptors in peripheral tissues may result in anti-nociceptive effects when occupied by opioids (1). In a previous study involving pain responses to thermal stimulation, an intradermal combination of morphine plus lidocaine produced hyperalgesia, rather than analgesia. The authors (2) hypothesized that the reason for hyperalgesia was the release of histamine by morphine at the site of injection. The purpose of the present investigation was to determine whether the combination of lidocaine plus an opioid devoid of histamine-releasing properties (sufentanil) would provide superior analgesia than lidocaine alone. Methods: Following IRB approval, nine healthy volunteers where instructed in the method of magnitude estimation of pain. The volunteers underwent baseline pre-injection testing at 5 sites on both volar forearms with 7-sec thermal stimuli in 2°C increments, between 44 and 32 C, delivered in random sequence. The pain elicited by each stimulus was recorded and normalized to the subjects' response to 50°C at the reference site. Following baseline testing, four of the sites were randomly assigned to receive equal volumes (0.1 ml) of either normal saline, lidocaine 0.5%, sufentanil 0.7 meg or lidocaine 0.5% plus sufentanil 0.75 meg via intradermal injection using 27g tuberculin needles. One site did not receive an injection (reference site). At 6, 30, 60, 90,120, and 150 min following injection, thermal testing was repeated. The normalized pain responses at the five sites during a given phase were compared using analysis of variance with correction for multiple comparison. P<0.05 was considered statistically significant. Results: Baseline testing showed no differences among the five testing sites. Six minutes after injection, the lidocaine only and sufentanil plus lidocaine sites had overall mean pain scores that were 79% and 86% lower, respectively, than the reference site (p<0.05). Pain at the lidocaine plus sufentanil site was 6% lower than at the lidocaine-only site (p=ns). Thirty minutes following injection, analgesia at the lidocaine and lidocaine plus sufentanil site had recovered to 29% and 38% of the reference site (p=ns). At 30-min after injection, five of the nine volunteers had less pain at the lidocaine plus sufentanil site, and four at the lidocaine-only site, respectively. Discussion: The findings of this investigation suggest that the intradermally applied combination of lidocaine plus sufentanil does not significantly prolong the analgesic effect of this local anesthetic. In contrast to inflammation and hyperosmolar compounds (3), lidocaine does not seem to make opioids accessible to peripheral opioid receptors. Due to the low amount of sufentanil administered in this model, systemic effects can be virtually excluded.