The Effects of Intradermal Fentanyl and Ketamine on Capsaicin-Induced Secondary Hyperalgesia and Flare Reaction

Abstract

In this study, we evaluated the effects of intradermal fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In addition, we obtained dose-response curves for possible local anesthetic effects. Saline (200 microL) and either fentanyl (1 microg or 10 microg in 200 microL) or ketamine (100 microg or 1000 microg in 200 microL) were injected simultaneously into the central volar forearm of 12 healthy volunteers. Nine minutes later, capsaicin (10 microg in 20 microL) was injected intracutaneously exactly between the two injection sites. Areas of touch-evoked allodynia and pinprick hyperalgesia, as well as intensity of pinprick hyperalgesia at the injection sites and axon-reflex flare, were evaluated. Fentanyl did not affect the area or intensity of secondary hyperalgesia. Only the larger concentration of fentanyl locally diminished axon-reflex flare without affecting mechanical detection thresholds. Inhibitory effects of ketamine on intensity of secondary hyperalgesia and axon reflex flare were observed only in the larger concentration. However, this concentration also clearly elevated mechanical detection thresholds. No inhibitory effects of ketamine in the smaller concentrations were observed. We conclude that fentanyl inhibits neuropeptide release on peripheral application without modulating secondary hyperalgesia. Ketamine failed to inhibit both secondary hyperalgesia and axon reflex flare as long as nonlocal anesthetic concentrations were applied. We investigated the peripheral effects of fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In large concentrations, the opioid diminished axon-reflex flare without effects on secondary hyperalgesia. We found no evidence for the involvement of endogenous glutamate in secondary hyperalgesia or axon reflex flare.