The effects of intradermal fentanyl and ketamine on capsaicin-induced secondary hyperalgesia and flare reaction

In this study, we evaluated the effects of intradermal fentanyl and ketamin e on capsaicin-induced hyperalgesia and axon-reflex flare. In addition, we obtained dose-response curves for possible local anesthetic effects. Saline (200 mu L) and either fentanyl (1 mu g or 10 mu g in 200 mu L) or ketamine (100 mu g or 1000 mu g in 200 mu L) were injected simultaneously into the central volar forearm of 12 healthy volunteers. Nine minutes later, capsaic in (10 mu g in 20 mu L) was injected intracutaneously exactly between the t wo injection sites. Areas of touch-evoked allodynia and pinprick hyperalges ia, as well as intensity of pinprick hyperalgesia at the injection sites an d axon-reflex flare, were evaluated. Fentanyl did not affect the area or in tensity of secondary hyperalgesia. Only the larger concentration of fentany l locally diminished axon-reflex flare without affecting mechanical detecti on thresholds. Inhibitory effects of ketamine on intensity of secondary hyp eralgesia and axon reflex flare were observed only in the larger concentrat ion. However, this concentration also clearly elevated mechanical detection thresholds. No inhibitory effects of ketamine in the smaller concentration s 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 lon g as nonlocal anesthetic concentrations were applied. Implications: We inve stigated the peripheral effects of fentanyl and ketamine on capsaicin-induc ed 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.