title: The effect of Ketamine on stimulation of primary and secondary hyperalgesic areas induced by capsaicin--a double-blind, placebo-controlled, human experimental study.
abstract: The non-competitive NMDA-antagonist, Ketamine, was infused (i.v.) in healthy volunteers to study the effect on central excitability with the presence of cutaneous hyperalgesia. Hyperalgesia was established experimentally on the dorsum of the foot by topical application of capsaicin (1%). Different thermal and mechanical conditioning stimuli were applied to the primary and secondary hyperalgesic areas to modulate the central nociceptive excitability monitored by the nociceptive reflex. When the elicited reflex was combined with an activation of the secondary hyperalgesic area by continuous, non-painful, electrical stimulation, a facilitation of the reflex was observed. This indicates that summation of activity in non-nociceptive and nociceptive afferents can occur under mild pathological conditions. Conditioning thermal stimuli of the primary hyperalgesic area were employed to intensify the allodynia prior to testing this interaction between tactile and nociceptive activity. The same reflex facilitation was inhibited by Ketamine. Furthermore, Ketamine decreased the pain intensity associated with the stimuli eliciting the reflex. Psychophysical measures to single and repeated electrical and thermal (laser) stimuli applied within the hyperalgesic areas were also obtained. The intensity of pain sensations produced by single, painful, electrical stimuli applied to the primary hyperalgesic region was reduced after Ketamine infusion. Finally, five repeated, electrical stimuli applied to the secondary hyperalgesic area were used to assess the temporal summation threshold. Ketamine caused an increase in the summation threshold compared to the placebo treatment. In conclusion, these results demonstrate that (1) summation of activity in non-nociceptive and nociceptive afferents occurs under hyperalgesic conditions and, (2) this summation can be inhibited by NMDA-antagonists. Therefore, the study shows an apparent involvement of NMDA-receptors in some of the central mechanisms underlying secondary hyperalgesia.
authors.affiliation: Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Frederik Bajers Vej 7D,DK-9220 Aalborg,Denmark Department of Anaesthesiology, Aarhus Univrrsity Hospital,Århus,Denmark Department of Neurology, Pain Research Center, Aarhus University Hospital,Århus,Denmark Department of Dermatology, Marselisborg Hospital,Århus,Denmark.
authors.forename: Ole Kæseler
authors.initials: OK
authors.lastname: Andersen
authors.forename: Sven
authors.initials: S
authors.lastname: Felsby
authors.forename: Lone
authors.initials: L
authors.lastname: Nicolaisen
authors.forename: Peter
authors.initials: P
authors.lastname: Bjerring
authors.forename: Troels Staehelin
authors.initials: TS
authors.lastname: Jensen
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
mesh_terms: D000328:Adult; D000778:Anesthetics, Dissociative / Q000009:adverse effects / Q000494:pharmacology*; D002211:Capsaicin; D004311:Double-Blind Method; D004558:Electric Stimulation; D004594:Electrophysiology; D006181:H-Reflex; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D007649:Ketamine / Q000009:adverse effects / Q000494:pharmacology*; D007834:Lasers; D009619:Nociceptors / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold; D010919:Placebos; D011601:Psychophysics / Q000379:methods; D011930:Reaction Time
chemical_list: D000778:Anesthetics, Dissociative; D010919:Placebos; D007649:Ketamine; D002211:Capsaicin