Xenon-induced changes in CNS sensitization to pain.
Electrophysiological investigations of the spinal cord in animals have shown that pain sensitizes the central nervous system via glutamate receptor dependent long-term potentiation (LTP) related to an enhancement of pain perception. To expand these findings, we used functional magnetic resonance (fMRI), blood oxygen level dependent (BOLD) and perfusion imaging in combination with repeated electrical stimulation in humans. Specifically we monitored modulation of somatosensory processing during inhibition of excitatory transmission by ocular application of the glutamate receptor antagonist xenon. BOLD responses upon secondary stimulation increased in mid insular and in primary/secondary sensory cortices under placebo and decreased under xenon treatments. Xenon-induced decreases in regional perfusion were confined to stimulation responsive brain regions and correlated with time courses of xenon concentrations in the cranial blood. Moreover, effects of xenon on behavioral, fMRI and perfusion data scaled with stimulus intensity. The dependence of pain sensitization on sufficient pre-activation reflects a multistage process which is characteristic for glutamate receptor related processes of LTP. This study demonstrates how LTP related processes known from the cellular level can be investigated at the brain systems level.
Adolph
Oliver
O
Department of Anesthesiology, University Hospital of Ulm, Steinhoevelstrasse 9, Ulm, Germany. oliver.adolph@uniklinik-ulm.de
Köster
Sarah
S
Georgieff
Michael
M
Bäder
Stefan
S
Föhr
Karl J
KJ
Kammer
Thomas
T
Herrnberger
Bärbel
B
Grön
Georg
G
D000328:Adult; D018685:Anesthetics, Inhalation / Q000097:blood / Q000494:pharmacology*; D001784:Blood Gas Analysis; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004311:Double-Blind Method; D004558:Electric Stimulation; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000523:psychology*; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012677:Sensation / Q000502:physiology; D013003:Somatosensory Cortex / Q000502:physiology; D014978:Xenon / Q000097:blood / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon; D010100:Oxygen