IN-VIVO IMAGING OF NITROUS OXIDE-INDUCED CHANGES IN CEREBRAL ACTIVATION DURING NOXIOUS HEAT STIMULI

Background: Although previous studies have provided some insight into the pharmacologic aspects of nitrous oxide analgesia, the neural circu its mediating its antinociceptive effect remain relatively unexplored. Positron emission tomography was used in nine volunteers to identify the loci of nitrous oxide-modulated cerebral responses to a peripheral noxious stimulus. Methods: Nitrous oxide-pain interactions were studi ed by comparing regional cerebral blood flow responses to a 48 degrees C tonic heat stimulus, applied to each volunteer's left forearm, duri ng room air inhalation with those obtained while 20% nitrous oxide was administered. Two cerebral blood flow scans were obtained with the O- 15-water technique during each condition. Locations of specific region al activation related to pain, and nitrous oxide, were identified usin g the statistical parametric mapping method, with a significance level of P < 0.01. Pain was rated by visual analog scale and the values wer e compared using Wilcoxon rank sum analysis. Results: Pain produced ce rebral activation in the contralateral thalamus, anterior cingulate, a nd supplementary motor area. Adding nitrous oxide during pain stimulat ion abolished activation in these areas but was associated with activa tion in the contralateral infralimbic and orbitofrontal cortices. In p arallel, mean visual analog scale scores decreased significantly from 67 +/- 4 (SEM) to 54 +/- 5 (P < 0.05), Conclusions: Nitrous oxide, at 20% concentration, appears to modulate pain processing in the brain's medial pain system, and also activates the infralimbic and orbitofront al cortices. The potential contribution of the affected brain areas to nitrous oxide analgesia is discussed.