title: The human operculo-insular cortex is pain-preferentially but not pain-exclusively activated by trigeminal and olfactory stimuli.
abstract: Increasing evidence about the central nervous representation of pain in the brain suggests that the operculo-insular cortex is a crucial part of the pain matrix. The pain-specificity of a brain region may be tested by administering nociceptive stimuli while controlling for unspecific activations by administering non-nociceptive stimuli. We applied this paradigm to nasal chemosensation, delivering trigeminal or olfactory stimuli, to verify the pain-specificity of the operculo-insular cortex. In detail, brain activations due to intranasal stimulation induced by non-nociceptive olfactory stimuli of hydrogen sulfide (5 ppm) or vanillin (0.8 ppm) were used to mask brain activations due to somatosensory, clearly nociceptive trigeminal stimulations with gaseous carbon dioxide (75% v/v). Functional magnetic resonance (fMRI) images were recorded from 12 healthy volunteers in a 3T head scanner during stimulus administration using an event-related design. We found that significantly more activations following nociceptive than non-nociceptive stimuli were localized bilaterally in two restricted clusters in the brain containing the primary and secondary somatosensory areas and the insular cortices consistent with the operculo-insular cortex. However, these activations completely disappeared when eliminating activations associated with the administration of olfactory stimuli, which were small but measurable. While the present experiments verify that the operculo-insular cortex plays a role in the processing of nociceptive input, they also show that it is not a pain-exclusive brain region and allow, in the experimental context, for the interpretation that the operculo-insular cortex splay a major role in the detection of and responding to salient events, whether or not these events are nociceptive or painful.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany. j.loetsch@em.uni-frankfurt.de
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
authors.forename: Carmen
authors.initials: C
authors.lastname: Walter
authors.forename: Lisa
authors.initials: L
authors.lastname: Felden
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nöth
authors.forename: Ralf
authors.initials: R
authors.lastname: Deichmann
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Oertel
mesh_terms: D000328:Adult; D001547:Benzaldehydes / Q000494:pharmacology; D001931:Brain Mapping / Q000379:methods; D002245:Carbon Dioxide / Q000494:pharmacology; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009812:Odorants; D055696:Olfactory Perception / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D013003:Somatosensory Cortex / Q000503:physiopathology*; D014276:Trigeminal Nerve / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D001547:Benzaldehydes; D002245:Carbon Dioxide; C100058:vanillin; D006862:Hydrogen Sulfide