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.

Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

“…Similarly to a previous experiment employing similar stimuli (Lötsch et al, 2012), the nociceptive stimuli were always perceived as painful (median [interquartile range]: 48.63 [33.19, 67.44] mm VAS pain) but not smelly (0 [0.0, 6.31] mm VAS smell), whereas the H 2 S and vanillin were rated as smelly (31.44 [19.43, 47.5] and 22.06 [9.0, 31.9] mm VAS smell, respectively) but not painful (0 [0.0, 0.0] mm VAS pain). THC altered neither intensity perception (interaction 'drug' by 'measurement': F(1,14) = 3.16, p = 0.097) nor pleasantness rating (interaction 'drug' by 'measurement': F(1,14) = 0.391, p = 0.542) of the painful CO 2 stimuli.…”

Framing the ultimatum game: the contribution of simulation

“…Based on previous neuroimaging studies on the framing effect described in the introduction (De Martino et al, 2006), we hypothesized that emotional areas such as anterior insula and amygdala, were involved in processing the frame; moreover, further imaging studies reported activations in the operculo/insular cortex associated with pain processing (e.g., Lötsch et al, 2012) and in interoceptive awareness and the representation of visceral responses associated with emotional situations (Lamm et al, 2007). Thus, a hypothesis-driven region of interest (ROI) analysis (Friston, 1997) was performed in which we tested significant increases of neural activity in the operculo/insular cortex [Anatomy Toolbox (Eickhoff et al, 2005)], for the main effect of frame.…”

Using Functional Magnetic Resonance Imaging to Determine if Cerebral Hemodynamic Responses to Pain Change Following Thoracic Spine Thrust Manipulation in Healthy Individuals

“…1,10,49 Additional research has revealed that functional areas associated with the pain matrix may also be activated in response to nonpainful stimuli. 2,36,46 This may be directly re-…”

“…36 It has also been proposed that areas within the pain matrix may include an evaluative component to discern whether the sensory input is potentially threatening. 33,45 We hypothesized that a change in cerebral blood flow, in the form of decreased activation of the areas associated with pain perception, would occur following thrust manipulation to the thoracic spine, and a significant relationship would exist between reduction in pain perception and change in cerebral activation.…”