Convergence of sensory and limbic noxious input into the anterior insula and the emergence of pain from nociception

Abstract

Two parallel di-synaptic routes convey nociceptive input to the telencephalon: the spino-thalamic system projecting principally to the posterior insula, and the spino-parabrachial pathway reaching the amygdalar nucleus. Interplay between the two systems underlies the sensory and emotional aspects of pain, and was explored here in humans with simultaneous recordings from the amygdala, posterior and anterior insulae. Onsets of thermo-nociceptive responses were virtually identical in the posterior insula and the amygdalar complex, but no significant functional connectivity was detected between them using coherence analysis. Anterior insular sectors responded with ~30 ms delay relative to both the posterior insula and the amygdala. While intra-insular functional correlation was significant during the whole analysis period, coherence between the anterior insula and the amygdala became significant after 700 ms of processing. Phase lags indicated information transfer initially directed from the amygdalar complex to the insula. Parallel but independent activation of sensory and limbic nociceptive networks appear to converge in the anterior insula in less than one second. While the anterior insula is often considered as providing input into the limbic system, our results underscore its reverse role, i.e., receiving and integrating very rapidly limbic with sensory input, to initiate a perceptual decision on the stimulus ‘painfulness’.

The Reorganization of Insular Subregions in Individuals with Below-Level Neuropathic Pain following Incomplete Spinal Cord Injury

“…However, recent neuroimaging evidences suggested the disparate functions ascribed to the insula in the perception of pain [25,44]. In our present FC analysis, we found there was no statistical difference with right insula as seeds.…”

“…The hippocampus is possibly involved in the formation of pain-associated memory and emotional responses [67,68]. Earlier researches have proposed that the sensory and limbic networks of pain are parallel and independent [25]. Follows a nociceptive stimulation, an initial noxious processing in sensory and limbic systems is rapidly followed by a functional integration of both toward the AI.…”

“…Furthermore, the increased insular cerebral blood flow (CBF) was highly correlated with pain intensity [20,21]. Therefore, the changes in insular morphology and function are inevitably associated with pain after SCI, while the anterior and posterior of insula differ in cytoarchitecture and function [22,23], the subregions of insula have been implicated in the different functional profiles in the perception of pain [11,24,25]. The anterior insula (AI) principally receives afferent from the medial nuclei of the thalamus [26] and is interconnected with the ventrolateral prefrontal and orbitofrontal cortex, which is associated with the cognitiveaffective components of nociceptive processing [11].…”

Perception of phasic pain is modulated by smell and taste

“…These brain areas have been shown to be involved in elaborating emotions (Chang, Yarkoni, Khaw, & Sanfey, ; Craig, ; Smith & Lane, ; Wiech et al, ). It was recently demonstrated that the anterior insula could be considered as a “hub” integrating the sensory and emotional aspects of pain (Bastuji, Frot, Perchet, Hagiwara, & Garcia‐Larrea, ). More precisely, in the initial processing of a noxious stimulus, the sensory and limbic systems work uncorrelated and in parallel; afterwards the two systems functionally convergence toward the anterior insula, thus contributing to a unified subjective experience of pain, that integrates the sensory and emotional aspects (Bastuji et al, ).…”

“…It was recently demonstrated that the anterior insula could be considered as a “hub” integrating the sensory and emotional aspects of pain (Bastuji, Frot, Perchet, Hagiwara, & Garcia‐Larrea, ). More precisely, in the initial processing of a noxious stimulus, the sensory and limbic systems work uncorrelated and in parallel; afterwards the two systems functionally convergence toward the anterior insula, thus contributing to a unified subjective experience of pain, that integrates the sensory and emotional aspects (Bastuji et al, ). These observations are in line with another study indicating the existence of a top‐down prefronto‐insula‐amygdala network regulating negative emotional states (Shiba et al, ).…”