Insular Cortex is Critical for the Perception, Modulation, and Chronification of Pain

Lu, Changbo; Yang, Tao; Zhao, Huan; Zhang, Ming; Meng, Fan-Cheng; Fu, Hao; Xie, Yingli; Xu, Hui

doi:10.1007/s12264-016-0016-y

Cited by 212 publications

(143 citation statements)

References 99 publications

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“…Interestingly, functional connectivities of somatomotor areas and the insula, as well as visual processing and pain-related areas, were also increased in bad responders at the beginning and the end of the neurofeedback training. It is well known that the insula is involved in sensory and affective dimensions of pain processing and its functional connectivity seems to be impaired in chronic pain leading to a disruption of modulatory circuits involved in pain (Lu et al, 2016). Thus, our findings of an enhanced functional connectivity of these pain-related brain areas in bad responders suggest that patients could be more focused on pain perception, rather than on the neurofeedback task.…”

Section: Discussionmentioning

confidence: 60%

Self-Regulation of SMR Power Led to an Enhancement of Functional Connectivity of Somatomotor Cortices in Fibromyalgia Patients

et al. 2020

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Neuroimaging studies have demonstrated that altered activity in somatosensory and motor cortices play a key role in pain chronification. Neurofeedback training of sensorimotor rhythm (SMR) is a tool which allow individuals to self-modulate their brain activity and to produce significant changes over somatomotor brain areas. Several studies have further shown that neurofeedback training may reduce pain and other pain-related symptoms in chronic pain patients. The goal of the present study was to analyze changes in SMR power and brain functional connectivity of the somatosensory and motor cortices elicited by neurofeedback task designed to both synchronize and desynchronize the SMR power over motor and somatosensory areas in fibromyalgia patients. Seventeen patients were randomly assigned to the SMR training (n = 9) or to a sham protocol (n = 8). All participants were trained during 6 sessions, and fMRI and EEG power elicited by synchronization and desynchronization trials were analyzed. In the SMR training group, four patients achieved the objective of SMR modulation in more than 70% of the trials from the second training session (good responders), while five patients performed the task at the chance level (bad responders). Good responders to the neurofeedback training significantly reduced pain and increased both SMR power modulation and functional connectivity of motor and somatosensory related areas during the last neurofeedback training session, whereas no changes in brain activity or pain were observed in bad responders or participants in the sham group. In addition, we observed that good responders were characterized by reduced impact of fibromyalgia and pain symptoms, as well as by increased levels of health-related quality of life during the pre-training sessions. In summary, the present study revealed that neurofeedback training of SMR elicited significant brain changes in somatomotor areas leading to a significant reduction of pain in fibromyalgia patients. In this sense, our research provide evidence that neurofeedback training is a promising tool for a better understanding of brain mechanisms involved in pain chronification.

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Section: Discussionmentioning

confidence: 60%

Self-Regulation of SMR Power Led to an Enhancement of Functional Connectivity of Somatomotor Cortices in Fibromyalgia Patients

et al. 2020

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“…Qualitative similarities in patterns of connectivity alterations in healthy volunteers and chronic pain patients need not necessarily stem from the same underlying mechanisms. For example, insula activity has been related to multiple pain mechanisms, from elaboration of a noxious peripheral drive in healthy participants (Peltz et al, 2011), to modulation and chronification of pain in chronic pain patients (Lu et al, 2016). We suggest that a multi-modal approach (perhaps including MRI data, behavioural and autonomic nervous system information) might offer improved characterisation of individual pain mechanisms, in turn facilitating meaningful comparisons between differing pain phenotypes.…”

Section: Discussionmentioning

confidence: 96%

Sustained perturbation in functional connectivity induced by cold pain

Makovac

Dipasquale

Jackson

et al. 2020

European Journal of Pain

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Background Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic‐pain related comorbidities, such as anxiety and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain‐free individuals, remains unknown. Method In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale. Results We saw DMN FC changes during painful stimulation and that inter‐network connectivity between the rAI with the vmPFC increased during pain, whereas PAG‐precuneus FC decreased. Pain‐induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals' subjectively reported pain. Conclusions We demonstrate FC changes during and following tonic cold‐pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive. Significance How pain‐related resting state networks are affected by tonic cold‐pain remains unknown. We investigated functional connectivity alterations during and following tonic cold pain in healthy volunteers. Cold pain perturbed the functional connectivity of the ventro‐medial prefrontal cortex, anterior insula, and the periacquaductal grey area. These connectivity changes were associated with the magnitude of individuals’ reported pain. We suggest that some connectivity changes described in chronic pain patients may be due to an ongoing afferent peripheral drive.

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“…Therefore, NP management may be involved in the complex connections associated with the key node of pain network rather than simply structural changes [10]. of NP [11,12]. There exists the D1 and D2 dopamine receptors in the insula [13,14], which participates in the modulation of chronic nociception [15,16].…”

Section: Introductionmentioning

confidence: 99%

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

Chen

et al. 2020

Neural Plasticity

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Objective. To investigate the reorganization of insular subregions in individuals suffering from neuropathic pain (NP) after incomplete spinal cord injury (ISCI) and further to disclose the underlying mechanism of NP. Method. The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all individuals were obtained using a 3.0 Tesla MRI system. A comparative analysis of structure and function connectivity (FC) with insular subareas as seeds in 10 ISCI individuals with below-level NP (ISCI-P), 11 ISCI individuals without NP (ISCI-N), and 25 healthy controls (HCs) was conducted. Associations between the structural and functional alteration of insula subregions and visual analog scale (VAS) scores were analyzed using the Pearson correlation in SPSS 20. Results. Compared with ISCI-N patients, when the left posterior insula as the seed, ISCI-P showed increased FC in right cerebellum VIIb and cerebellum VIII, Brodmann 37 (BA 37). When the left ventral anterior insula as the seed, ISCI-P indicated enhanced FC in right BA18 compared with ISCI-N patients. These increased FCs positively correlated with VAS scores. Relative to HCs, ISCI-P presented increased FC in the left hippocampus when the left dorsal anterior insula was determined as the seed. There was no statistical difference in the volume of insula subregions among the three groups. Conclusion. Our study indicated that distinctive patterns of FC in each subregion of insula suggest that the insular subareas participate in the NP processing through different FC following ISCI. Further, insula subregions could serve as a therapeutic target for NP following ISCI.

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Insular Cortex is Critical for the Perception, Modulation, and Chronification of Pain

Cited by 212 publications

References 99 publications

Self-Regulation of SMR Power Led to an Enhancement of Functional Connectivity of Somatomotor Cortices in Fibromyalgia Patients

Self-Regulation of SMR Power Led to an Enhancement of Functional Connectivity of Somatomotor Cortices in Fibromyalgia Patients

Sustained perturbation in functional connectivity induced by cold pain

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

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