Abstract
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. 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. 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. 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. 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.
Highlights
Resting state functional magnetic resonance imaging is a useful tool for investigating acute and chronic pain
We focused our interest in ventromedial prefrontal cortex (vmPFC) as the central hub of the DMN, rostral anterior insula (rAI) as the central hub of the SN and often involved in chronic pain syndromes(Cottam et al, 2018), and the sub-genual anterior cingulate cortex (ACC) and periaqueductal grey (PAG) (both central hubs in the descending pain modulation pathway(Yu et al, 2014))
The effects of ongoing cold pain elicited alterations in the default mode, salience, central executive and descending pain control networks, several of which persisted for several minutes following stimulation
Summary
Resting state functional magnetic resonance imaging (rs-fMRI) is a useful tool for investigating acute and chronic pain. Healthy volunteer studies facilitate examining pain mechanisms independently of these differences, but surprisingly, rs-fMRI studies evaluating tonic painful stimulation in these individuals remain relatively scarce. Reports of experimentally-induced tonic muscle pain(Alshelh et al, 2018) produced decreased oscillatory power in the main DMN hubs (posterior cingulate cortexPCC, inferior parietal cortex, and vmPFC) and a pilot study of pain-inducing intramuscular hypertonic saline injection described insula-DMN connectivity changes (Zhang et al, 2014). The effects of experimentally-induced noxious tonic stimulation in healthy volunteers on other pain-related functional networks, for example, endogenous pain control, or how networks interact with one another, remains to be assessed. FC changes observed in chronic pain may reflect the upstream effects of ongoing afferent peripheral nociceptive drive; in this study we investigated this using tonic cold pain in pain-free healthy volunteers
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