Sustained perturbation in functional connectivity induced by cold pain.

Area of Science:

• Neuroscience
• Pain Research
• Functional Neuroimaging

Background:

• Chronic pain is associated with functional connectivity (FC) alterations, but comorbidities like anxiety and depression complicate findings.
• Healthy volunteer studies are crucial for isolating the effects of noxious stimulation on FC, independent of psychological sequelae.
• Previous research noted connectivity changes in task-negative (default mode network) and task-positive (salience network) networks, but effects on pain-control networks during tonic pain were unknown.

Purpose of the Study:

• To investigate functional connectivity (FC) alterations in healthy, pain-free individuals during and after tonic cold pain.
• To examine how tonic noxious stimulation affects key brain regions involved in pain processing and descending pain control.
• To determine if FC changes are related to the subjective intensity of pain.

Main Methods:

• Twenty healthy volunteers underwent functional connectivity (FC) assessment using fMRI.
• FC was measured before, during, and after tonic cold painful stimulation.
• Brain regions of interest included the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC), and periaqueductal grey (PAG).
• Subjective pain intensity was recorded using a computerized visual analogue scale.

Main Results:

• Tonic cold pain induced significant changes in default mode network (DMN) functional connectivity.
• Inter-network connectivity increased between the rostral anterior insula (rAI) and ventromedial prefrontal cortex (vmPFC) during pain.
• Connectivity between the periaqueductal grey (PAG) and precuneus decreased during painful stimulation.
• Pain-induced FC alterations persisted after the noxious stimulus was removed.
• Observed FC changes were positively correlated with the magnitude of subjectively reported pain.

Conclusions:

• Tonic cold pain significantly alters functional connectivity (FC) in healthy participants, both during and after stimulation.
• Persistent FC changes suggest that ongoing nociceptive input may contribute to brain network alterations.
• Similarities between these findings and FC changes in chronic pain patients imply that afferent nociceptive drive could be a common underlying factor.