Sustained deep-tissue pain alters functional brain connectivity

Abstract

Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically-relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, fronto-parietal control and default mode networks; SMN, SLN, DAN, FCN and DMN) was evaluated with functional-connectivity MRI, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable with no significant changes of subjects’ pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala, was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to inter-individual differences in pain sensitivity.

Motion sickness increases functional connectivity between visual motion and nausea-associated brain regions

“…when an area is activated by a stimulus, during sustained stimulation that region reduces its connectivity to areas it is typically connected to at rest. This phenomenon has been found for sustained auditory/cognitive [23], working memory [24], and pain [25, 26] stimuli. Additionally, connectivity between activated regions and brain areas outside that region's intrinsic network, may be upregulated during sustained stimulation.…”

The Lateral Prefrontal Cortex Mediates the Hyperalgesic Effects of Negative Cognitions in Chronic Pain Patients

“…CPA is a technique that has been successfully adopted in psychophysical investigations 7, 32-35 , including in FM patients 17 , and in neuroimaging studies we recently conducted 18, 22 . Among the advantages of CPA over other more commonly used methods of pain stimulation (e.g., contact heat), CPA stimuli have a preferential effect on deep tissue nociceptors, such as in muscles 34 , and thus may better mimic clinical pain 38 , particularly in conditions characterized by myofascial tenderness, such as FM.…”

White Matter Involvement in Chronic Musculoskeletal Pain

“…There is extensive evidence that abnormalities exist in the brains of chronic musculoskeletal pain patients in gray matter (GM) volume/thickness 13,15,27,40,44,49,57,61 , GM density 7,9,60,62,64,65 , and both acute pain-related 16,19 and resting state 8,28,38,43 functional activity. While some work has been published regarding the relationship between chronic pain disorders and neural white matter (WM) 12,18,21,25,26,44,45,50,72,73 , only one study 50 has used contemporary analysis approaches to compare measures of anisotropy and diffusion specifically within between chronic musculoskeletal pain patients with temporomandibular disorder (TMD) and healthy volunteers.…”