Dan-Mikael Ellingsen

Pain catastrophizing is prominent in chronic pain conditions such as fibromyalgia and has been proposed to contribute to the development of pain widespreadness. However, the brain mechanisms responsible for this association are unknown. We hypothesized that increased resting salience network (SLN) connectivity to nodes of the default mode network (DMN), representing previously reported pain-linked cross-network enmeshment, would be associated with increased pain catastrophizing and widespreadness across body sites. We applied functional magnetic resonance imaging (fMRI) and digital pain drawings (free-hand drawing over a body outline, analyzed using conventional software for multivoxel fMRI analysis) to investigate precisely quantified measures of pain widespreadness and the associations between pain catastrophizing (Pain Catastrophizing Scale), resting brain network connectivity (Dual-regression Independent Component Analysis, 6-minute multiband accelerated fMRI), and pain widespreadness in fibromyalgia patients (N = 79). Fibromyalgia patients reported pain in multiple body areas (most frequently the spinal region, from the lower back to the neck), with moderately high pain widespreadness (mean ± SD: 26.1 ± 24.1% of total body area), and high pain catastrophizing scale scores (27.0 ± 21.9, scale range: 0-52), which were positively correlated (r = 0.26, P = 0.02). A whole-brain regression analysis focused on SLN connectivity indicated that pain widespreadness was also positively associated with SLN connectivity to the posterior cingulate cortex, a key node of the DMN. Moreover, we found that SLN-posterior cingulate cortex connectivity statistically mediated the association between pain catastrophizing and pain widespreadness (P = 0.01). In conclusion, we identified a putative brain mechanism underpinning the association between greater pain catastrophizing and a larger spatial extent of body pain in fibromyalgia, implicating a role for brain SLN-DMN cross-network enmeshment in mediating this association.

The patient-clinician interaction can powerfully shape treatment outcomes such as pain, but is often considered an intangible “art-of-medicine”, and has largely eluded scientific inquiry. Although brain correlates of social processes such as empathy and theory-of-mind have been studied using single-subject designs, the specific behavioral and neural mechanisms underpinning the patient-clinician interaction are unknown. Using a two-person interactive design, we simultaneously recorded functional MRI (i.e. hyperscanning) in patient-clinician dyads, who interacted via live video while clinicians treated evoked pain in chronic pain patients. Our results show that patient analgesia is mediated by patient-clinician nonverbal behavioral mirroring and brain-to-brain concordance in circuitry implicated in theory-of-mind and social mirroring. Dyad-based analyses showed extensive dynamic coupling of these brain nodes with the partners’ brain activity, yet only in dyads where clinical rapport had been established prior to the interaction. These findings point to a putatively key brain-behavioral mechanism for therapeutic alliance and psychosocial analgesia.