The somatosensory link: S1 functional connectivity is altered by sustained pain and associated with clinical/autonomic dysfunction in fibromyalgia

Chronic pain patients feel pain as a primarily somatosensory sensation, although it is well understood that clinical pain is much more than somatic and encompasses multiple affective and cognitive domains. Fibromyalgia (FM) is a prototypical functional pain syndrome characterized by multi-dimensional symptomatology. Symptoms include widespread pain, mood disturbance with significant pain catastrophizing, cognitive and physical fatigue, dysfunction of autonomic activity, and amplified sensitivity and temporal summation to experimental pain stimuli (1).Multiple neuroimaging studies have supported the theory that FM is primarily a multi-system disorder of central nervous system (e.g. brain) processing. However, the precise linkage between the circuitries processing somatic sensation with those underlying broader affective and cognitive domains remains unknown. Functional connectivity magnetic resonance imaging (fcMRI) is an adaptation of fMRI that may help assess brain circuitry supporting spontaneous clinical pain. While spontaneous clinical pain(2), and negative affect (3) components of FM have been linked to altered resting (or intrinsic)functional brain connectivity, previous studies have not systematically probed the primary somatosensory cortex (S1) – a potentially integral brain area for somatic symptomatology such as pain. In FM, decreased secondary somatosensory (S2) connectivity to primary motor cortex (3), and reduced connectivity between S2 and S1 (4) were also recently reported. Interestingly, S1 connectivity is also sensitive to sustained experimental pain stimulation in healthy adults (5), suggesting malleable state-like properties for S1 connectivity networks. This view is consistent with generalized reports that functional brain connectivity can reflect both state and trait processes (6). Such state processes may even underlie the hyperalgesia, allodynia, and temporal summation commonly noted in chronic pain patients, as region-specific changes in S1 connectivity may support maladaptive changes in central processing of somatosensory afference. Our current study investigated evoked-pain state induced alterations in S1 connectivity in chronic pain patients suffering from FM. We also explored how altered S1 connectivity is associated with clinically-relevant variables such as pain intensity and pain-related catastrophizing, key determinants of FM morbidity. Furthermore, we linked evoked deep-tissue pain modulated S1 connectivity with temporal summation of pain and core non-somatic aspects of FM pathophysiology including altered autonomic modulation. The latter investigation follows past studies that have noted autonomic dysfunction in FM patients (7), linking such dysfunction with clinically-relevant parameters (7, 8). We hypothesized that multi-system pathology, common to FM, is supported by altered functional S1 connectivity at rest and/or in response to evoked nociceptive stimuli highly relevant to FM patients – i.e. deep-tissue pain.