Somatotopic disruption of the functional connectivity of the primary sensorimotor cortex in complex regional pain syndrome type 1

Abstract

In complex regional pain syndrome (CRPS), the representation area of the affected limb in the primary sensorimotor cortex (SM1) reacts abnormally during sensory stimulation and motor actions. We recorded 3T functional magnetic resonance imaging resting‐state data from 17 upper‐limb CRPS type 1 patients and 19 healthy control subjects to identify alterations of patients' SM1 function during spontaneous pain and to find out how the spatial distribution of these alterations were related to peripheral symptoms. Seed‐based correlations and independent component analyses indicated that patients' upper‐limb SM1 representation areas display (i) reduced interhemispheric connectivity, associated with the combined effect of intensity and spatial extent of limb pain, (ii) increased connectivity with the right anterior insula that positively correlated with the duration of CRPS, (iii) increased connectivity with periaqueductal gray matter, and (iv) disengagement from the other parts of the SM1 network. These findings, now reported for the first time in CRPS, parallel the alterations found in patients suffering from other chronic pain conditions or from limb denervation; they also agree with findings in healthy persons who are exposed to experimental pain or have used their limbs asymmetrically. Our results suggest that CRPS is associated with a sustained and somatotopically specific alteration of SM1 function, that has correspondence to the spatial distribution of the peripheral manifestations and to the duration of the syndrome.

A Case of a Father and Son With Complex Regional Pain Syndrome Type 1 Exhibiting Different Resting-State Functional Connectivity on Functional MRI

“…Prior research has identified abnormalities in rsFC within multiple brain networks in patients with CRPS. These networks include the fronto-parietal [ 4 , 6 ], motor [ 3 , 7 , 10 ], somatosensory [ 5 , 6 , 11 ], subcortical [ 3 , 6 , 10 , 11 ], salience [ 4 , 8 , 9 ], central executive [ 4 ], and default mode [ 4 , 5 ] networks. These brain network alterations can be classified into two broad categories.…”

“…These brain network alterations can be classified into two broad categories. The first category includes abnormalities in pain sensation [3][4][5][6][7][8][9]11] and cognitive-emotional changes [6,8]. The second involves limb movement disorders such as dystonia [3,4,10].…”

“…Complex regional pain syndrome (CRPS) is a chronic pain syndrome that develops following fractures, soft tissue damage, or surgery and is characterized by pain, swelling, limited range of joint motion, vasomotor instability, skin changes, and patchy osteoporosis [1,2]. Although the pathogenesis is uncertain, classic and neurogenic inflammation in the affected limb's peripheral tissues and central nervous system pathophysiology, such as changes in nociceptive perception, contribute to its occurrence [1,2] Resting-state functional connectivity (rsFC) changes observed on functional magnetic resonance imaging (fMRI) have been recently investigated as indicators of central nervous system abnormalities in patients with CRPS [3][4][5][6][7][8][9][10][11]. Advanced research has identified various rsFC anomalies that are associated with alterations in pain perception and cognitive processes [3][4][5][6][7][8][9]11].…”

“…Although the pathogenesis is uncertain, classic and neurogenic inflammation in the affected limb's peripheral tissues and central nervous system pathophysiology, such as changes in nociceptive perception, contribute to its occurrence [1,2] Resting-state functional connectivity (rsFC) changes observed on functional magnetic resonance imaging (fMRI) have been recently investigated as indicators of central nervous system abnormalities in patients with CRPS [3][4][5][6][7][8][9][10][11]. Advanced research has identified various rsFC anomalies that are associated with alterations in pain perception and cognitive processes [3][4][5][6][7][8][9]11]. Some of these anomalies are also related to motor function disturbances [3,4,10].…”