fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children

Complex regional pain syndrome (CRPS) in paediatric patients is clinically distinct from the adult condition in which there is often complete resolution of its signs and symptoms within several months to a few years. The ability to compare the symptomatic and asymptomatic condition in the same individuals makes this population interesting for the investigation of mechanisms underlying pain and other symptoms of CRPS. We used fMRI to evaluate CNS activation in paediatric patients (9-18 years) with CRPS affecting the lower extremity. Each patient underwent two scanning sessions: once during an active period of pain (CRPS(+)), and once after symptomatic recovery (CRPS(-)). In each session, mechanical (brush) and thermal (cold) stimuli were applied to the affected region of the involved limb and the corresponding mirror region of the unaffected limb. Two fundamental fMRI analyses were performed: (i) within-group analysis for CRPS(+) state and CRPS(-) state for brush and cold for the affected and unaffected limbs in each case; (ii) between-group (contrast) analysis for activations in affected and unaffected limbs in CRPS or post-CRPS states. We found: (i) in the CRPS(+) state, stimuli that evoked mechanical or cold allodynia produced patterns of CNS activation similar to those reported in adult CRPS; (ii) in the CRPS(+) state, stimuli that evoked mechanical or cold allodynia produced significant decreases in BOLD signal, suggesting pain-induced activation of endogenous pain modulatory systems; (iii) cold- or brush-induced activations in regions such as the basal ganglia and parietal lobe may explain some CNS-related symptoms in CRPS, including movement disorders and hemineglect/inattention; (iv) in the CRPS(-) state, significant activation differences persisted despite nearly complete elimination of evoked pain; (v) although non-noxious stimuli to the unaffected limb were perceived as equivalent in CRPS(+) and CRPS(-) states, the same stimulus produced different patterns of activation in the two states, suggesting that the 'CRPS brain' responds differently to normal stimuli applied to unaffected regions. Our results suggest significant changes in CNS circuitry in patients with CRPS.