Neuropathic pain relief and altered brain networks after dorsal root entry zone microcoagulation in patients with spinal cord injury.

Spinal cord injury (SCI) below-level neuropathic pain is a difficult condition to treat both pharmacologically and surgically. Successful treatment using surgically created lesions of the spinal cord dorsal root entry zone (DREZ), guided by intramedullary monitoring of neuronal electrical hyperactivity, has shown that DREZs both cephalad and caudal to the level of injury can be the primary generators of SCI below-level pain. Below-level pain perception follows a unique somatotopic map of DREZ pain generators, and neuronal transmission to brain pain centres can occur primarily through sympathetic nervous system (SNS) pathways. This study evaluated changes in brain resting-state and task-based functional magnetic resonance imaging responses before and after neuroelectrically guided DREZ microcoagulation surgery. Eight persons with clinically complete SCI who suffered chronic, severe and unrelenting below-level neuropathic pain refractory to all pharmacological management were investigated before and after the surgical intervention. Baseline differences between DREZ subjects, group-matched low pain SCI and healthy controls were observed in medial primary somatosensory and motor cortex connectivity to the hippocampus, amygdala and medial prefrontal cortex. The DREZ surgery led to short-term (12 days) almost complete pain relief in all participants and long-term (1+ year) pain relief in all participants receiving DREZ lesioning both cephalad and caudal to the level of injury (six out of eight participants). Follow-up 12 days post-operatively indicated that DREZ surgery normalized prior negative functional coupling between primary sensory (S1) and motor (M1) cortices to the hippocampus, amygdala and the medial prefrontal cortex, increased M1 to putamen and amygdala connectivity and decreased limbic to cerebellar connectivity. DREZ hyperactivity was found both cephalad and caudal to the level of injury. The regional distribution of hyperactive regions corresponded not to classical dermatomes but rather mapped on to intermediolateral (IML) cell column end organ innervation of body regions of below-level pain perception, consistent with a non-classical SNS-mediated somatotopic map of DREZ below-level pain generators. The results indicate that neuroelectrically guided DREZ microcoagulation alters a medial prefrontal-somatosensory-limbic network that is separate from classical pain pathways. This provides further evidence that below-level SCI pain originates in hyperactive DREZs and can be relayed to the brain via the SNS.