Resting state functional connectivity differentiation of neuropathic and nociceptive pain in individuals with chronic spinal cord injury.

Many individuals with spinal cord injury live with debilitating chronic pain that may be neuropathic, nociceptive, or a combination of both in nature. Identification of brain regions demonstrating altered connectivity associated with the type and severity of pain experience may elucidate underlying mechanisms, as well as treatment targets. Resting state and sensorimotor task-based magnetic resonance imaging data were collected in 37 individuals with chronic spinal cord injury. Seed-based correlations were utilized to identify resting state functional connectivity of regions with established roles in pain processing: the primary motor and somatosensory cortices, cingulate, insula, hippocampus, parahippocampal gyri, thalamus, amygdala, caudate, putamen, and periaqueductal gray matter. Resting state functional connectivity alterations and task-based activation associated with individuals' pain type and intensity ratings on the International Spinal Cord Injury Basic Pain Dataset (0-10 scale) were evaluated. We found that intralimbic and limbostriatal resting state connectivity alterations are uniquely associated with neuropathic pain severity, whereas thalamocortical and thalamolimbic connectivity alterations are associated specifically with nociceptive pain severity. The joint effect and contrast of both pain types were associated with altered limbocortical connectivity. No significant differences in task-based activation were identified. These findings suggest that the experience of pain in individuals with spinal cord injury may be associated with unique alterations in resting state functional connectivity dependent upon pain type.

Safety and feasibility of transcranial direct current stimulation stratified by corticospinal organization in children with hemiparesis.

Children with hemiparesis (CWH) due to stroke early in life face lifelong impairments in motor function. Transcranial direct current stimulation (tDCS) may be a safe and feasible adjuvant therapy to augment rehabilitation. Given the variability in outcomes following tDCS, tailored protocols of tDCS are required. We evaluated the safety, feasibility, and preliminary effects of a single session of targeted anodal tDCS based on individual corticospinal tract organization on corticospinal excitability. Fourteen CWH (age = 13.8 ± 3.63) were stratified into two corticospinal organization subgroups based on transcranial magnetic stimulation (TMS)-confirmed motor evoked potentials (MEP): ipsilesional MEP presence (MEPIL+) or absence (MEPIL-). Subgroups were randomized to real anodal or sham tDCS (1.5 mA, 20 min) applied to the ipsilesional (MEPIL + group) or contralesional (MEPIL- group) hemisphere combined with hand training. Safety was assessed with questionnaires and motor function evaluation, and corticospinal excitability was assessed at baseline and every 15 min for 1 h after tDCS. No serious adverse events occurred and anticipated minor side effects were reported and were self-limiting. Six of 14 participants had consistent ipsilesional MEPs (MEPIL + group). Paretic hand MEP amplitude increased in 5/8 participants who received real anodal tDCS to either the ipsilesional or contralesional hemisphere (+80% change). Application of tDCS based on individual corticospinal organization was safe and feasible with expected effects on excitability, indicating the potential for tailored tDCS protocols for CWH. Additional research involving expanded experimental designs is needed to confirm these effects and to determine if this approach can be translated into a clinically relevant intervention.

miR-338-5p Levels and Cigarette Smoking are Associated With Neuropathic Pain Severity in Individuals With Spinal Cord Injury: Preliminary Findings From a Genome-Wide microRNA Expression Profiling Screen.

OBJECTIVE: To identify microRNA biomarkers and clinical factors associated with neuropathic pain after spinal cord injury. DESIGN: Cross-sectional, secondary analysis of baseline data collected from ongoing clinical studies. Using a genome-wide microRNA screening approach, we studied differential microRNA expression in serum from 43 adults with spinal cord injury enrolled in ongoing clinical studies. Least squares regression was used to identify associations between microRNA expression, clinical factors, and neuropathic pain severity. SETTING: Community-dwelling individuals with spinal cord injury. PARTICIPANTS: Participants (N=43) were at least 18 years old with spinal cord injury, with 28 reporting neuropathic pain and 15 reporting no neuropathic pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pain presence, type, and intensity were assessed with the International Spinal Cord Injury Pain Basic Data Set. Serum microRNA normalized deep sequencing counts were quantified from blood samples. Participant demographic factors, injury characteristics, medication use, and health habits were collected via questionnaire. RESULTS: miR-338-5p expression and history of cigarette smoking were associated with and explained 37% of the variance in neuropathic pain severity (R2=0.37, F2,18=5.31, P=.02) independent of other clinical factors. No association was identified between miR-338-5p levels and nociceptive pain severity. CONCLUSIONS: Our findings suggest that miR-338-5p and cigarette smoking may both play a role in the development or maintenance of neuropathic pain after spinal cord injury. While additional work is needed to confirm these findings, validated target analysis suggests a neuroprotective role of miR-338-5p in modulating neuroinflammation and neuronal apoptosis and that its downregulation may result in maladaptive neuroplastic mechanisms contributing to neuropathic pain after spinal cord injury.

Motor Evoked Potentials as Potential Biomarkers of Early Atypical Corticospinal Tract Development in Infants with Perinatal Stroke.

Diagnosis of cerebral palsy (CP) after perinatal stroke is often delayed beyond infancy, a period of rapid neuromotor development with heightened potential for rehabilitation. This study sought to assess whether the presence or absence of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) could be an early biomarker of atypical development within the first year of life. In 10 infants with perinatal stroke, motor outcome was assessed with a standardized movement assessment. Single-pulse TMS was utilized to assess presence of MEPs. Younger infants (3-6 months CA, n = 5, 4/5 (80%)) were more likely to present with an MEP from the more-affected hemisphere (MAH) compared to older infants (7-12 months CA, n = 5, 0/5, (0%)) (p = 0.048). Atypical movement was demonstrated in the majority of infants with an absent MEP from the MAH (5/6, 83%) compared to those with a present MEP (1/4, 25%) (p = 0.191). We found that age influences the ability to elicit an MEP from the MAH, and motor outcome may be related to MAH MEP absence. Assessment of MEPs in conjunction with current practice of neuroimaging and motor assessments could promote early detection and intervention in infants at risk of CP.