Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex.

Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitary-adrenal axis stimulation. Instead of consecutive hypothalamus-pituitary-adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism. This neurogenic effect was more pronounced after high-thoracic level (Th1) SCI disconnecting adrenal gland innervation, compared with low-thoracic level (Th9) SCI. Prophylactic adrenalectomy completely prevented SCI-induced glucocorticoid excess and lymphocyte depletion but did not prevent pneumonia. When adrenalectomized mice were transplanted with denervated adrenal glands to restore physiologic glucocorticoid levels, the animals were completely protected from pneumonia. These findings identify a maladaptive sympathetic-neuroendocrine adrenal reflex mediating immunosuppression after SCI, implying that therapeutic normalization of the glucocorticoid and catecholamine imbalance in SCI patients could be a strategy to prevent detrimental infections.

Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

Dissociation of motor task-induced cortical excitability and pain perception changes in healthy volunteers.

BACKGROUND: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. CONCLUSIONS/SIGNIFICANCE: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training.