Passive Hind-Limb Cycling Reduces the Severity of Autonomic Dysreflexia After Experimental Spinal Cord Injury

Abstract

Background. Spinal cord injury (SCI) induces alterations in cardio-autonomic control of which autonomic dysreflexia (AD), a condition characterized by life-threatening hypertension, is arguably the most insidious. Passive hind-limb cycling represents a low-cost therapeutic intervention with demonstrable cardiovascular, sensory, and motor benefits. Objective. To investigate the effect of passive hind-limb cycling on AD in rodents with T3 SCI. Methods. Forty-five male Wistar rats were evenly assigned to either uninjured control (CON), SCI, or SCI plus hind-limb cycling exercise (SCI-EX). At the end of the experimental period (day 32), rats were randomly assigned to stream 1 (n = 24) or stream 2 (n = 21). Stream 1 rats were assessed for AD severity (pressor response to colorectal distension) and were then perfused for tissue dissection and immunohistochemistry. Stream 2 rats underwent excision of the superior mesenteric artery for in vitro myography assessments. Results. From 2 weeks post-SCI onwards, SCI-EX rats exhibited a significant reduction in the pressor response to colorectal distension versus SCI (P < .001). Reduced AD severity in SCI-EX rats was accompanied by a prevention of the SCI-induced increase in density of CGRP+ afferents in the dorsal horn (P = .001). Conversely, both SCI and SCI-EX rats exhibited a similar degree of mesenteric endothelial dysfunction and α-adrenoceptor hypersensitivity versus CON. Conclusion. Passive hind-limb cycling reduces the severity of AD in SCI, and is correlated with changes in primary afferent morphology, but has limited effects on the peripheral vasculature.