Intraspinal Plasticity Associated With the Development of Autonomic Dysreflexia After Complete Spinal Cord Injury

Abstract

Traumatic spinal cord injury (SCI) leads to disruption of sensory, motor and autonomic function, and triggers structural, physiological and biochemical changes that cause reorganization of existing circuits that affect functional recovery. Propriospinal neurons (PN) appear to be very plastic within the inhibitory microenvironment of the injured spinal cord by forming compensatory circuits that aid in relaying information across the lesion site and, thus, are being investigated for their potential to promote locomotor recovery after experimental SCI. Yet the role of PN plasticity in autonomic dysfunction is not well characterized, notably, the disruption of supraspinal modulatory signals to spinal sympathetic neurons after SCI at the sixth thoracic spinal segment or above resulting in autonomic dysreflexia (AD). This condition is characterized by unmodulated sympathetic reflexes triggering sporadic hypertension associated with baroreflex mediated bradycardia in response to noxious yet unperceived stimuli below the injury to reduce blood pressure. AD is frequently triggered by pelvic visceral distension (bowel and bladder), and there are documented structural relationships between injury-induced sprouting of pelvic visceral afferent C-fibers. Their excitation of lumbosacral PN, in turn, sprout and relay noxious visceral sensory stimuli to rostral disinhibited thoracic sympathetic preganglionic neurons (SPN) that manifest hypertension. Herein, we review evidence for maladaptive plasticity of PN in neural circuits mediating heightened sympathetic reflexes after complete high thoracic SCI that manifest cardiovascular dysfunction, as well as contemporary research methodologies being employed to unveil the precise contribution of PN plasticity to the pathophysiology underlying AD development.

Keywords: cardiovascular dysfunction; hypertension; interneuron; propriospinal; sympathetic preganglionic neurons.

Figure 1

Schematic representation of neuronal pathways disrupted/rerouted by complete spinal cord injury (SCI) above the sixth thoracic (T6) spinal level associated with the development of autonomic dysreflexia (AD) evoked by noxious pelvic visceral distension. Sensory afferent fibers (blue) from the distended bladder or colon transmit noxious stimuli to short and/or long projection propriospinal neurons (PN; green) present in the dorsal gray commissure (DGC) at corresponding spinal levels. These PN then relay the signal rostrally to activate sympathetic preganglionic neurons (SPN) present in the thoracolumbar intermediolateral cell column (IML) directly or via interneurons to trigger adrenal hyperactivity, peripheral vasoconstriction, and consequent hypertension. The change in pressure is sensed by baroreceptors (black dots) in the aortic arch which relay the information via the nucleus tractus solitarius (NTS) in the medulla to the nucleus ambiguous (NA) that elicits: (1) a parasympathetic bradycardic response and/or; (2) concomitant neuromodulation via caudal and rostral ventrolateral medulla (CVLM and RVLM) projections to the IML directly or via interneurons to maintain normal blood pressure. After T6 SCI, the decentralized SPN elicits uninhibited vasoconstriction and hypertension, while the NA signals baroreflex mediated bradycardia. The lack of supraspinal regulation of SPN below the injury site maintains the hypertensive response until the noxious stimuli are removed, and maladaptive plasticity of both primary afferent fibers and PN are associated with the development of AD.