Consequences of spinal cord injury on the sympathetic nervous system

Abstract

Spinal cord injury (SCI) damages multiple structures at the lesion site, including ascending, descending, and propriospinal axons; interrupting the conduction of information up and down the spinal cord. Additionally, axons associated with the autonomic nervous system that control involuntary physiological functions course through the spinal cord. Moreover, sympathetic, and parasympathetic preganglionic neurons reside in the spinal cord. Thus, depending on the level of an SCI, autonomic function can be greatly impacted by the trauma resulting in dysfunction of various organs. For example, SCI can lead to dysregulation of a variety of organs, such as the pineal gland, the heart and vasculature, lungs, spleen, kidneys, and bladder. Indeed, it is becoming more apparent that many disorders that negatively affect quality-of-life for SCI individuals have a basis in dysregulation of the sympathetic nervous system. Here, we will review how SCI impacts the sympathetic nervous system and how that negatively impacts target organs that receive sympathetic innervation. A deeper understanding of this may offer potential therapeutic insight into how to improve health and quality-of-life for those living with SCI.

Keywords: dysregulation; preganglionic neurons; spinal cord injury; sympathetic innervation; sympathetic nervous system; therapeutics.

FIGURE 1

A schematic of the sympathetic and parasympathetic innervation to peripheral organs. Sympathetic preganglionic neurons reside in the intermediolateral cell column in the thoracolumbar spinal cord and project out to and synapse upon sympathetic postganglionic neurons within the sympathetic chain. The sympathetic postganglionic neurons innervate target organs in the periphery. For the parasympathetic system, preganglionic neurons residing in the brainstem and sacral spinal cord send projections directly to target organs in the periphery. (Created using www.biorender.com).

FIGURE 2

Overview of the spinal sympathetic circuit. When there is a stimuli below the level of injury such as colon distension in the above example, primary afferent fibers from that organ travel into the spinal cord and synapse onto propriospinal interneurons located near the central canal. From here, propriospinal interneurons travel rostrally across many spinal segments to synapse upon either (1) sympathetic preganglionic neurons located in the intermediolateral cell column, or (2) interneurons located near sympathetic preganglionic neurons. Sympathetic preganglionic neurons project out to the sympathetic chain to synapse onto sympathetic postganglionic neurons that innervate target organs in the periphery. (Created using www.biorender.com).

FIGURE 3

Autonomic control of the cardiovascular system and how SCI impacts the cardiovascular system. (A) The heart is innervated by sympathetic postganglionic neurons that receive input from sympathetic preganglionic neurons in thoracic segments 1–4. Parasympathetic regulation of the heart originates from the nucleus ambiguous and dorsal motor nucleus of vagus within the brainstem. Autonomic control over the vasculature is solely from the sympathetic nervous system. (B) SCI at or above T6 results in deranged sympathetic activity that results in orthostatic hypotension, bradycardia in the acute phase, and autonomic dysreflexia. (Created using www.biorender.com).

FIGURE 4

Autonomic control of the visual system and how SCI impacts the visual system. (A) Sympathetic preganglionic neurons in upper thoracic spinal segments extend out of the spinal cord via the ventral horn to synapse upon sympathetic postganglionic neurons in the superior cervical ganglion. These neurons then directly innervate the levator palpebrae superioris muscle within the upper eyelid, the lacrimal glands, and the medial and lateral rectus muscles. (B) SCI may result in Horner’s syndrome where the upper eyelid begins to droop. Similarly, SCI may cause the lacrimal glands to have reduced tear production and atrophy that can ultimately result in dry eye. (Created using www.biorender.com).

FIGURE 5

Autonomic control of the pupillary light reflex and how SCI impacts it. (A) When the retina detects a dim light, it sends a stimulus to the brain via the optic nerve. This signal, in turn, results in the activation of sympathetic preganglionic neurons in the upper thoracic spinal cord that synapse onto sympathetic postganglionic neurons within the superior cervical ganglion. Some of these sympathetic postganglionic neurons innervate the dilatory pupillae muscle (pink). Release of norepinephrine from the sympathetic postganglionic neuron terminals cause the pupil to dilate to allow more light to reach the retina. Alternatively, perception of a bright light by the eye results in the activation of the parasympathetic nervous system. Parasympathetic neurons within Edinger–Westphal nucleus of the midbrain extend their axons out via the oculomotor nerve to synapse onto parasympathetic postganglionic neurons within the ciliary ganglion. These postganglionic neurons innervate the sphincter pupillae muscle (yellow) to cause the pupil to constrict, limiting the amount of light reaching the retina. (B) SCI causes irregular dilation of pupils resulting in uneven pupil size, a condition known as anisocoria, and Adie’s Tonic Pupil where the pupil does not properly respond to light. (Created using www.biorender.com).

FIGURE 6

Neuronal control of the lower urinary tract (LUT). The lower urinary tract receives neuronal control from both branches of the autonomic nervous system and the somatic nervous system. Sympathetic control arises from sympathetic preganglionic neurons in thoracic segments 11 to lumbar segment 2 that extend axons out the hypogastric nerve and synapse onto sympathetic postganglionic neurons within the inferior mesenteric ganglion. These sympathetic postganglionic neurons innervate the bladder, IUS, and urethra. Parasympathetic preganglionic neurons in sacral spinal cord segments 2–4 project axons out of the cord via the pelvic nerve and synapse onto parasympathetic postganglionic neurons within the pelvic ganglion. These postganglionic neurons directly innervate the bladder, IUS, and urethra. Interestingly, the external urethral sphincter is the only muscle in the LUT that is controlled via the somatic nervous system. This allows for voluntary control over urinary functions. (Created using www.biorender.com).

FIGURE 7

Spinal cord injury results in lower urinary tract (LUT) dysfunction. (A) An upper motor neuron injury is when there is no direct damage of the neurons that innervate the bladder, leaving the spinal reflex pathway intact. An upper motor neuron injury results in a reflexive or spastic bladder and detrusor-sphincter dyssynergia (DSD), where the detrusor and sphincter muscles abnormally contract simultaneously, resulting in inefficient voiding. (B) Lower motor neuron injury results in damage to the neurons that directly innervate the bladder. A lower motor neuron injury produces an areflexic or flaccid bladder where the detrusor muscle does not contract. This results in retention of urine in the bladder that makes the bladder become over-stretched. (Created using www.biorender.com).