Diversity of sympathetic vasoconstrictor pathways and their plasticity after spinal cord injury

Abstract

Sympathetic vasoconstrictor pathways pass through paravertebral ganglia carrying ongoing and reflex activity arising within the central nervous system to their vascular targets. The pattern of reflex activity is selective for particular vascular beds and appropriate for the physiological outcome (vasoconstriction or vasodilation). The preganglionic signals are distributed to most postganglionic neurones in ganglia via synapses that are always suprathreshold for action potential initiation (like skeletal neuromuscular junctions). Most postganglionic neurones receive only one of these "strong" inputs, other preganglionic connections being ineffective. Pre- and postganglionic neurones discharge normally at frequencies of 0.5-1 Hz and maximally in short bursts at <10 Hz. Animal experiments have revealed unexpected changes in these pathways following spinal cord injury. (1) After destruction of preganglionic neurones or axons, surviving terminals in ganglia sprout and rapidly re-establish strong connections, probably even to inappropriate postganglionic neurones. This could explain aberrant reflexes after spinal cord injury. (2) Cutaneous (tail) and splanchnic (mesenteric) arteries taken from below a spinal transection show dramatically enhanced responses in vitro to norepinephrine released from perivascular nerves. However the mechanisms that are modified differ between the two vessels, being mostly postjunctional in the tail artery and mostly prejunctional in the mesenteric artery. The changes are mimicked when postganglionic neurones are silenced by removal of their preganglionic input. Whether or not other arteries are also hyperresponsive to reflex activation, these observations suggest that the greatest contribution to raised peripheral resistance in autonomic dysreflexia follows the modifications of neurovascular transmission.

Fig. 1

Extracellular recording of multiunit sympathetic activity in skin and muscle nerves of conscious humans. (A) from intact individual; (B) from a subject with complete spinal cord transection at C6. At arrows, the skin over the forearm was stimulated electrically. Note the absence of ongoing activity in both nerves and the synchronous activation by the stimulus after spinal cord injury. Modified from Stjernberg et al. (1986)

Fig. 2

Contractile responses of segments of (A) cutaneous (tail) artery and (B) splanchnic (mesenteric) artery isolated from (above) control rats and (below) rats 7–8 weeks after spinal transection at (A) T8 and (B) T4. Trains of the same number of transmural electrical stimuli at different frequencies (indicated by bars at bottom) were presented to each vessel to activate the sympathetic postganglionic terminals. Responses in vessels from spinalized rats were greatly enhanced compared with controls. Redrawn from (A) Yeoh et al. (2004a) and (B) Brock et al. (2006)

Fig. 3

Diagram showing sites of lesions used to study long term effects on neurovascular transmission in arterial vessels of rats. (1) Transection of thoracic spinal cord without damage to preganglionic neurones. (2) Transection of paravertebral chain to remove preganglionic inputs (decentralization). (3) Transection of postganglionic nerves to denervate artery. Segments of artery were removed from the animals after 2–8 weeks and contractile responses to stimulation of perivascular sympathetic nerves were recorded during exposure to adrenoceptor antagonists and other drugs. that selectively interfere with neurovascular mechanisms