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

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

Cold-activated raphé-spinal neurons in rats

In a search for sympathetic premotor neurons subserving thermoregulatory functions, medullary raphé-spinal neurons were studied in urethane-anaesthetized, artificially ventilated, paralysed rats. Extracellular unit recordings were made from a region previously shown to drive the sympathetic supplies to tail vessels and brown adipose tissue. Neurons that were antidromically activated by stimulation across the intermediate region of the upper lumbar cord (the origin of the tail sympathetic outflow) were selected for study.Non-noxious cooling stimuli were delivered to the animal's shaved trunk by circulating cold instead of warm water through a water jacket. Cooling increased the activity of 21 out of 76 raphé-spinal neurons by 1.0 ± 0.2 spikes s−1°C−1 for falls in skin temperature of 3-5 °C below a threshold of 35.0 ± 0.6 °C. Their responses followed skin temperature in a graded manner, and did so whether or not there was any change in core (rectal) temperature.Indirect observations suggested that seven of the neurons that were activated by skin cooling were also activated by falls in core temperature (by 2.1 ± 0.7 spikes s−1°C−1 below a threshold of 36.1 ± 0.7 °C), while the remainder were unaffected by core cooling.An additional 7/76 raphé-spinal neurons showed evidence of inhibition (activity reduced by 2.1 ± 0.5 spikes s−1°C−1) when the trunk skin was cooled.Cold-activated raphé-spinal neurons were found in the nuclei raphé magnus and pallidus, centred at the level of the caudal part of the facial nucleus. Their spinal axons conducted at velocities between 3.4 and 29 m s−1 (median 6.8).Drug-induced rises in arterial pressure partially inhibited the discharge of 6/14 cold-activated raphé-spinal neurons. Weak-to-moderate cardiac modulation (10–70 %) was present in arterial pulse-triggered histograms of the activity of 11/21 cold-activated raphé-spinal neurons, and 6/6 showed evidence of ventilatory modulation (two strongly, four weakly) in pump-triggered histograms.Raphé-spinal neurons responded to cooling in the absence of any change in the electroencephalogram pattern (6/6 neurons).Most cold-activated raphé-spinal neurons responded to noxious tail pinch (13/21 inhibited, 6/21 excited), as did most thermally unresponsive raphé-spinal cells in the same region (19/41 excited, 9/41 inhibited).It is suggested that these cold-activated raphé-spinal neurons may constitute a premotor pathway that drives sympathetically mediated cold defences, such as cutaneous vasoconstriction or thermogenesis. The data are consistent with the hypothesis that a brainstem reflex, with additional descending input signalling body core temperature, may mediate autonomic responses to environmental cooling