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

Specialized functional pathways are the building blocks of the autonomic nervous system

The autonomic nervous system supplies each type of target organ via separate pathways which consist of sets of pre- and postganglionic neurones with distinct patterns of reflex activity. This has been firmly established for the lumbar sympathetic nervous system to skin, skeletal muscle and viscera, for the thoracic sympathetic outflow to the head and for several parasympathetic systems. In principle, that was already known by Langley. The specificity of the messages that these pathways transmit from the central nervous system arises from integration within precisely organized pathways in the neuraxis. The messages travel along discrete functional pathways and are transmitted to the target tissues via close neuroeffector junctions. Integration in the periphery occurs within each pathway, both in ganglia and at the level of the effector organs. We still need to understand how the central messages get through without distortion and how they control the diverse functions of the vasculature and viscera

The time course of the development of the sympathetic innervation of the vasculature of the rat tail

The development of the sympathetic innervation of the tail vasculature in the rat has been examined using catecholamine fluorescence and immunohistochemical techniques to demonstrate tyrosine hydroxylase (TH) and neuropeptide Y (NPY). The tail was found to be largely devoid of noradrenergic terminals at birth. At the earliest ages, axons within nerve trunks amd paravascular axon bundles showed high levels of catecholamine fluorescence, but this virtually disappeared as the innervation of the effectors was achieved. The perivascular plexus on the caudal artery was established over the first six postnatal weeks along a rostrocaudal gradient which was retained in the adult, i.e. proximal regions were more densely innervated than distal ones. The innervation of the rest of the vasculature developed relatively late during this period, with the exception of the arteriovenous anastomoses present in the distal half of the tail. These became innervated about 10 days earlier than the adjacent caudal artery at the same levels, and received a much denser innervation in the adult. At all developmental stages, distributions of TH- and NPY-immunoreactive nerve fibres were identical to those seen with catecholamine fluorescence. The sequence of development suggests that the different vascular targets are innervated by subsets of sympathetic neurones having the same neurochemistry but developing independently

The effects of catechol on various membrane conductances in lumbar sympathetic postganglionic neurones of the guinea-pig

The effects of catechol on membrane properties in lumbar sympathetic postganglionic neurones isolated from guinea-pigs were studied in vitro in current and voltage clamp using single intracellular microelectrodes. Neurones with properties characteristic of two previously described classes of neurone (phasic and tonic) were studied. Catechol (3-12 mM) produced a few mV depolarization and a dose-dependent increase in membrane resistance which were both larger in tonic than in phasic neurones. In the presence of catechol, both phasic and tonic neurones fired only a single action potential at the beginning of a maintained depolarizing current step. In both neurone types, catechol reduced action potential amplitude and slowed its time course. The peak of the after-hyperpolarization became delayed and reduced in amplitude, particularly in tonic neurones. The time constant of inactivation of I(A) was reduced by catechol without change in the voltage sensitivity of activation or inactivation; IC was 3 mM in phasic and 4 mM in tonic neurones. Catechol also blocked a slow voltage-activated K current (resembling I(D)) that was present in many tonic neurones. Catechol did not modify the slow calcium-activated potassium current (gKCa1) or the anomalous rectifier; neither did it appear to affect the fast calcium-activated potassium current (I(C)) or the delayed rectifier. Catechol did not change the overall rate of spontaneous synaptic activity nor enhance the release of quanta of ACh from preganglionic terminals evoked by nerve stimulation. We conclude that, in addition to blocking I(A), catechol blocks the slow I(D)-like current in sympathetic neurones. It also has a profound effect on the action potential probably by increasing inactivation of voltage-dependent Na channels. The change from tonic to phasic discharge in tonic neurones cannot be attributed solely to its effects on I(A)

Tetrodotoxin-resistant impulses in single nociceptor nerve terminals in guinea-pig cornea

Extracellular recording techniques have been used to study nerve impulses in single sensory nerve terminals in guinea-pig cornea isolated in vitro.Nerve impulses occurred spontaneously and were evoked by electrical stimulation of the ciliary nerves.The nerve impulses were identified as originating in polymodal receptors, mechano-receptors or ‘cold’ receptors. All three types are believed to be nociceptors.Tetrodotoxin (TTX, 1 μm) blocked nerve impulses evoked by electrical stimulation of the ciliary nerves. However, ongoing and/or naturally evoked nerve impulses persisted in the presence of TTX in all three types of receptors. Lignocaine (lidocaine; 1 mm) blocked all electrical activity.TTX-resistant sodium channels therefore play a major role in generating the action potentials that signal pain to the brain