Neuropeptides in the sympathetic system: Presence, plasticity, modulation, and implications

Neuropeptides are ubiquitous in the sympathetic system and modulate transmission at the levels of the intermediolateral cell column, sympathetic ganglia, and neuroeffector junctions. Several neuropeptide‐containing pathways from the hypothalamus and medulla modulate excitability of preganglionic neurons. Neuropeptides coexist with norepinephrine or acetylcholine in subpopulations of chemically coded, target‐specific sympathetic ganglion neurons. Neuropeptide Y is colocalized in adrenergic vasconstrictor neurons, whereas vasoactive intestinal polypeptide is colocalized in cholinergic sudomotor neurons. Neuropeptide expression is plastic; during development, neurons that switch from a noradrenergic to a cholinergic phenotype increase expression of vasoactive intestinal polypeptide, somatostatin, and substance P. Preganglionic inputs increase neuropeptide Y and inhibit substance P expression. Sympathetic denervation produces sprouting of sensory fibers containing substance P and calcitonin gene–related peptide in target tissues. Neuropeptides from preganglionic fibers (e.g., enkephalin) and primary afferents (e.g., substance P, vasoactive intestinal polypeptide) modulate transmission in sympathetic ganglia. Neuropeptide Y produces vasoconstrction, prejunctional inhibition of norepinephrine release, and postjunctional potentiation of norepinephrine effects. Plasma neuropeptide Y increase during intense sympathoexcitation, hypertension, and pheochromocytoma. Dystrophic neurites containing neuropeptide Y occur in human sympathetic ganglia during aging, diabetes, and dysautonomia. Sympathetic neuropeptides may thus have important clinical implications.