Local effector functions of capsaicin-sensitive sensory nerve endings : involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides

Capsaicin-sensitive sensory neurons convey to the central nervous system signals (chemical and physical) arising from viscera and the skin which activate a variety of visceromotor and neuroendocrine reflexes integrated at various levels (intramurally in peripheral organs, at level of prevertebral ganglia, spinal and supraspinal level). Much evidence is now available that peripheral terminals of certain sensory neurons, widely distributed in skin and viscera have the ability to release, upon adequate stimulation, their transmitter content. In addition to the well-known "axon reflex" arrangement, the capsaicin-sensitive sensory neurons have the ability to release the stored transmitter also from the same terminal which is excited by the environmental stimulus. The efferent function of these sensory neurons is realized through the direct and indirect (i.e. mediated by activation of other cells) effects of released mediators. The action of released transmitters on postjunctional elements covers a wide range of effects which may have a physiological or pathological relevance. Development of drugs capable of controlling the sensory-efferent functions of the capsaicin-sensitive sensory neurons represent a new and very promising area of research for pharmacological treatment of various human diseases.

The sensory-efferent function of capsaicin-sensitive sensory neurons

Nervous connections between the trigeminal ganglia and cerebral blood vessels have recently been identified in experimental animals and have been termed the trigeminovascular system. Existence of this system in humans is inferential. Trigeminovascular neurons and their peripheral unmyelinated nerve fibers contain the neurotransmitter peptide substance P. Most newly synthesized substance P is transported from ganglion cell bodies to afferent nerve fibers, where depolarization-induced release of neurotransmitter into the wall of the cerebral blood vessel occurs. Substance P dilates pial arteries, increases vascular permeability, and activates cells that participate in the inflammatory response. The relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.

The neurobiology of vascular head pain.

Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers

The tachykinin peptide family

Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs

Depletion by capsaicin of substance P-immunoreactivity and acetylcholinesterase activity from nerve fibres in the guinea-pig heart.

Vasoactive intestinal peptide-like immunoreactivity in nerves associated with the cardiovascular system of guinea-pigs.

Time course of effect of capsaicin on ultrastructure and histochemistry of substance P-immunoreactive nerves associated with the cardiovascular system of the guinea-pig.

The neuropeptides, substance P, vasoactive intestinal peptide (VIP), neuropeptide Y and enkephalin have been found in nerves associated with the heart and blood vessels of a range of mammals, including man. There is also evidence for some cardiovascular nerves with gastrin releasing peptide and neurotensin immunoreactivity. Substance P is in sensory nerves with a widespread distribution to the heart and all vascular beds. In general, large arteries have the densest innervation and the density of nerves decreases as arterial size decreases. In adult guinea-pigs, an adequate treatment with capsaicin causes the degeneration of almost all cardiovascular substance P nerves. Using capsaicin as a tool it has been shown that the substance P containing sensory nerves are not essential for baroreceptor reflexes. VIP nerves also have a widespread distribution, being particularly prominent in the cerebral arteries, uterine arteries and arteries of erectile and secretory tissues. Neuropeptide Y is located in the same cardiovascular nerves as noradrenaline. It is depleted from the nerves by reserpine or 6-hydroxydopamine. Enkephalin nerves have been reported with small arteries in only a few vascular beds.

N.G. Della

Papers

Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs

Depletion by capsaicin of substance P-immunoreactivity and acetylcholinesterase activity from nerve fibres in the guinea-pig heart.

Vasoactive intestinal peptide-like immunoreactivity in nerves associated with the cardiovascular system of guinea-pigs.

Time course of effect of capsaicin on ultrastructure and histochemistry of substance P-immunoreactive nerves associated with the cardiovascular system of the guinea-pig.

Neuropeptides contained in peripheral cardiovascular nerves.