Dynorphin B-Containing Perivascular Axons and Sensory Neurotransmitter Mechanisms in Brain Blood Vessels

Abstract

This is the first report demonstrating the existence of opiate-containing nerve fibers surrounding brain blood vessels. Dynorphin B, a tridecapeptide and potent opiate analgesic, was visualized by immunohistochemistry in guinea pig cerebral arteries comprising the circle of Willis and was measured by radioimmunoassay in canine middle cerebral arteries. This peptide, reportedly present in dorsal root ganglion cells, was observed by others to decrease the depolarization-induced release of substance P from primary sensory axons and, by so doing, to retard the development of neurogenic inflammation in target tissues. Consistent with an indirect action of dynorphin B, this peptide did not relax precontracted canine middle cerebral or basilar artery segments when added in vitro, nor did it modulate receptor-mediated relaxation on the addition of substance P. The presence of opiate-containing axons in or near trigeminovascular nerve fibers suggests novel mechanisms related to the modulation of pain possibly emanating from cerebral vessels.

Cerebrovascular responses to capsaicin in vitro and in situ

“…The trigemino-cerebrovascular system putatively contains substance P, neurokinin A, calcitonin gene-related peptide, gastrin-releasing peptide, dynorphin B and cholecystokinin (Edvinsson et al, 1981;1987a,c;Uddman et al, 1983;1985;Hanko et al, 1985;Liu-Chen et al, 1985;Moskowitz et al, 1986). Substance P, neurokinin A and particularly CGRP are cerebral vasodilators, both in vitro and in situ (Edvinsson et al, 1981;1987a,c;McCulloch et al, 1986), whereas gastrinreleasing peptides, dynorphin B and cholecystokinin have no direct effects on the cerebral vasculature McCulloch & Kelly, 1984;Moskowitz et al, 1986). The cerebrovascular effects of substance P and neurokinin A are markedly attenuated by the substance P analogue, spantide, which does not influence the effects of CGRP (Edvinsson & Jansen, 1987).…”

“…Cerebral blood vessels are innervated by a population of small diameter unmyelinated nerve fibres which originate in the trigeminal ganglion (Mayberg et al, 1984). The trigeminocerebrovascular nerve fibres and perikarya in the trigeminal ganglion contain, often co-localized in the same cellular elements, substance P, calcitonin gene-related peptide (CGRP), cholecystokinin, dynorphin B, neurokinins A and B, as well as putative precursors such as preprotachykinin A (Edvinsson, 1985;Uddman et al, 1985;Hanko et al, 1985;Liu-Chen et al, 1985;Saito & Goto, 1986;Moskowitz et al, 1986;McCulloch et al, 1986;Edvinsson et al, 1987a,b,c). The trigeminocerebrovascular system has long been considered the primary sensory afferent system involved in the transmission to the CNS of nociceptive information of a vascular origin.…”

Epidermoid Tumour of the Posterior Fossa Causing Multiple Facial Pain a Case Report

“…The association between two typical neuralgic pains and a vascular pain led us to discuss the trigeminovascular theory; a connection exists between the trigeminal nuclei and the arteries of the internal and external carotid, and the neuro-transmitter of that system, which is substance P, had algogenic, vasodilating and inflammatory properties. Compression of the fifth and ninth cranial nerves by the tumour could explain the neur-algias; this compression could irritate the fifth cranial nerve and promote the liberation of substance P which could initiate the cluster headache (10)(11)(12)(13).…”

Perivascular Expression and Potent Vasoconstrictor Effect of Dynorphin A in Cerebral Arteries

“…In 1986 Moskowitz and colleagues described the presence of dynorphin B (DYN-B) in guinea-pig cerebral perivascular nerves [15], an observation that has been confirmed subsequently by the same authors in rats [16] and later by others in monkeys [17]. Furthermore, measurable levels of DYN-B were detected in isolated human, canine, bovine and feline cerebral vessels [16].…”