Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Cephalalgia 1986 Jun
PMID:Dynorphin B-containing perivascular axons and sensory neurotransmitter mechanisms in brain blood vessels. 242 98

It has been suggested that a number of peptides may be involved in the transmission of pain. In order to evaluate the possible role of peptides in the development of headache, we have, in the present study, examined the presence of nerve fibres containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in human temporal and occipital tissues. In the skin, delicate VIP, SP and CGRP fibres occur beneath the epidermis, sometimes running into the folds of the dermal ridges. In deeper layers of the dermis, small blood vessels are occasionally surrounded by single nerve fibres containing NPY, VIP, SP and CGRP. Large temporal and occipital arteries are surrounded by a meshwork of such fibres. In addition, NPY and VIP fibres are seen around sweat glands and hair follicles. Smooth muscle bundles in the dermis are surrounded by VIP fibres, whereas the temporal muscle per se is devoid of such fibres.
 ...
PMID:Peptide-containing nerve fibres in human extracranial tissue: a morphological basis for neuropeptide involvement in extracranial pain? 243 70

Substance P, present in primary sensory neurones, seems to take part in nociceptive transmission within the trigeminal system. Substance P, released by peripheral axons of these neurones, induces vasodilatation, plasma extravasation, miosis, conjunctival and nasal congestion. All these effects bear some similarity to symptoms of cluster headache and migraine attack. Opiates and somatostatin inhibit the release of substance P from primary sensory neurones and relieve both pain and autonomic symptoms of cluster headache attack. Plasma substance P-like immunoreactivity was decreased during spontaneous attack of cluster headache and migraine and during histamine precipitated attack of cluster headache. Taken together these data suggest that substance P and endogenous opioids could be implicated in the pathophysiology of cluster headache and migraine.
 ...
PMID:Substance P and enkephalins: a creditable tandem in the pathophysiology of cluster headache and migraine. 243 12

Substance P-like immunoreactivity (SP-LI) was measured by radioimmunoassay in iris, choroid, and retina obtained from men after death. Although present in different amounts, SP-LI, eluting as authentic SP or SP sulfoxide in the high-performance liquid chromatography system, was found in the three ocular structures. The retina contained higher concentrations of SP-LI than the iris and choroid. The possible functional involvement of iris SP was studied in 22 episodic cluster headache (CH) patients by using the anticholinesterase agent echothiophate iodide (EI), which also induces an atropine-resistant miosis, putatively due to release of SP from trigeminal sensory neurons. In CH patients EI eye drops instilled into both eyes provoked a prolonged miosis with a more marked response in the pupil of the symptomatic eye. It is proposed that the hyperfunction of SP-containing neurons may coexist with the previously documented sympathetic hypofunction in the innervation of the symptomatic pupil of CH.
Cephalalgia 1988 Mar
PMID:Substance P in the human iris: possible involvement in echothiophate-induced miosis in cluster headache. 245 18

The trigeminal ganglion was activated, in humans by thermocoagulation as part of the treatment of trigeminal neuralgia and in cats by electrical stimulation, and blood samples were taken from the external jugular vein for estimates of plasma levels of substance P and calcitonin gene-related peptide (CGRP). In those patients who were noted at the time of coagulation to have flushed there were marked elevations of the local (cranial) levels of both peptides. However, in the nonflushing patients no changes in the peptide levels were observed. Parallel experiments in the cat revealed that the levels of substance P-like and CGRP-like immunoreactivity were increased during electrical stimulation of the trigeminal ganglion. The observation of elevation of substance P-like and CGRP-like immunoreactivity after activation of the nociceptive afferent system of the head provides new insights into a putative role of peptides in the pathophysiology of migraine and cluster headache, and suggests new areas of possible therapeutic intervention.
 ...
PMID:Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. 245 66

Sensory axons from the trigeminal ganglion (V) innervate cephalic blood vessels and use the preprotachykinin gene products, substance P (SP) and neurokinin A (NKA), as putative neurotransmitters conveying nociceptive information. Blood in the subarachnoid space is accompanied by severe headache. We now report that this painful stimulus, which should enhance activity in V, specifically alters tachykinin peptide and mRNA levels in V and perivascular axons. Marked reductions in SP levels were observed in basilar artery segments within 4 hours after intracisternal blood injection which persisted for 48 hours and recovered by 7 days. SP peptide levels in V were elevated by 49% two days after blood injection. The changes in SP peptide levels were accompanied by increases in ganglionic content of the preprotachykinin mRNA that codes for the peptide. Blood-induced peptide depletion in arteries and subsequent increases in peptide and mRNA in V are consistent with increased neuronal activity and enhanced neuropeptide release. These results implicate the tachykinin-utilizing trigeminovascular neurons in the sequelae of subarachnoid hemorrhage.
 ...
PMID:Subarachnoid blood and headache: altered trigeminal tachykinin gene expression. 246 32

To further define the sensory projections to the circle of Willis, we measured concentrations of immunoreactive substance P in pial arteries of cats following either bilateral removal of the C1-3 dorsal root ganglia (six cats) or bilateral removal of the trigeminal ganglia (three cats). Removal of the dorsal root ganglia decreased concentrations of the tachykinin substance P in the vertebral artery and the basilar artery and its branches by 72% and 50-66%, respectively. Bilateral removal of the trigeminal ganglia decreased substance P concentrations in all forebrain vessels including the rostral basilar artery, although only concentrations in the anterior cerebral artery were significantly lower than those in unilaterally lesioned cats (p less than 0.01). Hence, the vertebrobasilar artery and its tributaries are invested by substance P-containing fibers originating from the upper cervical dorsal root ganglia, and the anterior cerebral artery is innervated by both trigeminal ganglia. If a similar anatomy exists in humans, our data provide an explanation for the occipital localization of headaches arising from the vertebrobasilar arteries and for bilateral headaches following stimulation of the anterior cerebral artery.
 ...
PMID:Contributions from the upper cervical dorsal roots and trigeminal ganglia to the feline circle of Willis. 246 9

Trigeminal sensory innervation of cerebral vessels and the surrounding dura is responsible for most intracranial head pain. Small-diameter fibers containing substance P (Sub P) have been observed in the periadventitia around feline cerebral blood vessels, and it has been suggested that these fibers are the trigeminal substrate for vascular pain associated with cluster and migraine headaches. Calcitonin gene related peptide (CGRP) coexists with Sub P in some of these fibers and with some Sub P containing neurons in the trigeminal ganglion. In addition, a population of trigeminal neurons containing CGRP but not Sub P has been observed. We now report that the population of trigeminal ganglion cells projecting to the cerebral vasculature is enriched in CGRP-containing neurons, and especially in the population of neurons containing CGRP and not Sub P. Using retrograde tracing of fluorescent tracers combined with immunocytochemistry after explant culture, we found approximately 32% of trigeminal ganglion cells projecting to the cerebral vasculature contained CGRP. Approximately 18 and 17% of these cells contained Sub P and cholecystokinin (CCK), respectively. The 32% of ganglion cells projecting to the cerebral vasculature that contain CGRP stands in contrast to the 12% CGRP positive seen in the population of ganglion cells projecting out to another target (the forehead), and the 21 and 23% CGRP positive observed in the mandibular branch and entire ganglion, respectively. Sub P and CCK are not enriched in the trigeminal innervation of the vasculature compared with their presence in cells throughout the ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries. 247 Aug 72

According to new findings, Sluder's neuralgia, cluster headache and sympathetic neuralgia in the face are likely to be of vascular origin from the branches of the external carotid artery. These vessels receive multiple innervation: sympathetic (constricting), parasympathetic (vasodilator) and through C-fibre liberating substance P. In addition enkephalins, known to act as antagonists to substance P, have been found in the vessels of the external and the internal carotid artery. The equilibrium between sympathetic and parasympathetic fibres, between C-fibres and local enkephalins may be disturbed by various mechanisms. An excess of the sympathetic or parasympathetic activity may not only cause changes of vascular tone but also induce the liberation of substance P. In general, the atypical facial neuralgias are self-limiting or may present with an intermittent course. In chronic and drug-resistant cases surgical interventions can be helpful. The trigeminal nerve is the first target, as all C-fibres from the head, including the vessels, reach the trigeminal nerve. Of less importance for surgical intervention is the pterygopalatine ganglion, which is not only parasympathetic, but contains also sympathetic and C-fibres from the mucosa of nose and orbit.
 ...
PMID:[So-called atypical facial neuralgias]. 247 89

Leakage of 125I-bovine serum albumin was measured in rat dura mater, conjunctiva, eyelid and lip, after unilateral electrical stimulation of the trigeminal ganglion. In one animal, 99Tc-human serum albumin leakage was imaged in ipsilateral facial tissues. Pretreatment with indomethacin 1 mg/kg i.p. decreased leakage in dura mater but not in extracranial tissues. When extravasation was expressed as a ratio of stimulated to unstimulated sides, indomethacin 1 mg/kg, or acetylsalicylic acid 50 mg/kg decreased this ratio from 1.80 to 1.27 (P less than 0.01) or from 1.84 to 1.21 (P less than 0.01), respectively. Dexamethasone (1 mg/kg i.p. tid X 1 day) caused only a very small decrease. Only large doses of indomethacin (10 mg/kg) or acetylsalicylic acid (50 mg/kg) reduced substance P (SP)-induced leakage in the dura. The latter results suggest that both drugs block plasma extravasation by acting on neuropeptides-induced changes in vascular permeability and/or smooth muscle contractility. However, inhibition of SP release from sensory axons cannot be excluded at concentrations which block neurogenic plasma extravasation but not SP-induced plasma leakage. Together, these results provide a possible mechanism for the therapeutic effects of indomethacin and acetylsalicylic acid in headache.
 ...
PMID:Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater. 277 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>