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

These studies of cluster headache (CH) focus on two key features of pain transmission: a) sensory nerves when stimulated, as well as the expected afferent transmission, also display an efferent function which affects capillaries, glands, and smooth muscle (of the iris in CH); substance P (SP) and allied transmitters such as Vasoactive Intestinal Peptide (VIP) and Calcitonin Gene-Related Peptide (CGRP) are the main agonists of this dual afferent-efferent function; b) impaired pain transmission (deafferentation-like condition) provokes a rostral spread of neuronal irritability and automatic firing ("quasi epileptic foci") producing a clinical predilection for pain with the generation of "spontaneous" pains along the sensory pathways. The substrates studied in the present experiments are the iris, salivary glands, and nasal mucosa. 1) Iris: the conjunctival instillation of SP induces isocoric miosis both in CH sufferers and in normals, thus excluding gross SP receptoral dysfunction of the iris muscle in CH. Electrical stimulation of extraocular (infratrochlear) endings of the first branch of the trigeminal nerve provokes a miosis, which is significantly less in the symptomatic eye than in the contralateral one. This miosis is ascribed to a retrograde release of SP, induced by electrical stimulation of the trigeminal ophthalmic branch. The relatively poor miosis in the painful eye could correlate with a deficient release of SP from the sensory terminals in the iris. 2) Salivary glands: an increase of substance P-like immunoreactivity is found in the saliva taken from the asymptomatic side, but not from the painful side during a cluster headache attack, thus showing at this level also an asymmetry as previously shown in other head structures. 3) Nasal mucosa: intranasal application of capsaicin, a powerful releaser of SP from sensory terminals, evokes an immediate burning pain in the ipsilateral nasal, ocular, and temporal areas, as well as lacrimation and rhinorrhea. A gradual decrease (tachyphylaxis) of these phenomena is consistently observed after few days of daily nasal administration of capsaicin. When this treatment is applied to CH patients, a rapid decrease in the number and intensity of attacks, and even disappearance of symptoms accompanies the decline of the capsaicin-induced manifestations. Local (nasal) capsaicin, in spite of evoking immediately the same vegetative (rhinorrhea, lacrimation, conjunctival congestion) and in part nociceptive (transient nasal, ocular, temporal burning) phenomena of CH, never has been able to provoke delayed spontaneous-CH like attacks. Such delayed provoked attacks, one of the most pregnant phenomena in CH investigations, are almost constantly evoked by systemic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Substance P theory: a unique focus on the painful and painless phenomena of cluster headache. 168 82

Rats received injections of either capsaicin (50 mg/kg, s.c.) or the capsaicin vehicle at two days of age. When the animals were 90-120 days of age they were implanted with morphine or placebo pellets (s.c.) for 3 (one pellet) or 6 (3 pellets) days. Naloxone (0.4 mg/kg, s.c.) produced no effects in the placebo-pelleted groups but elicited salivation, lacrimation and rhinorrhea in the morphine-treated animals. These abstinence signs were less severe in the morphine-pelleted rats (3- and 6-day groups) that were treated as neonates with capsaicin. However, the neonatal capsaicin treatment increased the number of naloxone-precipitated wet-dog shakes in morphine-dependent rats. The increase was statistically significant in rats treated with morphine for 3 but not 6 days. Since capsaicin induces a long-lasting depletion of substance P and other peptides in peripheral and central neurons, it was concluded that substance P or other related peptides may be involved in the expression of some signs of opioid withdrawal.
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PMID:Neonatal capsaicin modifies morphine withdrawal signs in the rat. 243 61

The involvement of neurokinins, especially substance P, in the opiate withdrawal syndrome was studied by treating rats with drugs that have been reported to increase (captopril) or decrease (capsaicin) tissue levels of substance P. Preliminary experiments with captopril (0.1, 0.3, 1 or 3 mg/kg, SC) showed that the 0.3 mg/kg dose enhanced some of the naloxone-precipitated withdrawal signs. Captopril alone had no effect in the morphine-dependent rat. On experimental days, either saline or captopril (0.3 mg/kg) was injected (SC) immediately before naloxone in morphine-dependent rats that were pretreated (4 to 10 days before the morphine pellet implantation) with either capsaicin (125 mg/kg, SC) or the capsaicin vehicle (N = 8 for each of 4 groups). Capsaicin treatment inhibited the following withdrawal signs: rhinorrhea, lacrimation and salivation. Captopril increased the occurrence of these secretory responses in vehicle-treated but not in capsaicin-treated animals. Other withdrawal signs were not altered by either captopril or capsaicin treatment. The results support the conclusion that substance P and related neurokinins may be involved in the expression of some signs of opioid withdrawal.
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PMID:Captopril and capsaicin modify opioid withdrawal in the morphine-dependent rat. 248 12

1. Topical application of capsaicin to the human nasal mucosa induced a burning sensation and sneezing. A dose-dependent seromucous nasal secretion was also observed. Capsaicin (75 micrograms) was more potent than methacholine (50 mg) in producing nasal secretion, while topical histamine (200 micrograms), substance P (135 micrograms) and calcitonin gene-related peptide (36 micrograms) did not induce rhinorrhea. 2. Pretreatment with either topical ipratropium bromide, systemic dexchlorpheniramine or indomethacin did not influence the effects induced by capsaicin. Topical pretreatment with lidocaine inhibited the painful sensation but failed to block the rhinorrhea. Desensitization to the effects of capsaicin occurred following 4-5 subsequent applications, and full recovery was observed within 30-40 days. 3. It is proposed that the effects of capsaicin in human nasal mucosa are due to excitation of primary afferent neurones that (a) convey burning and painful sensation, (b) evoke a sneezing reflex and (c) induce nasal secretion by releasing transmitter(s) from their peripheral terminals.
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PMID:Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man. 337 Mar 86

The role of neuropeptides in nasal hyperreactivity was examined in guinea pigs by histochemical and pharmacological study. Intranasal application of toluene diisocynate (TDI) induced nasal hyperreactivity symptoms: sneezing and watery rhinorrhea, and decreased histamine content in the nasal mucosa in guinea pigs sensitized with TDI. The immunoreactivity of substance P (SP) and calcitonin gene-related peptide (CGRP) in the nerve terminals in the nasal mucosa was increased after intranasal application of TDI. We also observed a decrease in the immunoreactivity of SP and CGRP, and an increase in their mRNA expression in trigeminal ganglion neurons. These findings indicate that exposure to TDI enhanced the biosynthesis of both SP and CGRP in the trigeminal ganglion neurons and their axonal transportation to the terminals in the nasal mucosa. In animals pretreated with capsaicin before sensitization, TDI did not induce nasal allergy-like behavior and histamine release in the nasal mucosa. Since capsaicin depletes SP and CGRP in the sensory nerves, this finding indicates neuropeptide-mediated histamine release in the nasal mucosa. All these findings suggest that, on exposure to TDI, the antidromic release of SP and CGRP in the nasal mucosa triggers the release of histamine, resulting in the development of symptom of nasal hyperreactivity.
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PMID:[Neurogenic inflammation in nasal hyperreactivity]. 751 48

The functional effects of the intranasal application of exogenous vasoactive intestinal polypeptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) were evaluated in 12 healthy volunteers before and after neutral endopeptidase (NEP) inhibition with phosphoramidon (PA) and angiotensin-converting enzyme (ACE) inhibition with captopril. The three neuropeptides increased nasal airway resistance (NAR) measured by anterior rhinomanometry and superficial capillary blood flow measured by laser Doppler flowmetry (LDF). After pretreatment of the nasal mucosa with PA, the effects of VIP, SP and CGRP on the LDF signal, NAR and mucus production were potentiated, whereas local pretreatment with captopril did not modify these functional effects. These observations suggest that NEP, but not ACE, may participate in the catabolism of neuropeptides when applied directly to the human nasal mucosa. Furthermore, since these neuropeptides induced nasal obstruction, increased blood flow and rhinorrhea, a decreased activity of the enzymes involved in their degradation could be involved in the physiopathology of rhinitis symptoms.
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PMID:Functional effects of phosphoramidon and captopril on exogenous neuropeptides in human nasal mucosa. 754 Dec 10

The article briefly describe the innervation of the human cerebral circulation by nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). The neuropeptides in human cerebral arteries were characterized by radioimmunoassay in combination with HPLC. These neuropeptides mediate contraction (NPY) and dilation (VIP, SP, CGRP). In conjunction with spontaneous attacks of migraine or cluster headache, release of CGRP is seen. With the associated symptoms of nasal congestion and rhinorrhea, VIP is released. Successful treatment may abort the peptide release in parallel with disappearance of headache.
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PMID:Neuropeptides in the cerebral circulation: relevance to headache. 758 22

The role of neuropeptides in nasal allergy was examined in guinea pigs by histochemical and pharmacological study. Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like behaviors: sneezing and watery rhinorrhea, and decreased histamine content in the nasal mucosa in guinea pigs sensitized with TDI. The immunoreactivity of substance P (SP) and calcitonin gene-related peptide (CGRP) in the nerve terminals in the nasal mucosa was increased after intranasal application of TDI. We also observed a decrease in the immunoreactivity of SP and CGRP, and an increase in their mRNA expression in the trigeminal ganglion neurons. These findings indicate that exposure to TDI enhanced the biosynthesis of both SP and CGRP in the trigeminal ganglion neurons and their axonal transportation to the terminals in the nasal mucosa. In animals pretreated with capsaicin before sensitization, TDI did not induce nasal allergy-like behaviors and histamine release in the nasal mucosa. Since capsaicin depletes SP and CGRP in the sensory nerves, this finding indicates neuropeptide-mediated histamine release in the nasal mucosa. All these findings suggest that, on exposure to TDI, the antidromic release of SP and CGRP in the nasal mucosa triggers the release of histamine, resulting in the development of symptoms of nasal allergy.
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PMID:Neurogenic inflammation in nasal allergy: histochemical and pharmacological studies in guinea pigs. A review. 768 May 20

Substance P (SP) is one of several neuropeptides found in nasal mucosa. It exists primarily in sensory afferent neurons, which are best demonstrated by immunohistochemical staining. These substance P-like immunoreactive (SPLI) nerve fibers are unmyelinated C fibers, which connect to the trigeminal ganglion and the spinal trigeminal nucleus. They are found around vessels and seromucinous glands in the submucosa. When the nasal mucosa receives a noxious stimulus, SP is released and acts orthodromically as a comediator of nasal pain, while antidromically it induces vasodilatation, plasma extravasation, mucosal edema, and rhinorrhea. Its antidromic effects have been implicated in vasomotor rhinitis and can be blocked by topical intranasal capsaicin application. Wolf and others have demonstrated in human subjects that vasomotor rhinitis can be blocked up to 1 year by a series of intranasal capsaicin applications. It has not yet been demonstrated that nasal mucous SP levels following noxious nasal stimulus change after intranasal capsaicin pretreatment. Consequently a project was designed to determine whether intranasal capsaicin pretreatment would affect nasal substance P release measured in nasal secretion. Nasal secretion SP levels were measured before and after noxious nasal stimulus in controls and in capsaicin pretreated rats. The difference in measured nasal secretion SP levels were significant (p < 0.05).
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PMID:Capsaicin's effect on rat nasal mucosa substance P release: experimental basis for vasomotor rhinitis treatment. 929 82

Hypertonic saline (HTS) induces bronchoconstriction. Potential mechanisms were evaluated in a human nasal provocation model. Aliquots of normal saline (1 x NS, 100 microliters) and higher concentrations (3 x NS, 6 x NS, 12 x NS, 24 x NS) were sprayed into one nostril at 5-min intervals. Lavage fluids were collected from the ipsilateral and contralateral sides to determine the concentrations of specific mucus constituents. Nasal cavity air-space volume was assessed by acoustic rhinometry (AcRh). The distribution of substance-P-preferring neurokinin-1 (NK-1) receptor mRNA was assessed by in situ reverse transcriptase-polymerase chain reaction. Unilateral HTS induced unilateral dose-dependent increases in sensations of pain, blockage, and rhinorrhea, the weights of recovered lavage fluids, and concentrations of total protein, lactoferrin, mucoglycoprotein markers, and substance P. Contralateral, reflex-mediated effects were minor. There were no changes in IgG or AcRh measurements. NK-1 receptor mRNA was localized to submucosal glands. HTS caused pain with unilateral substance P release. The presumed nociceptive nerve efferent axon response led to glandular exocytosis, presumably through actions on submucosal gland NK-1 receptors. Vascular processes, including plasma exudation, filling of venous sinusoids, and mucosal edema were not induced in these normal subjects.
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PMID:Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans. 1043 Jul 43


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