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)

Substance P (SP) administered subcutaneously to male and female rats during a neonatal period (days 1-7 after birth), produced long-term effects. Thermal/pain perception and elements of both male and female copulatory behavior were altered. A significant increase in the SP level in the dorsal part of the spinal cord was demonstrated by radioimmunoassay and by micro-fluorescence. The present study indicates that exposure to SP during the neonatal period, when the role of SP in transmission is likely to be established, has biochemical and functional consequences for SP systems in the adult.
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PMID:Neonatal exposure to substance P alters behavioral and substance P levels in the central nervous system of the adult rat. 171 77

Two ganglionic cell groups, located close together and called the internal carotid ganglion, not described before in man, were demonstrated extradurally on the ventrolateral surface of the human internal carotid artery (ICA), where the greater superficial petrosal nerve is joined by the (greater) deep petrosal nerve to form the vidian nerve. The two ganglionic cell groups have fiber connections to the ICA, and consist of 50-70 cells each. By immunohistochemistry the majority of cells in one of the groups were shown to contain vasoactive intestinal polypeptide (VIP) and choline acetyltransferase (ChAT) indicating a parasympathetic function, whereas most cells in the other group contained substance P (SP) and possibly calcitonin gene-related peptide (CGRP), transmitters in pain fibers. Lateral to the intracavernous segment of ICA 10-150 scattered or aggregated VIP- and ChAT-positive cells were found, with fiber connections to the ophthalmic nerve, the ICA, the abducent nerve and the sphenopalatine ganglion. These cells may represent aberrant parasympathetic (sphenopalatine) ganglia, here referred to as cavernous ganglion. By radioimmunoassay substantial amounts of VIP, SP and CGRP were measured in both the extradural and the intracavernous segment of the ICA. Thus, the intracranial segment of the ICA is most likely innervated by parasympathetic and pain fibers from the internal carotid ganglion, sensory fibers from the ophthalmic division of the trigeminal ganglion, and parasympathetic fibers from the sphenopalatine and/or cavernous ganglion. Clinical implications for the activation of these nerves to cause pain, dilatation and edema in this segment of the ICA during attacks of cluster headache and painful ophthalmoplegic syndromes are discussed.
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PMID:Anatomical basis for a parasympathetic and sensory innervation of the intracranial segment of the internal carotid artery in man. Possible implication for vascular headache. 171 60

Skin reactions and itch or burning pain sensations following intradermal injection of the neuropeptide substance P and topical application of the substance P releasing agent mustard oil were studied in 20 atopic dermatitis patients and 20 healthy controls. Changes in skin blood flow were measured with a Laser Doppler flowmeter. Areas of wheal and flare reactions were evaluated planimetrically. Simultaneous with Laser Doppler flowmeter measurements, subjective itch and burning pain ratings were verbally reported on a category partitioning scale at 10-second intervals. Substance P evoked dose-dependent wheal, flare, and itch reactions in both patients and controls. However, substance P doses of 10(-9) -10(-11) mol elicited smaller flares in patients than in the controls whereas the wheal sizes were similar in both groups. Substance P-induced itch ratings were lower in patients at a dose of 10(-10) mol, and the onset of itching was delayed at all substance P levels applied. Mustard oil elicited similar neurogenic inflammatory reactions in both groups, although pain sensations were significantly delayed in atopic dermatitis patients at two mustard oil concentrations, which is further indication of a desensitization of afferent nerve endings contributing to the neurogenic inflammatory reactions in the skin of these patients.
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PMID:Reactions to intradermally injected substance P and topically applied mustard oil in atopic dermatitis patients. 171 19

Substance P (SP) and the excitatory amino acid (EAA) agonists NMDA, kainic acid (KA), or quisqualic acid (Quis) each produce a transient, caudally directed biting and scratching response (CBS) in mice after their intrathecal injection. We have previously shown that repeated injections of SP result in a decrease in the intensity of CBS, or desensitization. The goals of the present study were (1) to determine whether desensitization also develops to the CBS behavior produced by EAAs in the spinal cord, (2) to characterize the role of interneurons in desensitization, and (3) to examine possible interactions between EAAs and SP. While injection of NMDA at 2 min intervals resulted in desensitization to its CBS behavioral effect, behavioral responses to repeated injections of KA or Quis increased in intensity, exhibiting sensitization. The NMDA antagonist DL-2-amino-5-phosphonovaleric acid failed to alter sensitization to either KA or Quis but inhibited behaviors produced by SP and NMDA, suggesting an NMDA-mediated component in SP-induced behavior. Concanavalin A, which is reported to block desensitization to the electrophysiologic effect of Quis, blocked sensitization to the behavioral effects of both Quis and KA. Strychnine, bicuculline, and 5-aminovaleric acid each inhibited desensitization to SP and NMDA, supporting the notion of recruitment of inhibitory transmitters in the attenuation of NMDA and SP activity. Pretreatment with capsaicin selectively inhibited the development of behavioral sensitization to KA, suggesting an involvement of small-diameter C-fibers in the enhancement of responsivity to KA. Consistent with this, pretreatment with SP selectively potentiated the CBS response to KA. The potentiation of KA effects by SP and dependence of KA behavioral sensitization on C-fiber activity suggest a possible mechanism by which EAAs and SP may be involved in the mediation of pain.
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PMID:Behavioral sensitization to kainic acid and quisqualic acid in mice: comparison to NMDA and substance P responses. 171 57

We describe here the pharmacological properties of RP 67580 [(3aR,7aR)-7,7-diphenyl-2-[1-imino-2-(2-methoxyphenyl)ethyl] perhydroisoindol-4-one], a nonpeptide antagonist of substance P (SP). In vitro, the compound was found to inhibit in a competitive manner (Ki = 4.16 +/- 0.59 nM) [3H]SP binding to neurokinin receptors type 1 (NK1 receptors) in rat brain membranes. Contractions induced by SP and septide (a selective NK1 agonist) in guinea pig ileum were competitively inhibited by RP 67580 (pA2 = 7.16 and 7.59, respectively). Moreover, RP 67580 displayed the profile of a specific antagonist of NK1 receptors: it was not active on NK2 and NK3 receptors as seen in binding assays and in isolated preparations of rabbit pulmonary artery and rat portal vein. In the rat, low intravenous doses of RP 67580 totally inhibited the plasma extravasation induced by SP in the urinary bladder (ED50 = 0.04 mg/kg i.v.) and by antidromic electrical stimulation of the saphenous nerve in the hind paw skin (ED50 = 0.15 mg/kg i.v.). This compound was also active in two classical analgesic tests in mice: phenylbenzoquinone-induced writhing (ED50 = 0.07 mg/kg s.c.) and the formalin test (ED50 = 3.7 mg/kg s.c.). Its potency was of the same order as that of morphine. Thus we conclude that RP 67580, a SP antagonist, belongs to a class of drugs that may be useful in the management of various clinical pathologies where pain and neurogenic inflammation are involved.
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PMID:Pharmacological properties of a potent and selective nonpeptide substance P antagonist. 171 49

Cryotherapy has been clinically applied to relieve pain by blocking peripheral nerve function. Clinically, analgesia has been successfully achieved but there is suggestion that permanent pain relief may be accompanied by extended motor and sensory deficits. This study was undertaken to determine the effect of a peripheral cryogenic nerve lesion, i.e., of the sciatic nerve, on behavioral effects and substance P content in the dorsal horn of the spinal cord. In rats, the right sciatic nerve was exposed and cryolesioned using one freeze-thaw-refreeze cycle. In an alternate group, the right sciatic nerve was cut and a 3-mm region was excised. Animals were allowed to recover 7 or 21 days during which their behavior was assessed. Autotomy, an animal's tendency to attack the nerve-injured affected limb, occurred in both the cryolesioned and sectioned groups. They were killed by transcardiac perfusion of fixative and segments L4-S1 were processed for immunocytochemistry. The SP-like immunoreactivity (SPLI) in the right and left dorsal horns was compared and quantitated using a microcomputer imaging device. We utilized a fully automated program to digitize and quantitate the staining of the substantia gelatinosa. There was no significant difference in SPLI in the dorsal horns of the sham-operated controls at either time period. At 7 days the sectioned group demonstrated a 40% decrease in SPLI and 76% decrease at 21 days. In the cryolesioned group, there was a 34% decrease at 7 days and by 21 days there was a 68% decrease in immunoreactivity on the operated side.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autotomy and decreased spinal substance P following peripheral cryogenic nerve lesion. 172 66

A biochemical model of chronic trigeminal facial pain with elevated substance P (SP) and co-dysfunctional dopamine (DA), norepinephrine (NE) and purinergic systems is proposed. The serotonergic system is hypoactive as judged by low 5 hydroxyindoleacetic acid (5HIM). In distinction, intracerebral opioids may not be dysfunctional in facial pain as measured by normal levels of beta endorphin (BE). The neuropeptides somatostatin (SOM), cholecystokinin (CCK), met and leu-enkephalin (MENK, LENK) have very small picogram concentrations in these pain patients, but no definite conclusion can be reached on their role in trigeminal pain, alone or with monoamines, because of the small numbers, both sample size and concentrations. Interpretive obstacles to such human neurochemical studies suggest that future work might move to human clinical trials comodulating SP down, inhibitory peptides (SOM, CCK) up, and enhancing monoamine systems.
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PMID:Trigeminal facial pain: a model of peptides and monoamines in intracerebral cerebrospinal fluid. 172 75

A role for sensitization of nociceptors in the generation of primary hyperalgesia is well documented. More recent work has begun to define a role of an increased excitability of neurons within the spinal cord in the generation of secondary hyperalgesia. The present study demonstrates increased responses of primate spinothalamic neurons following co-administration of N-methyl-D-aspartic acid (NMDA) and substance P (SP) by micro-iontophoresis. Wide dynamic range and high threshold STT neurons in laminae I-VI showed an increased frequency of discharges following application of NMDA which was characterized by a slow onset to peak discharge rate and a slow return to background levels of discharge. Combined application of NMDA with SP resulted in an enhancement of responses to NMDA that often long outlasted the administration of SP. This increase in response of the cells to NMDA was not produced by repeated application of NMDA alone or following combined application of NMDA with an SP analog. NMDA responses were reduced or prevented in all cases by co-application of an NMDA-receptor antagonist. Finally, long-lasting potentiation of NMDA responses by SP was paralleled by enhanced responses to mechanical stimulation of skin. It is proposed that a mechanism involving the combined synaptic release of excitatory amino acids and peptides leads to secondary hyperalgesia.
Pain 1991 Oct
PMID:Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of N-methyl-D-aspartic acid and substance P. 172 95

Neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP) and somatostatin (SS) in dorsal root ganglia (DRG) may play a role in neurogenic inflammation and pain transmission. Adrenal corticosteroids regulate neuropeptide synthesis in some areas of the CNS and may modulate neurogenic inflammation and sensory perception. We have investigated the effects of adrenalectomy and dexamethasone (0.2 mg/kg/day) treatment on neuropeptide content of rat cervical DRG using specific and sensitive radioimmunoassays. In control animals, a differential distribution of neuropeptide was found; SP and CGRP content increased from C4 to C7 in contrast to SS content, which decreased from C4 to C7. Ten days following adrenalectomy, the mean SS content of cervical DRG decreased significantly to 79.6 +/- 4.5% of sham-operated controls. In contrast, SP and CGRP content increased significantly 10 days after adrenalectomy to 134.6 +/- 6.9% and 132.0 +/- 11.6% of sham-operated controls, respectively. The effects of adrenalectomy on CGRP and SS were reversed by administration of dexamethasone. These results suggest that glucocorticoids affect the neuropeptide content of DRG in the adult rat.
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PMID:Effect of adrenalectomy and dexamethasone on neuropeptide content of dorsal root ganglia in the rat. 172 40

Trigeminal nerve fibers in the nasal cavity respond to a variety of volatile chemical stimuli. Some of these trigeminal nerve fibers have been suggested to be capsaicin-sensitive and thus belong to a class of pain receptor rather than constituting a separate class of chemoreceptor. Our current results confirm this suggestion. Trigeminal nerve responses to volatile chemical stimuli were eliminated in rats which were injected with capsaicin on the second day of life. Animals whose nerves were unresponsive to chemical stimuli also exhibited a loss of intraepithelial peptide-immunoreactive fibers in their nasal cavities. The results of this study suggest that trigeminal nerve fibers in the nasal cavity which respond to chemical stimuli may be polymodal nociceptors which contain substance P, calcitonin gene-related peptide, or perhaps other neuropeptides.
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PMID:The effects of neonatal capsaicin administration on trigeminal nerve chemoreceptors in the rat nasal cavity. 172 48


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