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)

Using in vivo microdialysis in the dorsal spinal cord of the rat, we have previously observed increases in glutamate and aspartate during exposure to a noxious stimulus. The present investigation was designed to determine whether these increases may be mediated by substance P. Infusion of 1 mM of substance P in the dialysis fluid increased the concentrations of glutamate and aspartate, similar to the response seen during noxious stimulation. In addition, substance P also increased the concentrations of the inhibitory amino acids glycine and taurine. Calcitonin gene-related peptide, previously shown to enhance substance P-induced biting and scratching behavior, produced no effect on amino acid release by itself but potentiated the apparent release of taurine by substance P. To assess the importance of substance P-induced amino acid release in sensory processing, we examined the influence of taurine and of excitatory amino acid antagonists on the biting and scratching behavior produced by excitatory amino acids and substance P. Taurine selectively inhibited only substance P-induced biting and scratching while excitatory amino acid antagonists inhibited only excitatory amino acid-induced behavior. To further explore the ability of taurine to inhibit the substance P-induced behavior, 3 tests of nociception were then used. Pretreatment with taurine inhibited the nociceptive-related writhing behavior produced by an intraperitoneal injection of acetic acid in mice but failed to alter the latency of response in the hot plate or tail flick assay.(ABSTRACT TRUNCATED AT 250 WORDS)
Pain 1990 Jul
PMID:Interactions between substance P, calcitonin gene-related peptide, taurine and excitatory amino acids in the spinal cord. 170 Mar 56

The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.
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PMID:Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain. 170 Sep 26

A 31-year-old woman with intractable reflex sympathetic dystrophy experienced nearly complete, though temporary, resolution of pain following 3 weeks of topical capsaicin. We propose that capsaicin may be a useful treatment for reflex sympathetic dystrophy, either by depleting substance P from primary afferent neurons that mediate allodynia, or by modulating sympathetic efferent activity.
Pain 1990 Sep
PMID:Treatment of reflex sympathetic dystrophy with topical capsaicin. Case report. 170 Dec 33

1. To study physiological roles of substance P (SP), gamma-aminobutyric acid (GABA), enkephalins and other endogenous substances, we developed several kinds of isolated spinal cord preparations of newborn rats. 2. In these preparations, various slow responses of spinal neurons evoked by stimulation of primary afferent C fibers were depressed by a tachykinin antagonist, spantide. These results together with many other lines of evidence suggest that SP and neurokinin A serve as pain transmitters in a subpopulation of primary afferent C fibers. 3. Some C-fiber responses in various isolated spinal cord preparations were depressed by GABA, muscimol, and opioid peptides. In contrast, bicuculline (GABA antagonist) and naloxone (opioid antagonist) potentiated the "tail pinch potential," i.e., a nociceptive response of the ventral root evoked by pinch stimulation of the tail in isolated spinal cord-tail preparation of the newborn rat. The latter results support the hypothesis that some primary afferents activate inhibitory spinal interneurons which release GABA and enkephalins as transmitters to modulate pain inputs.
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PMID:Pain and neurotransmitters. 170 58

Peptides have recently been found to function as neuromodulators or neuromediators within nociceptive pathways at central and peripheral sites. More complex and varied in their chemistry compared to "classical" low molecular weight monoamine neurotransmitters, peptides may nonetheless co-exist with these within a single neuron. The biological activity of a peptide results from an "address" segment that permits receptor binding and a "message" segment that initiates reactions within the cell. Opioid peptides (endorphins) are derived from three precursors and act by altering ionic fluxes of potassium or calcium across cell membranes. Nonopioid peptides active in nociception include calcitonin and its gene-related peptide C.G.R.P., bradykinin, substance P, somatostatin, cholecystokinin, and corticotropin-releasing hormone, among others. Ongoing investigations show significant responses of several peptide systems in experimental models relevant to vascular pain. Although the creation of novel peptide analogues has therapeutic promise, their present clinical use must be cautious in light of reports of neurotoxicity after intraspinal application of some of these compounds in animal models.
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PMID:Neuropeptides and pain. 170 17

The possible influence of spinal receptors coupled to Gi/Go regulatory proteins on chronic pain adaptive processes of neural tissues was investigated in normal and arthritic rats. Pain-suffering animals showed an enhanced immunoreactivity to substance P (ir-SP) in the lumbar spinal cord, pons-medulla oblongata region and thalamus. Norepinephrine (NE) levels were increased in the spinal cord, while serotonin (5-HT) was elevated in both spinal cord and midbrain. The intrathecal injection of 1 micrograms pertussis toxin 6 days before sacrifice of rats produced in these arthritic animals a pronounced reduction of ir-SP in the pons-medulla, midbrain and thalamus, but not in the spinal cord. The level of 5-HT was diminished in dorsal spinal cord and midbrain, whereas NE appeared unchanged. In contrast, the toxin only reduced ir-SP of normal rats in the midbrain, without altering the levels of NE or 5-HT, in all the areas analysed. These results suggest the involvement of certain spinal receptors coupled to Gi/Go transducer proteins in processes leading to the elevation of ir-SP and 5-HT in various neural structures of arthritic rats.
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PMID:Effect of intrathecal injection of pertussis toxin on substance P, norepinephrine and serotonin contents in various neural structures of arthritic rats. 170 96

In order to understand the role of substance P (SP) in the brain and the relationship between SP and enkephalins in the electroacupuncture analgesia (EA), we have observed the influence of SP-antagonist, (D-Arg', D-Phe5, D-Trp7.9, Leu11) -SP (DADPDTL) injected intracerebroventricularly (icv) on EA and the change of the level of SP in the brain regions of the rat during EA. We have made a further observations on the influences of the naloxone (NX) on the che change of the content of SP induced by EA and DADPDTL on the increase in Leu-enkephalins (LEK) induced by EA. The Wistar rats were used in the experiment. The latency of the tail flick, immersing the tip of rat tail (4 cm) into hot-water of 50 degrees C, was taken as the pain threshold. The drugs were injected icv via plastic cannulae implanted in the bilateral ventricles. The EA was applied to the point of "Zusanli" (S36). The contents of SP and LEK were determined radioimmunoassay in the hypothalamus, mid-brain, striatum and pons-medulla-oblongata. The pain threshold was increased by 48 +/- 9% (P less than 0.01) after EA. But icv injection of DADPDTL decreased the pain threshold by 14 +/- 7% after EA. The result suggests that DADPDTL can antagonize the effect of EA and that SP in the brain is involved in EA. After EA the contents of SP in the hypothalamus and mid-brain of the rats were decreased by 29% and 28% in comparison with that of the control group respectively (both of them, P less than 0.05), but the contents of SP in the striatum and pons-medulla-oblongata had no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of substance P in electroacupuncture analgesia and its relation to enkephalins in the rat brain]. 170 61

P-Chlorophenylalanine (PCPA) 250 mg/kg IP, was given to a group of rats. 72 hrs later the electro-acupuncture analgesia was tested and substance P (SP) in the brain stem and the lumbar spinal of the rats was determined by RIA. After PCPA injecting the electro-acupuncture no longer caused analgesia but lowered the pain threshold. Meanwhile the level of SP in the brain stem and lumbar spinal did not increased but much lowered than the group of vehicle injection combined with electro-acupuncture. It suggests that by PCPA depleting the 5-HT in CNS and abating the 5-HT-energic descending inhibition the electro-acupuncture no longer causes analgesia but promotes the SP transmitted release. It further suggests that in lower brain stem and spinal transmission of SP was regulated by descending inhibition. Analgesia of electro-acupuncture activates the 5-HT-energic descending inhibition and decreases the nociceptive transmission of SP partly.
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PMID:[The influence of P-chlorophenylalanine on the analgesia of electro-acupuncture and the level of SP in CNS of rats]. 170 62

The present work was carried out to observe the effect of intra-cerebroventricular (icv) injection of monoamine neurotransmitters, enkephalin and morphine on immunoreactive substance P(Ir-SP) contents in hypothalamus, striatum, hippocampus and pain threshold. The results were as follows: (1) After icv or intra-DR (dorsal raphe nucleus) injection of 5-HTP, the content of Ir-SP in hypothalamus significantly decreased and pain threshold markedly increased; After depletion of the 5-HT content in brain by pCPA or destruction of DR, the contents of Ir-SP were remarkably elevated in three brain regions by the former and in hypothalamus, striatum by the later. (2) The Ir-SP levels in the three brain regions and the pain threshold were not affected by the icv injection of NE, however, icv injection of DA caused a increase of Ir-SP concentration in striatum which was reversed by the DA receptor antagonist haloperidol, but without any change of the pain threshold. 7th day after icv injection of 6-OHDA, the content of Ir-SP in striatum significantly reduced. (3) Icv injection of met-enkephalin (MEK) or morphine could increase the Ir-SP levels in hypothalamus, striatum and the pain threshold, and above-mentioned effect of morphine could be prevented by the opioid receptor antagonist naloxone. Icv injection of leu-enkephalin (LEK) had no effects both on Ir-SP contents in three brain regions and the pain threshold.
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PMID:[Effect of monoamine neurotransmitters, enkephalin and morphine on substance P contents of several brain regions and pain threshold in rats]. 170 64

Taxol is a promising new antitumor drug with therapeutic use that is limited by a toxic sensory neuropathy. Taxol is also cytotoxic to dorsal root ganglion neurons in vitro, but this effect is prevented by cotreatment with the trophic protein, nerve growth factor. We sought to develop an animal model and then to determine whether nerve growth factor can prevent taxol neuropathy in vivo. Administration of taxol to mice resulted in a profound sensory neuropathy characterized by decreases in dorsal root ganglion content of the peptide neurotransmitter, substance P, elevated threshold to thermally induced pain, and diminished amplitude of the compound action potential in the caudal nerve. Coadministration of nerve growth factor prevented all of these signs of neurotoxicity. These findings suggest that administration of nerve growth factor may prevent certain toxic sensory neuropathies.
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PMID:Nerve growth factor prevents toxic neuropathy in mice. 170 9


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