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)

The effects of an N-terminal fragment of substance P, substance P-(1-7) [SP-(1-7)], on the responses of dorsal horn nociceptive neurons to N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) were tested by combined single-unit extracellular recordings/microiontophoresis. While SP-(1-7) had no effects when applied by itself, it was a potent and long-lasting modulator of both NMDA- and AMPA-mediated excitation of spinal dorsal horn nociceptive neurons. NMDA responses were transiently decreased (by an average of 36% of control at minimum) by SP-(1-7) followed by a more sustained increase (by 76% at maximum). In contrast, AMP responses were only increased by SP-(1-7) (by 81% at maximum). It is hypothesized that the actions of SP-(1-7) on excitatory amino acid (EAA) responses of dorsal horn nociceptive neurons reflect a novel mechanism by which SP and EAAs interact to modulate pain transmission.
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PMID:Modulation of N-methyl-D-aspartate and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) responses of spinal nociceptive neurons by a N-terminal fragment of substance P. 138 65

Although it is known that pain in the forehead may be induced by neck abnormalities, the actual neck-head connections responsible for development of pain in trigeminal areas are poorly understood. Vasoactive neuropeptides released from sensory fibres, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been considered as important elements in headache pathophysiology. The levels of CGRP-like immunoreactivity (LI) were measured bilaterally in the jugular blood (52 rats) and intraocular aspirates (66 rats) following electrical stimulation of the left greater occipital nerve, and in the jugular blood of 13 control animals. One-third of the stimulated rats had varying combinations of conjunctival injection, tearing, diminished eye aperture and miosis or mydriasis on the stimulated side. The other two-thirds exhibited no ocular signs. Significantly lower levels of CGRP-LI were present in the jugular blood on the stimulated side in comparison with control rats. There was comparatively lower CGRP-LI on the non-stimulated side as well, but to a lesser extent. Significant differences between the stimulated and the non-stimulated side were present, particularly in the tearing/diminished eye cleft group. It is proposed that stimulation of the rat GON inhibits the trigeminal system (reduction of CGRP-LI) and possibly activates parasympathetic fibres (ocular changes).
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PMID:Reduction of calcitonin gene-related peptide in jugular blood following electrical stimulation of rat greater occipital nerve. 142 57

Synovial tissue was obtained from 18 knees with medial compartmental osteoarthritis (OA) and from 20 knees on which a high tibial osteotomy had been performed. Neuropeptides were stained with a specific avidin-biotin-peroxidase method. Comparisons were made of the incidence of staining as well as the location of staining within the synovia (medial, lateral, and suprapatellar regions). The results showed that the synovium had an extensive neural network of both the somatic and autonomic nervous systems. In the medial synovium of the preoperative knees, the neuropeptides were found in abundance. An especially strong response for substance P (SP) and calcitonin gene-related peptide (CGRP) was observed at the free nerve endings. However, the postoperative incidence of SP-positive free nerve endings was reduced to 54% of the preoperative amount and the inflammation subsided in the medial region. These findings suggested that free nerve endings containing SP might be mainly involved in the inflammation and pain of OA.
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PMID:[Immunohistochemical study on the effect of high tibial osteotomy on the distribution pattern of neuropeptides in the synovium of the osteoarthritic knee]. 144 24

Coracoacromial ligament and periligamentous fatty and loose connective tissue obtained during Neer's acromioplasty in patients with chronic painful rotator cuff tendinitis/impingement syndrome was studied for possible signs of inflammatory involvement and for the presence of neuropeptide-containing nerves, using routine histology and immunoperoxidase staining. No accumulations of inflammatory cells were found in the tissues studied. The dense ligamentous tissue proper was practically aneural, as was seen in staining for the generalized neuronal markers protein gene product 9.5 and synaptophysin. In contrast, the periligamentous fatty and loose connective tissue was innervated. Almost all nerves in such tissue contained C-flanking peptide of neuropeptide Y, whereas substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide-containing nerves were not found at all or were extremely rare. This suggests that the coracoacromial ligament is not a target of irritative inflammation. In the periligamentary sheath, nerves containing markers for the C-type nociceptive pain fibers were practically absent and all local nerves were postganglionic sympathetic vaso-regulatory nerves.
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PMID:Immunoreactive neuropeptide nerves in ligamentous tissue in chronic shoulder pain. 144 43

The innervation of lumbar facet capsule and ligamentum flavum was investigated using antisera to a general neuronal marker protein gene product (PGP) 9.5 and to peptide markers of sensory nerves (calcitonin gene-related peptide [CGRP] and substance P) and autonomic nerves (vasoactive intestinal polypeptide [VIP] and C-flanking peptide of neuropeptide Y [CPON]). In the facet capsule (n = 14), PGP 9.5 and CGRP-immunoreactive nerves occurred in 12 and five specimens, respectively, both around blood vessels and as free fibers in the stroma. Free fibers immunoreactive for substance P or VIP were noted in three and five specimens, whereas in nine specimens there were CPON-immunoreactive nerves located perivascularly. There was no immunoreactivity in the ligamentum flavum. This study provides further evidence that the facet capsule but not the ligamentum flavum has substantial innervation by sensory and autonomic nerve fibers and has a structural basis for pain perception.
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PMID:Morphological basis for back pain: the demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum. 153 Jul 99

A patient is described with a 17-year history of intractable left-sided facial pain. The pain occurred daily in 5 sec spasms to a maximum of one every 2-3 min and was restricted to the left upper face. It was associated with rhinorrhoea on the left and often with ipsilateral facial flushing. Conventional therapy, including carbamazepine, baclofen and three posterior fossa explorations, had not provided lasting relief. Local facial stimulation by tapping a painful trigger point led to both pain and flushing of the face ipsilaterally. During this flushing, blood was collected and assayed using sensitive radioimmunoassays for several neuropeptides (neuropeptide Y, substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide). A marked (119%) increase in calcitonin gene-related peptide was noted in the external jugular vein blood ipsilaterally during the flushing with no change in the other peptides measured. To quantitate the effect of calcitonin gene-related peptide on human extracranial vessels, standard pharmacological procedures were used to examine the potency of the peptide as a vasodilator of human facial artery. The IC50 of calcitonin gene-related peptide for the prostaglandin F2 alpha-precontracted human facial artery was 10(-9) mol/l. The relevance of these observations to the clinical problem of migraine is considered.
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PMID:Cutaneous sensory stimulation leading to facial flushing and release of calcitonin gene-related peptide. 155 59

Esophageal pain is transmitted via the sympathetic nervous system to the spinal cord, in which pain from visceral and somatic sources ascends to higher centers in the brain. Primary afferent neurons are bipolar, with the peripheral end specialized to be a sensory receptor. Nociceptors of somatosensory afferents are free nerve endings that can be activated by mechanical, thermal, or chemical stimuli. Esophageal nociceptive neurons have not been specifically identified but probably are also free nerve endings. Most esophageal spinal mechanoreceptors have been shown to be nociceptive. Some esophageal mechanonociceptors have a wide dynamic range and respond to physiologic and painful stimuli, while others have a high threshold of stimulation and are solely nociceptive. Esophageal spinal afferents have their cell bodies in the dorsal root ganglia and contain substance P and calcitonin gene-related peptide. These putative neurotransmitters are transported in both the peripheral and central directions of bipolar afferent neurons. Primary afferent neurons are likely to also contain an excitatory amino acid neurotransmitter such as glutamate. Centrally, nociceptive primary afferents terminate on neurons in specific layers of the dorsal horn of the spinal cord. Convergence of multiple visceral afferents with somatic afferents onto the same dorsal horn neurons may explain referred pain. A patient's inability to distinguish esophageal from cardiac pain may be due to convergence of pain pathways. Second-order neurons in the dorsal horn project in the anterolateral system to the brain. Within the anterolateral system, nociception ascends in the spinothalamic, spinoreticular, and spinomesencephalic tracts. The thalamus relays fast pain to the postcentral areas of the parietal lobe of the cortex. Pathways to the reticular formation are slow and may mediate the increased arousal that occurs in response to pain. The spinomesencephalic tract projects to midbrain sites including the periaqueductal gray. Organ-specific pathways in the brain have yet to be defined, but neuroanatomic tracing techniques employing neurotropic viruses are being developed. The perception of pain can be influenced at multiple levels, such as the receptor in the esophagus, the synapses in the dorsal horn of the spinal cord or thalamus, or the cortex. A fundamental mechanism of modulating nociception is descending inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of esophageal pain. 159 55

Small vasoactive neurotransmitter molecules with a long evolutionary history of involvement in biological defense and inflammation play important roles in the up-regulation and down-regulation of the immune response and with similar effects on neuronal and lymphocyte transmembrane signaling molecules and mechanisms. The longest acting of these stimulatory molecules on lymphocyte traffic, substance P and bradykinin, also are transmitters of impulses relating to heat and pain. Heat and pain have been primordial stimuli to learning and memory--immunological as well as CNS.
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PMID:Neurovascular immunology: a 25-year odyssey. 160 88

Normal nociceptors are sensitized by hyperalgesic mediators such as eicosanoids and tachykinins. The possibility that these mediators contribute to hyperalgesic pain associated with neural injury was investigated by examining their effects on the excitability of injured afferent nerve endings. In amounts that sensitize normal nociceptors and are hyperalgesic in normal skin, the eicosanoids prostaglandin I2 (PGI2), and 8(R),15(S)-dihydroxyicosatetraenoic acid (8(R),15(S)-diHETE) both excited some C-fibers in chronic neuromas of rat sciatic nerve. In contrast, the selective tachykinin-receptor agonists septide and senktide did not excite C-fibers. None of the mediators affected A-fibers. We conclude that PGI2 and 8(R),15(S)-diHETE may contribute to post-injury pain and hyperalgesia by an action on injured afferent endings.
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PMID:Eicosanoids, but not tachykinins, excite C-fiber endings in rat sciatic nerve-end neuromas. 161 Oct 31

A comprehensive high-performance liquid chromatographic, radioimmunoassay, and enzymatic degradation scheme has been developed to analyze several intact neuropeptides and the corresponding peptides created by in vivo enzymolysis of precursors to study neuropeptides in human lumbar cerebrospinal fluid (CSF) and to test the hypothesis that defects in the metabolism (synthesis, degradation) of neuropeptide precursors, neuropeptides, and metabolites play a role in low back pain. CSF samples were obtained from three different patient groups: controls (C), whose low back pain was relieved without lidocaine; pharmacological responders (PR), whose pain was relieved by lidocaine and who were candidates for surgery; and pharmacological non-responders (PNR), whose pain was not relieved by lidocaine and a mid-thoracic anesthetic, and who were not candidates for surgery. The metabolic activity involved during synthesis and degradation of the peptides was assessed by measuring intact, native neuropeptide immunoreactivity in pre-incubated and post-incubated CSF samples, where samples were incubated at 37 degrees C for 1 h. Pre-incubation radioimmunoassay measurements reflected the content of intact peptides present in lumbar CSF at the time of sampling, and post-incubation measurements assayed the amount of peptide that had remained embedded within its precursors [cryptic methionine enkephalin (ME)] and that had been released by the action of CSF peptidases. Significant differences were found in post-incubation samples for the amount of proenkephalin A [ME, leucine enkephalin (LE)] and tachykinin [substance P (SP)] peptides. For example, significant differences were observed for ME-like immunoreactivity (C versus cryptic), SP-like immunoreactivity (PNR versus PR), and LE-like immunoreactivity (PR versus C). No significant differences were observed among the peptides within the pre-incubation samples.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of proenkephalin A, proopiomelanocortin and protachykinin neuropeptides in human lumbar cerebrospinal fluid by reversed-phase high-performance liquid chromatography, radioimmunoassay and enzymolysis. 162 97


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