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)

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

Substance P, a neuropeptide associated with pain perception, is widely distributed in the central nervous system and is decreased in the cerebrospinal fluid of chronic pain patients as compared with that of healthy human volunteers. In this study, we have demonstrated the presence of immunoreactive substance P in saliva and further, that both saliva and plasma levels of immunoreactive substance P are lower in patients with chronic low back pain than in healthy human volunteers. To our knowledge, this is the first time that substance P has been identified in human saliva. These findings, together with the noninvasive nature of saliva collection, suggest that substance P in saliva may be useful as an alternative neurochemical correlate of chronic low back pain when collection of cerebrospinal fluid and plasma samples for substance P analysis is unacceptable or inappropriate.
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PMID:Immunoreactive substance P is decreased in saliva of patients with chronic back pain syndromes. 168 90

Cells of the immune system synthesize prolactin and express mRNA and receptors for that hormone. Interleukin 1, interleukin 6, gamma interferon, tumor necrosis factor, platelet activator factor, and substance P participate in the release of prolactin. This hormone is involved in the pathogenesis of adjuvant arthritis and restores immunocompetence in experimental models. In vitro studies suggest that lymphocytes are an important target tissue for circulating prolactin. Prolactin antibodies inhibit lymphocyte proliferation. Prolactin is comitogenic with concanavalin A and induces interleukin 2 receptors on the surface of lymphocytes. Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes. Cyclosporine A interferes with prolactin binding to its receptors on lymphocytes. Hyperprolactinemia has been found in patients with systemic lupus erythematosus. Fibromyalgia, rheumatoid arthritis, and low back pain patients present a hyperprolactinemic response to thyrotropin-releasing hormone. Experimental autoimmune uveitis, as well as patients with uveitis whether or not associated with spondyloarthropathies, and patients with psoriatic arthritis may respond to bromocriptine treatment. Suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine A with significantly less toxicity. Prolactin may also be a new marker of rejection in heart-transplant patients. This body of evidence may have an impact in the study of rheumatic disorders, especially connective tissue diseases. A role for prolactin in autoimmune diseases remains to be demonstrated.
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PMID:Prolactin, immunoregulation, and autoimmune diseases. 206 74

The activity levels of a dynorphin converting enzyme (DCE), a substance P endopeptidase (SPE) and a substance P alpha-amidating enzyme (SP-GLYE) were measured in the cerebrospinal fluid (CSF) of 90 patients with chronic low back pain, sciatica and neurological signs of rhizopathy. The DCE activity was significantly higher in men than in women. Age was related to the DCE activity independent of sex, i.e., older patients had higher enzyme activity. The activities of two substance P converting enzymes were not related to sex or age. Self-reported pain experience and affective covariates (anxiety, depression, hostility, somatization) of pain, and myelography data were not found to be related to the enzyme activity levels once adjustment had been made for sex and age. The activity levels of the enzymes measured here had no predictive value for the long-term outcome of rehabilitation and therapy at the 5-year follow-up of the patients. The sex difference in DCE activity provides further evidence in favor of the role of gender in the psychoendocrine coping with pain distress.
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PMID:Neuropeptide converting enzyme activities in CSF of low back pain patients. 215 Aug 78

An indirect immunofluorescence method was utilized to identify substance P-like immunoreactive (SPLI) and neurofilament protein immunoreactive (NFIR) fibers in the lumbar facet joint capsule and supraspinous ligament of the rabbit. The results demonstrated a large population of NFIR fibers, indicating that these tissues are richly innervated, and a smaller population of SPLI fibers. In some fibers, neurofilament protein and substance P were colocalized. The data suggest that the facet joint capsule and the supraspinous ligament contain SPLI nociceptive fibers that could be a source of low back pain.
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PMID:Localization of substance P and neurofilament immunoreactive fibers in the lumbar facet joint capsule and supraspinous ligament of the rabbit. 246 64

Substance P-like immunoreactivity (SP-LI) of the cerebrospinal fluid was measured by radioimmunoassay in 40 patients with lumbar disc herniation (hernia group), and in 10 patients with no low back pain and no leg symptoms (control group). The SP-LI was significantly higher in the hernia group (5.49 +/- 3.01 pg/ml) than in the control group (2.05 +/- 0.52 pg/ml) (p < 0.01). In the hernia group, the SP-LI was significantly higher in patients with severe pain in the lower extremities than in those with only mild pain. As the SP-LI was found to be correlated with the severity of pain, it was considered to be a useful index of pain. As for the correlation of SP-LI with the hernia type, the SP-LI was significantly higher in patients with transligamentous extrusion type hernia than in those with protrusion type hernia. This result suggested that the release of substance P was increased with marked compression on the dorsal root.
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PMID:[Substance P-like immunoreactivity in cerebrospinal fluid in lumbar disc herniation]. 754 Jan 93

Sixteen adult human lumbar spine facet joints were harvested from patients undergoing various lumbar spine procedures. Diagnoses included degenerative disc disease, adult spinal deformity, facet joint degenerative arthritis, and degenerative spondylolisthesis. Facet joints were processed for routine hematoxylin and eosin staining. Immunohistochemical analysis was performed using a monoclonal antibody to substance P. All facets grossly exhibited evidence of degenerative disease, including cartilage surface irregularity and fibrillation. Histological examination of facets obtained from patients with degenerative spinal conditions demonstrated erosion channels extending through the subchondral bone and calcified cartilage into the articular cartilage. Immunostaining showed the presence of substance P-positive nerve fibers within these erosion channels, and also within marrow spaces. The presence of substance P nerve fibers within subchondral bone of degenerative lumbar facet joints implicates this type of joint in the etiology of low back pain.
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PMID:Substance P innervation of lumbar spine facet joints. 769 Jan 59

Idiopathic low back pain has confounded health care practitioners for decades. Although there has been much advance in the understanding of the biomechanics of the lumbar spine over the past 25 years, the cellular and neural mechanisms that lead to facet pain are not well understood. An extensive series of experiments was undertaken to help elucidate these mechanisms and gain a better understanding of lumbar facet pain. Biomechanic and neuroanatomic studies were performed in human cadaveric facet joints and neurophysiologic studies were performed in New Zealand White rabbits. These studies provide the following evidence to help explain the mechanisms of lumbar facet pain: (1) The facet joint can carry a significant amount of the total compressive load on the spine when the human spine is hyperextended. (2) Extensive stretch of the human facet joint capsule occurs when the spine is in the physiologic range of extreme extension. (3) An extensive distribution of small nerve fibers and free and encapsulated nerve endings exists in the lumbar facet joint capsule, including nerves containing substance P, a putative neuromodulator of pain. (4) Low and high threshold mechanoreceptors fire when the facet joint capsule is stretched or is subject to localized compressive forces. (5) Sensitization and excitation of nerves in facet joint and surrounding muscle occur when the joint is inflamed or exposed to certain chemicals that are released during injury and inflammation. (6) Marked reduction in nerve activity occurs in facet tissue injected with hydrocortisone and lidocaine. Thus, the facet joint is a heavily innervated area that is subject to high stress and strain. The resulting tissue damage or inflammation is likely to cause release of chemicals irritating to the nerve endings in these joints, resulting in low back pain.
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PMID:Lumbar facet pain: biomechanics, neuroanatomy and neurophysiology. 887 68

Idiopathic low back pain has confounded health care practitioners for decades. The cellular and neural mechanisms that lead to facet pain, discogenic pain, and sciatica are not well understood. To help elucidate these mechanisms, anesthetized New Zealand white rabbits were used in a series of neurophysiologic and neuroanatomic studies. These studies showed the following evidence in support of facet pain: an extensive distribution of small nerve fibers and endings in the lumbar facet joint, nerves containing substance P, high threshold mechanoreceptors in the facet joint capsule, and sensitization and excitation of nerves in facet joint and surrounding muscle when the nerves were exposed to inflammatory or algesic chemicals. Evidence for pain of disc origin included an extensive distribution of small nerve fibers and free nerve endings in the superficial annulus of the disc and small fibers and free nerve endings in adjacent longitudinal ligaments. Possible mechanisms of sciatica included vigorous and long lasting excitatory discharges when dorsal root ganglia were subjected to moderate pressure, excitation of dorsal root fibers when the ganglia were exposed to autologous nucleus pulposus, and excitation and loss of nerve function in nerve roots exposed to phospholipase A2.
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PMID:Mechanisms of low back pain: a neurophysiologic and neuroanatomic study. 902 Feb 16

In a pilot study, the action of the 5-HT3 receptor antagonist, tropisetron, on different types of local rheumatic pain and inflammatory effects was studied. With intra-articular injection of tropisetron, an improvement in inflammation and pain was obtained in inflammatory rheumatic diseases and activated osteoarthrosis. Also, the majority of patients with localized soft-tissue rheumatic diseases (periarthritis) demonstrated an obvious decrease in their pain following local infiltration of tropisetron. Chronic low back pain and cervical pain responded somewhat to i.v. treatment with tropisetron. The effect of the 5-HT3 receptor antagonists is probable primarily to limit the release of substance P, which acts as a pain and inflammatory mediator, and is itself released by the neurogenic inflammation that occurs after the binding of serotonin to its corresponding receptor. These results should be backed up with placebo controlled studies, which if confirmed, might imply that 5-HT3 receptor antagonists could supplement or replace the local administration of corticosteroids.
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PMID:The use of 5-HT3 receptor antagonists in various rheumatic diseases--a clue to the mechanism of action of these agents in fibromyalgia? 1102 36


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