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

The relation between electroacupuncture (EA) analgesia (A) and substance P (SP) level in the brain stem (BS) and lumbar spinal cord (LSC) of arthralgic rats was investigated. The rats were divided into three groups: 1)5.7-dihydroxytryptamine (5.7-DHT) + EA, 2) vehicle (V) + EA, and 3)5.7-DHT. All the animals were induced arthralgesia by injecting Freund's adjuvant 7 days after cisterna injection of 5.7-DHT or vehicle. The SP level in the BS and LSC was determined by RIA. The results indicated that in V + EA group the EA could prolong tail flick latency by 39.6%, but in other two groups did not. The SP level in LSC of V + EA group (179.1 +/- 11.5 pmol/g) was higher than that in the 5.7-DHT + EA (135.9 +/- 9.3pmol/g) and 5.7-DHT (125.8 +/- 10.0 pmol/g) groups. It suggested that both EA and arthralgia could activate the descending 5-HTergic inhibitory system to inhibit the release of SP in LSC. When the 5-HTergic system was destroyed by 5.7-DHT, the EAA was attenuated, and the SP level in LSC was lowered due to its release was decreased by EA and arthralgia.
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PMID:[Influence of 5.7-dihydroxytryptamine on electro-acupuncture analgesia and substance P level in central nervous system of the arthralgic rats]. 128 44

Joint pain is a common symptom in various forms of arthritis. Unfortunately, the mechanisms involved in the pathogenesis of joint pain are not well understood, but probably include peripheral and central neural mechanisms. The sympathetic system appears to interact with sensory afferents under pathological conditions, and this may be mediated directly via receptors on sensory neurons, or indirectly via inflammatory mediators. Classical inflammatory mediators such as serotonin and bradykinin appear to activate some nociceptive afferents and serotonin may sensitise these afferents to non-noxious stimuli in an inflamed joint. A purely sensory function has traditionally been ascribed to sensory afferents, but unmyelinated C fibres have in addition a neurosecretory role and release peptides such as substance P which may contribute to inflammation. Lastly, central sensitisation in the spinal cord may play an important role in the pathogenesis of joint pain. Activation of N-Methyl-D-Aspartate (NMDA) receptors and the wind-up phenomenon may be involved in central sensitisation.
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PMID:Neural mechanisms of joint pain. 750 3

Irrespective of the underlying mechanisms, joint pain usually originates in activation of nociceptors, or free nerve endings. Nociceptive signals release a large number of neuromediators, such as substance P and the calcitonin gene-related peptide. Complex neuronal activation occurs, which involves not only local sensitization of joint nociceptors but also modifications in central pain pathways. Additional complexity results from the ability of numerous environmental, psychological, and constitutional factors to influence joint pain.
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PMID:Pathophysiology of joint pain. 889 62

Cerebrospinal fluid (CSF) levels of substance P like immunoreactivity (SPLI) were determined in 11 patients with painful osteoarthritis in hip or knee, 9 patients with rhizopatic pain from a herniated lumbar disc, and in 9 healthy volunteers without pain. The patients with osteoarthritis had increased levels of SPLI in CSF (p < 0.001) compared to the controls. A positive correlation was also seen between the CSF SPLI and the degree of pain. At a second lumbar puncture 5 months after operation, SPLI had decreased, but was still significantly higher than in the controls. No difference in CSF SPLI was seen in the patients with herniated lumbar disc compared to the controls, neither before treatment, nor at follow up CSF postoperatively. The results suggest that nociceptive joint pain is consistent with increased SPLI in CSF. Differences in SPLI in CSF may be useful to differentiate pain from various origin, and may also increase our understanding of different pain mechanisms.
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PMID:Elevated cerebrospinal fluid substance P-like immunoreactivity in patients with painful osteoarthritis, but not in patients with rhizopatic pain from a herniated lumbar disc. 943 9

A 44-year-old woman with Marie-Bamberger's syndrome and diabetes insipidus had a lung tumour with mediastinal metastases, but no signs of metastases to the hypothalamus or pituitary gland. A week after removal of the tumour, the joint pain, polyuria and polydipsia disappeared. The tumour was diagnosed histopathologically as a moderately differentiated adenocarcinoma with focal neuroendocrine cell differentiation and dispersed cells reacting with antisera against neurone-specific enolase, S-100 protein, neuropeptide Y, follicle-stimulating hormone, substance P, vasoactive polypeptide (VIP), adrenocorticotropic hormone and pancreatic polypeptide (PP) as well as to one of three tested antisera raised against antidiuretic hormone (ADH). It was suggested that Marie-Bamberger's syndrome might be caused by one of these immunoreactive substances or by a substance that shares an amino acid sequence with one of these neuroendocrine peptides. It was also suggested that the tumour might produce an ADH-like substance which might have an ADH-antagonist effect.
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PMID:Recovery from Marie-Bamberger's syndrome and diabetes insipidus after removal of a lung adenocarcinoma with neuroendocrine features. 956 47

The substance P receptor neurokinin-1 is expressed by a subset of neurons in the rat spinal cord. We have combined immunostaining for Fos, a marker of noxious peripheral stimulation, and neurokinin-1 to examine whether nociceptive signals from particular peripheral tissues (skin, muscle or knee joint) or activity generated by nerve injury or formalin-induced inflammation are preferentially modulated by substance P. Our results indicate that superficial and deep spinal neurokinin-1-positive neurons process nociceptive information in markedly different ways. In lamina I, the number of double-labelled neurons was positively correlated with the intensity of the stimulus (defined by the total Fos count) and was not directly related to any particular peripheral target. However, in the deeper layers of the spinal cord (V-X), there was no such correlation, and stimulation of joint nociceptors and formalin-induced inflammation produced the greatest proportion of Fos/neurokinin-1 co-localization, suggesting a particular role for substance P in the mediation of joint pain and inflammatory hyperalgesia. Thus, lamina I neurokinin-1 receptor-bearing neurons appear to be involved in intensity discriminative aspects of pain, whereas the deep neurokinin-1 cells are involved in spatial localization or the detection of particular nociceptive submodalities.
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PMID:Substance P receptor (neurokinin-1)-expressing neurons in lamina I of the spinal cord encode for the intensity of noxious stimulation: a c-Fos study in rat. 1005 Dec 14

The role of the intra-articular synovial fold as a source of facet joint pain is unclear, because the nature of nociceptive innervation in lumbar synovial folds is controversial, and there have been no such studies in cervical synovial folds. The present study aimed to demonstrate the presence of nerve fibers including nociceptive fibers in synovial folds of human cervical facet joints using immunohistochemistry. Synovial folds of cervical facet joints removed from patients undergoing cervical spine laminoplasty were analyzed immunohistochemically using antibodies to protein gene product 9.5, beta III-tubulin, substance P and calcitonin gene-related peptide. Many nerve fibers immunoreactive for protein gene product 9.5 and beta III-tubulin were demonstrated both around blood vessels and as free fibers in the stroma of the synovial fold. Also. immunostaining showed the presence of free nerve fibers immunoreactive for substance P and calcitonin gene-related peptide in the stroma. The presence of putative nociceptive fibers in cervical synovial folds supports a possible role for these structures as a source of cervical facet joint pain.
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PMID:Immunohistochemical demonstration of nerve fibers in the synovial fold of the human cervical facet joint. 1151 67

Both the analgesic drugs tramadol and paracetamol are widely used for the symptomatic therapy of osteoarthritis (OA). The aim of this double-blind, randomised study in patients with knee OA was to compare their effects on synovial fluid concentrations of interleukin (IL)-6 and substance P (SP). Moreover, we evaluated plasma and synovial fluid concentrations of tramadol and its active metabolite (O-desmethyl-tramadol, M1) after oral treatment with this drug. Twenty patients were enrolled. A group of 10 patients received tramadol (50 mg three times a day), and another group of 10 patients were treated with paracetamol (500 mg three times a day) for 7 days. Both drugs significantly reduced the intensity of joint pain. The synovial fluid concentrations of SP were significantly reduced only by the treatment with tramadol. In this group of patients, IL-6 synovial fluid concentrations were slightly, but not significantly, decreased. Paracetamol did not significantly change the synovial fluid concentrations of SP and IL-6. After oral administration, a considerable amount of tramadol was measurable in synovial fluid. Both in plasma and synovial fluid the concentrations of M1 were markedly lower than those of tramadol, with a T/M1 ratio of 14.7+/-4.6 and 9.3+/-3.9, respectively. These data demonstrate that the activity of tramadol may involve the modulation of inflammatory mediators. Moreover, they indicate that after oral treatment with tramadol, both the parent drug and its active metabolite can penetrate into synovial fluid.
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PMID:Effects of tramadol on synovial fluid concentrations of substance P and interleukin-6 in patients with knee osteoarthritis: comparison with paracetamol. 1463 39

Characterization and differentiation of joint pain is difficult. Though degenerative changes in joints are frequent causes of pain in hip and knee, these changes are not always painful, and other possible causes of pain must also be considered. In degenerative changes in the spine, the problem is even more complex, as peripheral neuropathic pain, caused by mechanical compression and/or leakage of cytokines irritating nerve roots may be difficult to differentiate from nociceptive pain from intervertebral joints, discs or muscles. We know now that nociceptive pain has often referred to areas of pain with numbness and parestesthethic sensations, previously regarded as characteristic for neurogenic pain. Furthermore, in patients with painful coxarthrosis quantitative sensory testing (QST) has shown disturbed sensory thresholds not only in regions adjacent to the affected hip but also contralaterally. These sensory disturbances, previously noted in neuropathic pain, normalized after successful surgery with relief of pain, thus confirming the relation to the hip joint. Patients with painful coxarthrosis also have moderately increased substance P activity in cerebrospinal fluid. Thus the findings show some similarities with fibromyalgic patients with highly increased substance P in cerebrospinal fluid and sensory disturbances. In conclusion, joint pain has a profound impact on the sensory system and need a multimodal approach.
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PMID:Characterization of joint pain in human OA. 1528 46

Innervation of the joint with thinly myelinated and unmyelinated sensory nerve fibres is crucial for the occurrence of joint pain. During inflammation in the joint, sensory fibres show changes in the expression of receptors that are important for the activation and sensitization of the neurones and the generation of joint pain. We recently reported that both neurokinin 1 receptors and bradykinin 2 receptors are upregulated in dorsal root ganglion (DRG) neurones (the cell bodies of sensory fibres) in the course of acute and chronic antigen-induced arthritis in the rat. In this study, we begin to address mechanisms of the interaction between fibroblast-like synovial (FLS) cells and sensory neurones by establishing a co-culture system of FLS cells and DRG neurones. The proportion of DRG neurones expressing neurokinin 1 receptor-like immunoreactivity was not altered in the co-culture with FLS cells from normal joints but was significantly upregulated using FLS cells from knee joints of rats with antigen-induced arthritis. The proportion of DRG neurones expressing bradykinin 2 receptors was slightly upregulated in the presence of FLS cells from normal joints but upregulation was more pronounced in DRG neurones co-cultured with FLS cells from acutely inflamed joints. In addition, the expression of the transient receptor potential V1 (TRPV1) receptor, which is involved in inflammation-evoked thermal hyperalgesia, was mainly upregulated by co-culturing DRG neurones with FLS cells from chronically inflamed joints. Upregulation of neurokinin 1 receptors but not of bradykinin 2 and TRPV1 receptors was also observed when only the supernatant of FLS cells from acutely inflamed joint was added to DRG neurones. Addition of indomethacin to co-cultures inhibited the effect of FLS cells from acutely inflamed joints on neurokinin 1 receptor expression, suggesting an important role for prostaglandins. Collectively, these data show that FLS cells are able to induce an upregulation of pain-related receptors in sensory neurones and, thus, they could contribute to the generation of joint pain. Importantly, the influence of FLS cells on DRG neurones is dependent on their state of activity, and soluble factors as well as direct cellular contacts are crucial for their interaction with neurones.
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PMID:Fibroblast-like synovial cells from normal and inflamed knee joints differently affect the expression of pain-related receptors in sensory neurones: a co-culture study. 1725 43


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