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 contribution of the nervous system to the pathophysiology of rheumatoid arthritis has been proposed to be mediated by certain neuropeptides. Neuropeptide Y, calcitonin gene-related peptide, substance P, and neurokinin A are considered modulators of inflammatory joint disease. Parameters of pain, as well as occlusal signs of tissue destruction from the arthritic TMJ and the corresponding neuropeptide concentrations in TMJ synovial fluid, were investigated in patients with various inflammatory joint diseases. The patients with rheumatoid arthritis were also examined in a separate diagnostic group. Visual analog scale, palpatory tenderness, maximal voluntary mouth opening, and anterior open bite were correlated to neuropeptide-like immunoreactivities of the above four neuropeptides. It was found that high concentrations of calcitonin gene-related peptide and neuropeptide Y in TMJ fluid are associated with pain, impairment of mandibular mobility, and occlusal signs of TMJ destruction in patients with rheumatoid arthritis. The results indicated neuropeptide involvement in rheumatoid arthritis, proposing a potentiation of the symptoms and signs by the inflammatory action of calcitonin gene-related peptide and neuropeptide Y.
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PMID:Neuropeptides in the arthritic TMJ and symptoms and signs from the stomatognathic system with special consideration to rheumatoid arthritis. 899 21

We have investigated the effect of capsaicin pretreatment (50 mg kg(-1) s.c.) on substance P, preprotachykinin (PPT) mRNA, and nerve growth factor (NGF), plus its high-affinity receptor, trkA, in adult rats with adjuvant arthritis. Twenty one days after induction of adjuvant arthritis, sciatic nerve levels of substance P were significantly increased whilst there was a small but non-significant increase in gamma-PPT mRNA and substance P in L4/L5 dorsal root ganglia (DRG). NGF levels in sciatic nerve and foot skin as well as DRG trkA mRNA were unaltered after 21 days arthritis suggesting that NGF may not play a role in chronic inflammation. Capsaicin treatment of naive rats significantly reduced substance P in all tissues and NGF levels in the sciatic nerve. In contrast, gamma-PPT mRNA and trkA mRNA expression in DRG were significantly increased after capsaicin treatment. The nervous and skin tissues used in this study were harvested from the same rats in which we had previously shown that capsaicin pretreatment significantly attenuated the severity of arthritis (Cruwys, S.C., Garrett, N.E. and Kidd, B.L., Sensory denervation with capsaicin attenuates inflammation and nociception in arthritic rats, Neurosci. Lett., 193 (1995) 205-207). Arthritis in capsaicin-treated rats had no effect on substance P or NGF levels in any tissue when compared with capsaicin-treated control rats, suggesting that pharmacological impairment of the sensory nervous system can reduce the severity of inflammatory joint disease.
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PMID:Effect of capsaicin on substance P and nerve growth factor in adjuvant arthritic rats. 925 50

Neuropeptides are considered mediators and modulators of inflammatory joint disease. Substance P (SP) has been proposed as a mediator of pain, and its vasoactive properties are well documented. In this study, the presence of SP-like immunoreactivity in the synovial fluid was correlated to intra-articular temperature (IAT) and pain from the arthritic temporomandibular joint (TMJ) 3 to 5 weeks after one intra-articular injection of glucocorticosteroids. Eighteen TMJs were investigated for IAT and the presence of SP-like immunoreactivity in the synovial fluid in 12 patients with systemic inflammatory joint disease. After arthrocentesis, the aspirates were analyzed for SP-like immunoreactivity by means of competitive radio immunoassay. A visual analogue scale and an algometer determining the pressure pain threshold and tolerance level assessed arthritic pain and hyperalgesia in the TMJ. Our results indicate that SP-like immunoreactivity is associated with IAT and that increased concentrations of joint fluid SP-like immunoreactivity correspond to increased pain threshold and tolerance and a concomitantly decreased visual analogue scale. These findings suggest that SP is implicated in the vascular and nociceptive response of the arthritic joint and that SP, possibly assisted by the antinociceptive effect of local corticosteroids, has a modulatory role in arthritic pain and hyperalgesia.
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PMID:Substance P-associated increase of intra-articular temperature and pain threshold in the arthritic TMJ. 965 87

We have previously shown that kappa-opioids have antiarthritic properties. In this study, using two differently acting drugs (the peripherally selective kappa-agonist, asimadoline, and the NK1-antagonist, GR205171), we have examined possible roles of the neuropeptide substance P (SP) in the pathogenesis and maintenance of experimental arthritis in rats. The anti-inflammatory actions and the time dependence of these drugs were compared, and concentrations of SP determined in joint tissue. In untreated animals, SP levels in ankle joint tissue increased late in the disease (by day 21) but substantially lagged behind development of clinical disease. Prolonged (days 1-21 or days 12-18) but not early, short-term (days 1-3) treatment with the NK1-antagonist GR205171 (1 mg/kg/day i.p.) significantly attenuated joint damage; SP levels showed multiphasic dose dependence over the 21-day treatment. The data suggest that GR205171 antagonizes the action of SP by presynaptic as well as postsynaptic mechanisms. Treatment with asimadoline (5 mg/kg/day i.p. ) produced marked (and sustained) attenuation of the disease with all three time regimes. The effect of asimadoline on SP levels was time dependent: reduction of SP content after 3 days but an increase after 12 or 21 days treatment, paradoxically with clinical improvement in each case. Drug-induced changes in SP content could follow from changed release or synthesis from either neural or immune cells. The results suggest that both drugs have potential therapeutic value at different stages of inflammatory joint disease.
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PMID:Involvement of substance P in the anti-inflammatory effects of the peripherally selective kappa-opioid asimadoline and the NK1 antagonist GR205171. 1033 75

The activation of a cellular immune response in a genetically susceptible individual is widely recognised as a main step in triggering rheumatoid arthritis (RA). The tachykinins, substance P (SP) and neurokinin A (NKA), can play a major role in different immune diseases. In patients with inflammatory joint disease, elevated levels of SP have been demonstrated in the synovial fluid of affected joints. It is well known that SP and, to a lesser extent, NKA are deeply involved in the processing of nociceptive signals and exert many pro-inflammatory actions, which may be elicited by an increased neuronal neurokinin release in arthritis; the mechanism behind this increase remains to be fully elucidated. Different observations suggest that one approach to the treatment of RA might be to inhibit the local effects of neurokinins in the affected joints. This review will summarise the more relevant aspects of this topic.
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PMID:Tachykinin receptor modulators: novel therapeutics for rheumatoid arthritis. 1113 31


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