Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Sciatic section in rats evokes chronic hyperalgesia, autotomy pain behavior, and hindpaw edema, a constellation resembling complex regional pain syndrome (CRPS) in man. Glucocorticoid treatment inhibits these sequelae of sciatic section and also blocks neurogenic extravasation. Small diameter afferent neurons release substance P (SP), a mediator of both hyperalgesia and neurogenic extravasation. Now, we show that pre-emptive destruction of the small diameter fibers prevents neurogenic extravasation, and prevented the development of heat hyperalgesia and hindpaw edema after sciatic section. Thus, capsaicin sensitive primary afferent neurons which release SP are required for the development of heat hyperalgesia and hindpaw edema in this animal model of CRPS.
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PMID:Capsaicin sensitive afferents mediate the development of heat hyperalgesia and hindpaw edema after sciatic section in rats. 1178 20

Neurogenic inflammation is elicited by activation of unmyelinated sensory neurons through noxious stimuli and subsequent release of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) from peripheral nerve endings. The nerve-mediated inflammatory responses in the tissue consist of hyperaemia and oedema which under some circumstances may be accompanied by pain. Neurogenic inflammation has been implicated in the pathophysiology of various human diseases with uncertain etiology. Signs of inflammation and hyperalgesia associated with chronic pain syndromes such as migraine, arthritis and complex regional pain syndrome resemble the characteristics of neurogenic inflammation. By extrapolation of convincing evidence obtained in rodent models, neurogenic inflammation is assumed to contribute to diseases of the respiratory system, gastrointestinal tract, urogenital tract, and skin in humans. Since, however, highly selective substance P receptor antagonists, found to be effective against inflammation in rodents, failed to inhibit inflammatory processes in clinical trials, the hypothesis of an involvement of neurogenic inflammation in human diseases is discussed critically in this review. Beyond its primarily inflammatory character neurogenic inflammation can be regarded as a mechanism that activates protective responses, thus bringing about a first line of defence to maintain the integrity of the tissue and to contribute to tissue repair.
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PMID:[Neurogenic inflammation. II. pathophysiology and clinical implications]. 1210 11

Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of beta-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-alpha and interleukin-10 are discussed.
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PMID:Anti-inflammatory actions of acupuncture. 1277 55

Sciatic nerve section in rats evokes chronic hindlimb edema, pain behavior, and hyperalgesia, a syndrome resembling complex regional pain syndrome (CRPS II) in man. Furthermore, there is an increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous limbs of CRPS patients. Now we demonstrate that sciatic nerve section also generates chronic hindlimb warmth, distal articular tenderness, allodynia, and periarticular osteoporosis, sequelae of nerve injury resembling those observed in CRPS. We postulated that facilitated substance P signaling may contribute to these vascular and nociceptive abnormalities and attempted to reverse these changes with the long acting substance P receptor (NK(1)) antagonist LY303870. Hindpaw spontaneous extravasation was inhibited by LY303870. Systemic administration of LY303870 also reversed hindpaw edema and cutaneous warmth. Intrathecal, but not systemic administration of LY303870 reversed soft tissue and articular mechanical hyperalgesia in the hindpaw. Collectively, these data further support the hypothesis that the sciatic nerve transection model closely resembles CRPS and that substance P contributes to the spontaneous extravasation, edema, warmth, and mechanical hyperalgesia observed in this model.
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PMID:A substance P receptor (NK1) antagonist can reverse vascular and nociceptive abnormalities in a rat model of complex regional pain syndrome type II. 1285 16

Pain, mechanical hyperalgesia, edema, increased skin temperature, and skin reddening are characteristic symptoms of acute complex regional pain syndrome (CRPS). We have recently demonstrated facilitated neurogenic inflammation on the affected limb. To further elucidate the underlying mechanisms, exogenous substance P (SP) in ascending concentrations (10(-9), 10(-8), 10(-7), 10(-6) M) was intradermally applied to the affected and the unaffected limbs, respectively, in two groups of 11 CRPS patients each using the microdialysis technique. Fourteen healthy volunteers served as controls for SP application, and 9 volunteers and 10 patients served as controls for saline perfusion. Dialysate protein content was measured photometrically to assess plasma protein extravasation. Significant differences in dialysate protein content were found after 10(-9) M SP (affected side, 98.4 +/- 8.4% of baseline value; unaffected side, 104.4 +/- 5.6%; controls, 70.7 +/- 4.1%; P < 0.005) and after 10(-6) M SP (affected, 169.7 +/- 24.2%; unaffected, 189.4 +/- 19.1%; controls, 122.2 +/- 12.0%; P < 0.05). While 10(-9) M SP induced no protein extravasation in controls, it provoked protein extravasation in 6 of 11 patients on the affected and in 5 of 11 patients on the unaffected side (P < 0.01). We conclude that SP-induced plasma protein extravasation is increased in CRPS patients on both the affected and unaffected limbs. The underlying mechanism might be impaired SP inactivation. Thus, our results further support the hypothesis that neurogenic inflammation plays an important role in the initiation of CRPS.
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PMID:Substance-P-induced protein extravasation is bilaterally increased in complex regional pain syndrome. 1295 2

Wrist and ankle fractures are the most frequent causes of complex regional pain syndrome (CRPS type I). The current study examined the temporal development of vascular, nociceptive and bony changes after distal tibial fracture in rats and compared these changes to those observed after cast immobilization in intact normal rats. After baseline testing the right distal tibial was fractured and the hindlimb casted. A control group was simply casted without fracturing the tibia. After 4 weeks the casts were removed and the rats retested. Subsequent testing was performed at 6, 8, 10, 16, and 20 weeks after onset of treatment. Distal tibial fracture or cast immobilization alone generated chronic hindlimb warmth, edema, spontaneous protein extravasation, allodynia, and periarticular osteoporosis, changes resembling those observed in CRPS. Hindlimb warmth and allodynia resolved much more quickly after cast immobilization than after fracture. Previously we observed that the substance P receptor (NK(1)) antagonist LY303870 reversed vascular and nociceptive changes in a sciatic section rat model of CRPS type II. Postulating that facilitated substance P signaling may also contribute to the vascular and nociceptive abnormalities observed after tibial fracture or cast immobilization, we attempted to reverse these changes with LY303870. Hindpaw warmth, spontaneous extravasation, edema, and allodynia were inhibited by LY303870. Collectively, these data support the hypotheses that the distal tibial fracture model simulates CRPS, immobilization alone can generate a syndrome resembling CRPS, and substance P signaling contributes to the vascular and nociceptive changes observed in these models.
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PMID:Substance P signaling contributes to the vascular and nociceptive abnormalities observed in a tibial fracture rat model of complex regional pain syndrome type I. 1510 12

Tibia fracture in rats evokes chronic hindpaw warmth, spontaneous extravasation, edema, allodynia, and periarticular bone loss, a syndrome resembling complex regional pain syndrome type I (CRPS I). Glucocorticoids such as methylprednisolone (MP) are probably effective analgesic and anti-edematous agents in patients suffering from CRPS and this study examined the effects of chronic MP treatment in the rat CRPS I model. Bilateral hindpaw thickness, temperature, and nociceptive thresholds were determined, and the hindlimb bone density was measured using dual-energy X-ray absorptiometry (DXA). Spontaneous cutaneous extravasation and substance P infusion evoked extravasation were determined using an Evans blue vascular permeability assay. After baseline testing, the distal tibia was fractured and the hindlimb casted for 4 weeks. At 2 weeks post-fracture MP infusion was started (1 mg/kg/day for 28 days). The rats were retested at 4, 6, and 8 weeks post-fracture. Hindpaw edema and warmth after fracture were reversed by MP infusion and these effects persisted after discontinuing treatment. Furthermore, there was an increase in spontaneous protein extravasation and an enhanced substance P evoked extravasation and edema response in the hindpaw at 4 weeks that was inhibited by MP infusion. Glucocorticoid treatment had no effect on the allodynia, hindpaw unweighting, or the periarticular bone loss observed after tibia fracture. We postulate that post-junctional facilitation of substance P signaling contributes to the hindpaw warmth, edema, and the enhanced spontaneous protein extravasation observed in this CRPS I model, and that the anti-edematous effects of glucocorticoid treatment are due to inhibition of post-junctional neuropeptide signaling.
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PMID:Glucocorticoid inhibition of vascular abnormalities in a tibia fracture rat model of complex regional pain syndrome type I. 1647 17

The tachykinin family of vasoactive peptides comprises the neuropeptides substance P, neurokinin A and neurokinin B, and the newly discovered endokinins and hemokinins. Their cardiovascular effects are predominantly mediated by the family of neurokinin receptors. This review summarises the most recent advances in understanding the effects of tachykinins on the vasculature, and summarises their therapeutic potential. Tachykinins stimulate plasma extravasation, particularly acting through neurokinin-1 receptors in an endothelium-dependent manner. They therefore play prominent roles in tissue oedema and inflammation (called neurogenic inflammation). Pro-inflammatory effects of tachykinins are enhanced by their capacity to stimulate inflammatory cell recruitment, and to initiate angiogenesis. Tachykinins also regulate vascular tone and blood flow, although differences between species and between different vascular beds make this a highly complex area of research. They may relax vessels in some scenarios whilst inducing vasoconstriction in other situations, the state of the endothelium appearing to be of key importance. Tachykinins also modulate blood pressure and heart rate, acting both peripherally, and on the central nervous system. Cardiovascular effects of tachykinins and neurokinin receptors may be important therapeutic targets in diverse disorders such as pulmonary oedema, hypertension, pre-eclampsia, complex regional pain syndrome type 2, stroke and chronic inflammatory diseases such as arthritis. Sophisticated modelling of human disease is required to enable neurokinin receptor antagonists to achieve this therapeutic potential.
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PMID:Tachykinins and the cardiovascular system. 1691 31

Substance P is involved in nociception in both the peripheral nervous system and the CNS and has been documented to play a crucial role in the complex regional pain syndrome (CRPS). So far, however, most experimental animal models are restricted to the effect of neurokinin-1 receptor blockers to inhibit substance P and do not directly evaluate its action. Thus, this study was conducted to test the hypothesis that local application of substance P causes signs and symptoms of CRPS. For this purpose rats received a continuous infusion of either substance P or saline over 24 h delivered by a mini-osmotic pump connected to an intrafemoral catheter. Animals were analyzed at either day 1 (n=6, each group) or day 4 (n=5, each group) after start of infusion. Substance P application caused a significant and long-lasting decrease in paw withdrawal thresholds upon mechanical stimulation, while animals did not present with thermal allodynia at days 1 and 4 after onset of infusion. In addition, severe s.c. edema was observed in all animals receiving substance P. In vivo fluorescence microscopy of the extensor digitorum longus muscle of the affected hind paw revealed enhanced leukocyte-endothelial cell interaction with a significant rise in the number of leukocytes both rolling along and firmly adhering to the wall of postcapillary venules, while saline-exposed animals were free of this local inflammatory response. Muscle cell apoptosis, as assessed by in vivo bisbenzimide staining, terminal deoxynucleotidyl transferase nick end labeling analysis and caspase 3-cleavage, could not be observed in either of the animals. In summary, the present study indicates that substance P is responsible for neurogenic inflammation, including local cell response, edema formation and mechanical pain, while it seems not to contribute to the generation of thermal allodynia.
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PMID:Continuous intra-arterial application of substance P induces signs and symptoms of experimental complex regional pain syndrome (CRPS) such as edema, inflammation and mechanical pain but no thermal pain. 1768 87

Changed vascular functions have been reported in several pathological conditions, such as chronic regional pain syndrome, obstructive vascular disease, and inflammation. Our previous experiments also showed that electrical stimulation of the lumbar sympathetic trunk (sympathetic stimulation: SS), which normally induces a decrease in blood flow (BF), caused a BF increase in about half of the measured sites in rats persistently inflamed with complete Freund's Adjuvant (AI rats). We also showed that the BF-increase response was only partially suppressed by the alpha1 antagonist at a higher dosage, suggesting the involvement of nonadrenergic mechanisms. We hypothesize that nonadrenergic mechanisms mediating vasodilatation might involve a vasodilating neuropeptide such as substance P (SP) that is released from sympathetic nerve terminals. In this experiment, we conducted an examination using an NK-1 receptor antagonist to determine whether SP plays any role in changed response to SS in AI rats, and also an immunohistochemical examination of whether SP is expressed in the lumbar sympathetic nerve ganglia (SG) of AI rats. The administration of an NK-1 receptor antagonist, CP-96,345, significantly reduced the BF-increase response to SS in AI rats, but its inactive enantiomer, CP-96,344, had no effect. Immunohistochemistry for SP revealed that SP-ir positive SG neurons (mean 13 neurons/rat) were found in 5 of 8 AI rats, whereas only one neuron was stained in 8 control rats. These results suggest that NK-1 receptor activation is involved in the BF-increase response to SS, and that this activation is in part mediated by SP from lumbar SG that was synthesized de novo in inflamed animals.
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PMID:Substance P is involved in the cutaneous blood flow increase response to sympathetic nerve stimulation in persistently inflamed rats. 1805 15


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