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)

In the awake restrained rat the intrathecal administration of substance P or the partial substance P homologue eledoisin-related peptide (ERP) reduced reaction time to a noxious radiant heat stimulus and, at high doses, produced additional behavioural responses suggesting that the animals had reacted to what they perceived as a painful stimulus. The reduction in tail-flick latency was observed as early as 30 sec following peptide administration peaked at 1 min and persisted for 5-10 min, after which an overshoot of the response (i.e., an increase in reaction time) was observed. The responses varied in their magnitude with the amount of peptide given, substance P being approximately 4 times more potent on a molar basis than ERP. Intrathecal administration of an equal volume of vehicle (artificial cerebrospinal fluid) had no effect on tail-flick latency and failed to produce any of the other behavioural changes. The following interpretations are made. The decrease in tail-flick latency suggests that pain threshold was decreased, and the dramatic behavioural effects seen at high doses suggest that an excess of substance P in the spinal cord is capable of producing a painful sensation. The rapid onset of the response suggests rapid penetration of substance P and ERP to the appropriate receptors, and the rapid decay of the response suggests rapid removal. Taken together, these results are consistent with the earlier suggestion that substance P plays a role as an excitatory agent in sensory pathways subserving pain. It is proposed that some conditions of chronic pain in man may therefore be due to an overabundant amount of substance P. This is complementary to a second proposal that other cases of chronic pain may be due to a supersensitivity of substance P receptors. The former is more likely to be associated with organic disorders, the latter with nerve damage, e.g. with causalgia, the neuralgias and perhaps some cases of phantom limb pain.
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PMID:Substance P reduces tail-flick latency: implications for chronic pain syndromes. 618 63

The experiments described in the present study approached nerve injury from both a biochemical and anatomical perspective by monitoring changes in expression of preprotachykinin (PPT) mRNA encoding the prototypic tachykinin substance P and related peptide species in neurons of the rat dorsal root ganglia (DRG) following unilateral chronic constriction injury of the sciatic nerve. In situ hybridization histochemistry (ISHH) analyses in conjunction with computer-assisted image processing were employed to quantify levels of PPT mRNA distributed in DRG neurons. Injury-induced changes in PPT mRNA expression by affected DRG neurons included: (1) at early postoperative times, generally increased levels of PPT mRNA associated with small and intermediate-size B cells exhibiting normal morphology, (2) at late postoperative times, markedly decreased levels of PPT mRNA associated with degenerating B cells, and (3) induction of PPT gene expression by large A cells which is highly correlated with degenerative morphological changes. The significant aspects of these changes are discussed with special emphasis on the contribution of altered transmitter expression by DRG neurons to the pathophysiology of causalgia. In particular, the induction of PPT gene expression by many of the large neurons undergoing degenerative changes may represent an important biochemical parameter which is associated with the development and persistence of experimental allodynia.
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PMID:Altered tachykinin expression by dorsal root ganglion neurons in a rat model of neuropathic pain. 781 89

From self-experimentation, I propose that the pain which occurs after application of capsaicin is causalgia and that this "capsaicin causalgia" is due to actual or functional depletion of neuropeptides such as substance P. This idea could provide an objective definition of the causalgic syndromes and improve the means of diagnosis. The analogy with capsaicin causalgia could also be extended to the pain of epidermal necrolysis, solar and thermal burns, and leprosy. The concept could lead to a better treatment of these causalgic syndromes by modulation of neuropeptide concentration or responsivity, or by mitigation of the consequences of its depletion.
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PMID:Capsaicin and the cause of causalgia. 771 53

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