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)

Chronic pelvic pain afflicts some 9,000,000 women in the United States. Of these, perhaps 10%-although the true number of those affected is actually much greater-are found to have interstitial cystitis (IC), that is, pain of bladder origin. The etiology is multifactorial, but a fairly good marker is dysfunction of the glycosaminoglycan/mucus/mucin layer of the bladder as detected by a potassium (KCl) sensitivity test. A cascade starting with Substance P seems to be involved in generating inflammation, and even ulceration, which is the focus of pain. This article describes means of diagnosis, including the KCl test and cystoscopy, and both U.S. FDA-approved and extended-use medical treatment options which are always to be attempted before the final step of surgery.
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PMID:Chronic pelvic pain of bladder origin: a focus on interstitial cystitis. 1367 48

Chronic pelvic pain (CPP) disorders frequently overlap. We have demonstrated that acute and chronic colonic irritation can lead to neurogenic cystitis. We hypothesize that acute colonic irritation can sensitize urinary bladder afferents to mechanical and chemical stimuli. Single-unit afferent activity was recorded from fine filaments of the pelvic nerve in urethane-anesthetized Sprague-Dawley female rats before and 1 h after intracolonic administration of trinitrobenzenesulfonic acid (TNBS). Only spontaneously active afferents with receptive fields in the bladder and conduction velocities <2.5 m/s (unmyelinated C-fibers) were studied. Mechanical sensitivity was tested by bladder distension (BD) during saline infusion, whereas chemical sensitivity was tested with intravesical capsaicin, bradykinin, or substance P. Colonic irritation increased the resting firing rate of bladder afferents twofold (1.0 +/- 0.2 vs. 0.49 +/- 0.2 impulses/s, P < 0.05). Moreover, at low-pressure BDs (10-20 mmHg), a greater percentage of afferents exhibited increased activity following TNBS (73 vs. 27%, P < 0.05). Although the magnitude of the afferent response to BD was unchanged at low pressures, the response was greatly enhanced at pressures 30 mmHg and above (2.36 +/- 0.56 vs. 8.55 +/- 0.73 impulses/s, P < 0.05). Responses to capsaicin, bradykinin, and substance P were also significantly enhanced following TNBS, and all responses were blocked by bladder denervation. In rats, colonic irritation sensitizes urinary bladder afferents to noxious mechanical and chemical stimuli. Interruption of the neural input to the bladder minimized this effect, suggesting a local afferent pathway from the colon. Thus, the overlap of CPP disorders may be a consequence of pelvic afferent cross-sensitization.
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PMID:Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization. 1640 32