Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the participation of cyclin-dependent kinase-5 (Cdk5)-mediated N-methyl-D-aspartate receptor (NMDAR) NR2B subunit phosphorylation in cross-organ reflex sensitization caused by colon irritation. The external urethral sphincter electromyogram (EUSE) reflex activity evoked by the pelvic afferent nerve test stimulation (TS, 1 stimulation/30s) and protein expression in the spinal cord and dorsal root ganglion tissue (T13-L2 and L6-S2 ipsilateral to the stimulation) in response to colon mustard oil (MO) instillation were tested in anesthetized rats. When compared with a baseline reflex activity with a single action potential evoked by the TS before the administration of test agents, MO instillation into the descending colon sensitized the evoked activity characterized by elongated firing in the reflex activity in association with increased protein levels of Cdk5, PSD95, and phosphorylated NR2B (pNR2B) but not of total NR2B (tNR2B) in the spinal cord tissue. Both cross-organ reflex sensitization and increments in protein expression were reversed by intra-colonic pretreatments with ruthenium red (a non-selective transient receptor potential vanilloid, TRPV, antagonist), capsaizepine (a TRPV1-selective antagonist), lidocaine (a nerve conduction blocker) as well as by the intra-thecal pretreatment with APV (a NRMDR antagonist) Co-101244 (a NR2B-selective antagonist) and roscovitine (a Cdk5 antagonist). Moreover, compared with the control group, both the increase in pNR2B and the cross-organ reflex sensitization were attenuated in the si-RNA of NR2B rats. All these results suggested that Cdk-dependent NMDAR NR2B subunit phosphorylation mediates the development of cross-organ pelvic-urethra reflex sensitization caused by acute colon irritation which could possibly underlie the high concurrence of pelvic pain syndrome with irritable bowel syndrome.
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PMID:Colon mustard oil instillation induced cross-organ reflex sensitization on the pelvic-urethra reflex activity in rats. 1916 22

Patients with irritable bowel syndrome suffer from chronic visceral pain, and in some of them, this is accompanied by anxiety comorbidity. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the cytoplasmic polyadenylation of mRNAs and facilitates their translation. Our previous studies have shown that CPEB1 knockdown in the amygdala exerts anxiolytic but not analgesic effects in a mouse model of inflammatory pain. However, the roles of CPEB1 in the anterior cingulate cortex (ACC) in visceral pain modulation remain unclear. In this study, a visceral pain mouse model was established by injecting zymosan into the colon of mice. Zymosan injection significantly induced visceral pain- and anxiety-like behaviors in mice and increased the levels of GluA1, phosphorylated GluA1 at S845 and S831, and CPEB1 in the ACC. CPEB1 knockdown in the ACC by AAV-CPEB1-shRNA reduced zymosan-induced pain- and anxiety-like behaviors in mice. This observation was closely correlated with reduced AMPA receptor, synaptophysin, and PSD95 levels. These data suggest that CPEB1 in the ACC is a potential therapeutic target for visceral pain and anxiety comorbidity.
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PMID:Effects of CPEB1 in the anterior cingulate cortex on visceral pain in mice. 3073 Oct 77