Changes in urinary bladder smooth muscle function in response to colonic inflammation

Abstract

Visceral organ "cross talk" is suspected to contribute to multiorgan symptomatology found in conditions such as irritable bowel syndrome and interstitial cystitis. The goal of the present study was to investigate the short- and long-term effects of acute colitis on bladder detrusor muscle contractility. We hypothesized that inflammation of the colon leads to changes in bladder function via direct changes in detrusor smooth muscle contractility. In this study, colonic inflammation was induced in male rats via an enema of trinitrobenzenesulfonic acid (TNBS) (50 mg/kg, 0.5 ml, 25% ethanol). Colitis was confirmed using gross morphology, histology, and measurements of myeloperoxidase activity. Saline enema-treated rats served as controls. Three, 15, and 30 days postenema treatment, bladder detrusor muscle contractility was investigated in response to electrical field stimulation (EFS), cholinergic agonism with carbachol (CCh), and KCl. During active colonic inflammation (day 3 post-TNBS enema), the bladder detrusor muscle appeared normal and showed no significant inflammation. However, abnormalities in bladder detrusor muscle contractility occurred in response to EFS and CCh but not KCl. During and after recovery from colonic inflammation (days 15 and 30 post-TNBS enema), changes in bladder detrusor muscle contractility in response to EFS and CCh returned to control levels. We found that a transient colonic inflammatory insult significantly attenuates the amplitude of bladder detrusor muscle contractions in vitro, at least in part, through changes in cholinergic innervation, which are reversible after recovery from the colitis.

Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization

“…The reduction in bladder detrusor muscle contractility in response to CCh during TNBS-induced active colonic inflammation suggests that alterations in cholinergic neurotransmission occur within the bladder detrusor muscle. The same study (32) observed a reduction in the detrusor response to high-frequency EFS (16 and 32 Hz), whereas we did not reach statistical significance in our experiments. We believe this discrepancy in findings could be because of some differences in methodological approaches, including a lower concentration of TNBS used for the induction of colonic inflammation in our experiments and application of only a single frequency of 32 Hz, which stimulated the maximal release of neuropeptides from nerve terminals.…”

“…These data are consistent with previously published results that showed a reduced response of the detrusor muscle to CCh after acute experimental colitis without changes upon stimulation by KCl (32). The reduction in bladder detrusor muscle contractility in response to CCh during TNBS-induced active colonic inflammation suggests that alterations in cholinergic neurotransmission occur within the bladder detrusor muscle.…”

“…Isometric contractions were studied in response to EFS at 32 Hz. This frequency was chosen based on our previous studies that showed the alterations in detrusor contractility at higher frequencies (32). Acute colonic inflammation (TNBS group) did not lead to significant changes in detrusor contractility after EFS.…”

“…Previous animal studies have established a correlation between structural pathophysiological changes in the directly affected pelvic organs and secondary dysfunctions developed in adjacent pelvic structures (9,27,28,36). It has been determined that colonic inflammation causes hyperactivity of bladder afferent fibers (44), hyperexcitability of bladder projecting sensory (27,28) and spinal (38) neurons, increased release of proinflammatory neuropeptides in the urinary bladder (34,45), and changes in the detrusor contractility (32). However, the exact pathways of transmission of nociceptive information from the inflamed colon to the urinary bladder as well as receptors and molecules activated during this transmission remain elusive.…”

The effect of spinal cord injury on vagal afferents.

“…For instance, numerous studies in experimental models of different species and in clinical reports (Whorwell et al, 1986a, Whorwell et al, 1986b, Alagiri et al, 1997 demonstrate physiological evidence of cross-organ sensitization between both organs, including effects such as increased urinary frequency, urgency, nocturia, abnormal bladder detrusor muscle contractility and emptying or increased responses to colonic distention at lower than normal pressures (Floyd 27 et al, 1978, Bouvier et al, 1990, Malykhina et al, 2004, Pezzone et al, 2005, Qin et al, 2005, Bielefeldt et al, 2006a, Lamb et al, 2006, Malykhina et al, 2006, Ustinova et al, 2006, Noronha et al, 2007, Qiao and Grider, 2007, Rudick et al, 2007, Ustinova et al, 2010, Lei and Malykhina, 2012, Lei et al, 2013. It is important to note that convergence through both spinal and/or vagal afferents occurs centrally as well.…”