The Loss and Progressive Recovery of Voiding after Spinal Cord Interruption in Rats is Associated with Simultaneous Changes in Autonomous Contractile Bladder Activity

Abstract

Background: Autonomous contractile activity (ACA) is a well-known phenomenon in isolated bladders from different species and seems to be important in the physiology of both normal and dysfunctional voiding. Objective: To determine whether ACA is changed in bladders from paraplegic rats at different periods post-spinal cord injury (post-SCI). Design, setting, and participants: ACA was studied in bladders (at least six per group) from normal and paraplegic female Wister rats at different times post-SCI (2 h, 24 h, 1 wk, and 3 wk). A group of normal rats was used as a control group. For measurements bladders were incubated in organ baths under standardised conditions. Measurements: ACA was measured as pressure change, which was defined as either a transient change or a spiked change according to its characteristics. The effects of intravesical volume load and muscarinic agonists were studied. Results and limitations: Following spinal cord injury (SCI) a clear evolution in ACA was observed. In bladders from SCI rats in the acute areflexive voiding phase (1 wk post-SCI), we observed decreased ACA associated with a highly increased compliance and a changed response to muscarinic agonists. ACA in bladders from SCI rats with renewed voiding reflexes (3 wk post-SCI) was increased, together with a moderately increased compliance and a (moderately) changed response to muscarinic agonists. Conclusions: From these observations it is apparent that SCI leads to alterations in the behaviour and muscarinic response of ACA in the isolated bladder. These changes in ACA may play an important role in the pathophysiology of overactive bladder disease (OAB), and interacting with changed ACA might be promising in the search for newer treatments for OAB.

The impact of discrete modes of spinal cord injury on bladder muscle contractility

“…Although cholinergic contractile responses are normally mediated by the M3 muscarinic receptor subtype, alterations in M2 receptor signaling in smooth muscle have been reported post-SCI. In the rat, SCI enhanced the response to a M2 receptor agonist and increased M2 receptor gene expression [18], suggesting an augmented contribution from M2 receptor signaling to cholinergic contraction in SCI bladders. A similar shift from M3 to M2 receptor mediated contraction has been described in patients with neurogenic bladder [19].…”

The validation of a functional, isolated pig bladder model for physiological experimentation

“…The contractile properties of the bladder are controlled by descending central inhibition and activation which overlay a complex autonomous (spontaneous) activity. The latter is most readily characterized when the bladder is freed from central control (Van Duyl, 1985; Coolsaet et al, 1993; Sugaya and de Groat, 2000; Drake et al, 2003a,b; Gevaert et al, 2009). It is manifest as localized contractions and stretches of the bladder wall which can be enhanced by increases in intravesical volume or by applying a muscarinic receptor agonist at low concentrations (Gillespie et al, 2003; Lagou et al, 2004).…”

Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

“…In this study, a low dose (25 μM) of Oxo-M increased NVCs in SCI rats. The increased expression of M2 mAChR subtype could be involved in the increased sensitivity for Oxo-M. Gevaert et al 28 reported a significant increase of M2 subtype mRNA in the whole bladder at 3 weeks post-SCI rats and a significant decrease of M3 subtype mRNA at 24 hours post-SCI. An increased density of M2 protein and a decrease of M3 protein have been reported in decentralised 14 , obstructed 15 , and neurogenic 17 rat bladders.…”