It has been proposed that chronic ischemia in the urinary bladder causes overactive bladder (OAB) related changing of neural, urothelium and smooth muscle structures, and leads to inflammation and relax and/or contractile dysfunctions [1]. Such chronic bladder ischemia (CBI) may also lead to the bladder sensory dysfunction. However, there has been no study directly investigating the sensory afferent transductions in pathophysiological conditions of CBI. This study aimed to evaluate the characteristics of mechanosensitive single-unit afferent activities (SAAs) innervating the bladder in male rat model of CBI.

Male Sprague–Dawley rats (16 weeks old) were divided into the sham and CBI groups (N=11 in each group). The CBI group underwent balloon-induced endothelial injury of the iliac arteries and was fed a 2% cholesterol diet for 8 weeks, whereas the sham group underwent only bilateral inguinal incisions without balloon-induced endothelial injury and was fed a regular diet for 8 weeks [2].
In the SAAs measurements, rats were anesthetized with urethane (1.2 g/kg, intraperitoneally). After the laminectomy, fine filaments were dissected from the left L6 dorsal roots and placed across a bipolar electrode for monitoring SAAs. Nerve fibers primarily originating from the bladder were identified by electrical stimulation of the left pelvic nerve and by bladder distension. Nerves with conduction velocities (CV) more than 2.5 m/s were designated as Aδ-fibers and those with CV less than 2.5 m/s as C-fibers [3]. The intravesical pressure and SAAs were recorded and analyzed during constant filling with saline until the intravesical pressure reached 30 cmH2O. In addition, bladder compliance was simply calculated between the start and end of the saline-instillation into the bladder during SAAs measurements.

Totally 90 single afferent fibers were isolated (Sham group: Aδ-fibers: n=22, CV: 5.35 ± 0.89 m/s, C-fibers: n=25, CV: 1.79 ± 0.05 m/s, CBI group: Aδ-fibers: n=23, CV: 4.33 ± 0.43 m/s, C-fibers: n=20, CV: 1.89 ± 0.08 m/s). The CBI group showed significantly higher SAAs of C-fibers than those of the Sham group. In contrast, SAAs of Aδ-fibers did not significantly differ between the groups, although the values tended to decrease in CBI group (Figure 1). No significant differences of bladder compliance (mL/Δ cm H2O) were found between the groups (Figure 2).

Present CBI model, in which endothelial injury and hyperlipidemia induced arteriosclerosis in the common iliac artery, has been exhibited an increase in voiding frequency and a decrease in mean voided volume, suggesting pathophysiological condition of OAB [2]. Present study demonstrated that SAAs of C-fibers, not of Aδ-fibers, facilitated in CBI rats. It has been hypothesized that Aδ-fibers responding to normal bladder sensation, whereas C-fibers responding to abnormal (i.e., noxious and inflammatory) stimuli as “silent” fibers. CBI-induced hyperactivity of C-fibers in the present study may support such hypothesize. On the other hand, SAAs of Aδ-fibers rather tended to decrease in the CBI group. This finding may indicates that myelinated Aδ-fibers were more vulnerable to ischemia.
Bladder compliance did not differ between the groups. This parameter has been influenced by various factors including intrinsic properties of the bladder wall and neuromuscular factors through the signal of sympathetic reflexes. At least in the present study, bladder tonus during bladder distension may have been negligibly influenced by CBI.

The present study indicated that CBI facilitated C-fiber afferent activity, suggesting heightened bladder sensation and urgency in OAB. This is the first direct demonstration of a relationship between the mechanosensitive afferent fiber activities and arteriosclerosis related CBI under pathophysiological conditions.

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