A Non-Anesthetized Mouse Model for Recording Sensory Urinary Bladder Activity

Kristopher Roach,Lawrence M Dagrosa,Michal Ursiny,Thomas J Heppner,Peter Zvara,Andrew J Wright,Mark T Nelson,Bennett Shapiro

doi:10.3389/fneur.2010.00127

Abstract

The goal of this study was to develop an in vivo awake mouse model for extracellular bladder sensory nerve recording. A bipolar 125-μm silver electrode was positioned under a single postganglionic bladder nerve. Efferent nerve signals were eliminated by tying off the postganglionic bladder nerve between the major pelvic ganglion and the recording electrode. Sensory nerve activity was measured in the conscious animals 48 h after surgery during continuous intravesical infusion of 0.9% saline/0.5% acetic acid followed by 0.5% acetic acid with capsazepine (10 μM) at a rate of 0.75 ml/h. Continuous infusion of 0.9% NaCl led to a gradual increase in the frequency of sensory nerve firing that peaked upon reaching threshold pressure. Non-micturition contractions were observed in some animals during filling and other animals exhibited only minimal pressure fluctuations; both types of events were associated with a rise in sensory nerve activity. Intravesical infusion of 0.5% acetic acid reduced the intermicturition interval. This was associated with a 2.1-fold increase in bladder pressure during filling and a two-fold increase at both threshold and micturition pressures. Concurrent with these changes, sensory activity increased 2.8-fold during filling and 2.4-fold at threshold pressure. Subsequent intravesical infusion of capsazepine in 0.5% acetic acid reduced filling and threshold pressures by 21 and 31.2%, respectively, and produced corresponding decreases of 36 and 23.4% in sensory nerve activity. The current study shows that multifiber sensory nerve recordings can be reproducibly obtained from conscious mice.

Highlights

The afferent limb of the micturition reflex presents an attractive target for pharmacological intervention in the treatment of bladder dysfunction, but the animal models currently available for testing potential therapeutic agents have limitations (Andersson, 2002)
Intravesical infusion of 0.5% acetic acid evoked a significant reduction in intermicturition intervals coupled with an increase in average filling and threshold pressures
Multifiber bladder sensory nerve activity during bladder filling Continuous filling with saline in vivo generated a reproducible pattern of afferent nerve discharge (n = 8)

Summary

Introduction

The afferent limb of the micturition reflex presents an attractive target for pharmacological intervention in the treatment of bladder dysfunction, but the animal models currently available for testing potential therapeutic agents have limitations (Andersson, 2002). Animal models used to date require the use of anesthesia, which exerts its effects by enhancing inhibitory and/or suppressing excitatory neural output, likely compromising nerve activity recordings (Habler et al, 1990; Hara and Harris, 2002; Malley and Vizzard, 2002) To address these limitations, we developed a new method for recording sensory nerve activity in vivo in the conscious animal. Bladder-specific afferent neural discharge and corresponding changes in intravesical pressure during bladder filling were recorded The validity of this model was tested by recording extracellular bladder sensory nerve activity in healthy animals and after inducing bladder overactivity with 0.5% acetic acid. The functional contribution of C-fibers to the bladder sensory discharge during noxious/chemically induced bladder irritation was assessed using the TRPV1 receptor antagonist, capsazepine (Daly et al, 2007)

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