Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment

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Abstract
Effects of purinergic agonists (α,β-meATP and ATP) and cyclophosphamide-induced cystitis on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced spontaneous bladder contractions that were accompanied by multiunit afferent firing. Intravesical administration of 40 and 130 μM α,β-meATP increased afferent firing from 27 ± 3 to 53 ± 6 and 61 ± 2 spikes/s, respectively, but did not change the maximum amplitude of spontaneous bladder contractions. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. α,β-meATP decreased the voltage threshold from 9.0 ± 1.2 to 3.5 ± 0.5 V (0.15-ms pulse duration) and increased the area of the APs (82% at 80-V stimulus intensity). These effects were blocked by TNP-ATP (30 μM). ATP (2 mM) applied in the bath produced similar changes in BAN activity. These effects were blocked by bath application of PPADS (30 μM). Neither TNP-ATP nor PPADS affected BAN activity induced by distension of the bladder. Cystitis induced by pretreatment of the rats with cyclophosphamide (100 mg/kg ip) increased afferent firing in response to isotonic bladder distension (10–40 cmH2O), decreased the threshold, and increased the area of evoked APs. The increase in afferent firing at 10 cmH2O intravesical pressure was reduced 52% by PPADS. These results indicate that purinergic agonists acting on P2X receptors and cystitis induced by cyclophosphamide can increase excitability of the BANs.