Lumbosacral sensory neuronal activity is enhanced by activation of urothelial purinergic receptors

Abstract Urothelial purinergic receptors are important for the regulation of afferent sensory pathways in bladder pain and overactivity. Using in vivo electrophysiological recordings we evaluated the activity of spinal dorsal horn neurons in female rats at the L6/S1 level when urinary bladder pressure was abruptly increased. Intravesical infusion of ATP and systemic application of suramin allowed us to evaluate the contribution of urothelial purinergic receptors. Rats were anesthetized with isofluorane. Suprapubic, venous and tracheal catheters were implanted. Laminectomy was performed at the L6–S1 spinal levels. The cervical spinal cord was transected, and rats were mechanically pithed. Anesthesia was stopped, rats were ventilated, and a muscle relaxant was administered. The frequency of spinal neural activity was recorded via tungsten electrodes inserted into the dorsal horn at the L6–S1 level. The signal was amplified, filtered and recorded with a data acquisition system at 10 kHz sampling rate. Vital signs as well as bladder pressure were monitored in real time. We evaluated field potentials during intravesical pressure steps ranging from 0 to 60 cm H2O in (A) control (saline in the bladder), (B) after stimulation of urothelial purinergic receptors (1 mM vesical ATP), and (C) after the intravenous application of the non-specific purinergic antagonist suramin (100 mg/kg). Pressure steps were maintained for 1 min followed by 3 min for recovery. Only neurons that showed an increased activity during bladder distention were evaluated. Under control conditions, the generation of field potentials increased concomitantly with bladder pressure steps, showing an activity change threshold between 20 and 40 cm H2O. Intravesical application of 1 mM ATP produced an increase in baseline activity, indicative of noxious stimulation, and spinal neuronal activity markedly increased above 40 cm H2O pressure. Systemic suramin prevented the increase in neural activity in response to pressure changes, even after intravesical ATP. These results suggest that urothelial purinergic receptors are important modulators of lumbosacral dorsal spinal neuronal activity. The inhibitory effects of suramin imply that enhanced lumbosacral neuronal signals result from activation of C-fibers during noxious bladder stimulation.

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