Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3 receptors

It is well known that urinary bladder sensation requires the activation by ATP of ionotropic purinergic P2X3/P2X2/3 receptors located in bladder afferent C-fibres. Furthermore, in rat models of neurogenic bladder hyperactivity the release of ATP from the bladder urothelium is greater than ATP release in neurally intact rats. Therefore, the activation of purinergic receptors in bladder sensory fibres seems to be a sentinel event for the development of bladder hyperactivity after spinal cord injury. We found that inhibition of P2X3/P2X2/3 purinergic receptors decreased the frequency of sensory field potentials evoked by activation of bladder noxious pathways. At the same time, the pharmacological blockade of these receptors significantly decreased the frequency of non-voiding contractions in rats with neurogenic bladder hyperactivity. The present study uncovers sensory purinergic receptors as potential therapeutic targets to treat neurogenic bladder hyperactivity, especially when the release of ATP from the urothelium is elevated.