P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin.
OBJECTIVE
The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex. The aim of this study was to investigate the possible role of P2X3-positive innervation in this pathological voiding reflex by comparing suburothelial P2X3 immunoreactivity of controls and in patients with NDO before and after intravesical RTX.


METHODS
Bladder biopsies were obtained from 8 controls and 20 patients with refractory NDO enrolled in a trial of intravesical RTX. P2X3 nerve fibre density and intensity were studied in the specimens by immunohistochemistry.


RESULTS
P2X3-IR nerve fibres were significantly increased in patients with NDO compared to controls (p=0.014). Thirteen patients had pre- and post-RTX biopsies available for immunohistochemistry; 5 of them responded clinically and 8 were non-responders. In the 5 patients who responded to RTX, there was a significant decrease in P2X3-positive fibres (p=0.032), whereas in non-responders, P2X3-IR nerve fibre density did not change significantly.


CONCLUSIONS
In patients with NDO, the numbers of P2X3-IR nerve fibres were increased in the suburothelium. There was a significant decrease in P2X3 immunoreactivity in responders to RTX, indicating a potential pathophysiological role for the P2X3 expressing fibres.
Brady
Ciaran M
CM
Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
Apostolidis
Apostolos
A
Yiangou
Yiangos
Y
Baecker
Preston A
PA
Ford
Anthony P
AP
Freeman
Alex
A
Jacques
Thomas S
TS
Fowler
Clare J
CJ
Anand
Praveen
P
D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation* / Q000473:pathology; D009498:Neurotoxins; D018048:Receptors, Purinergic P2 / Q000032:analysis*; D058477:Receptors, Purinergic P2X3; D001750:Urinary Bladder, Neurogenic / Q000473:pathology*
D004224:Diterpenes; D009498:Neurotoxins; C546407:P2RX3 protein, human; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C024353:resiniferatoxin