Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice

• Published in: Nature (London) 2000-10, Vol.407 (6807), p.1011-1015
• Main Authors: Cockayne, Debra A., Hamilton, Sara G., Zhu, Quan-Ming, Dunn, Philip M., Zhong, Yu, Novakovic, Sanja, Malmberg, Annika B., Cain, Gary, Berson, Amy, Kassotakis, Laura, Hedley, Linda, Lachnit, Wilhelm G., Burnstock, Geoffrey, McMahon, Stephen B., Ford, Anthony P. D. W.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - physiology; Animals; ATP; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Targeting; Humanities and Social Sciences; letter; Mice; multidisciplinary; Neurons; Neurons - physiology; Neurons, Afferent - physiology; Nociceptors - physiology; Pain; Receptors, Purinergic P2 - physiology; Receptors, Purinergic P2X3; Reflex, Abnormal; Reflexes; Rodents; Science; Science (multidisciplinary); Urinary bladder; Urinary Bladder - innervation; Urinary Bladder - physiology; Urine; Urodynamics; Vertebrates: urinary system
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35039519

Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs 1 . The ATP receptor P2X 3 is selectively expressed on small diameter sensory neurons 2 , 3 , 4 , supporting this hypothesis. Here we show that mice deficient in P2X 3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X 3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X 3 -null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X 3 -null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X 3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X 3 does not alter sensory neuron innervation density. Thus, P2X 3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X 3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder.