Sensory nerves in the periphery respond to noxious stimuli that produce pain, thermal stimuli sensed as heat or cold, and mechanical stimuli perceived as touch. Two groups (Cockayne et al. and Souslova et al.) studied how sensory perception was altered in mice when the gene for the P2X3 adenosine triphosphate (ATP) receptor was knocked out. A third group (Price et al.) focused on sensory deficits in mice lacking the gene for the sodium channel BNC1, which is not a voltage-gated channel. The BNC1-/- mice exhibited decreased responsiveness to mechanical stimuli sensed by the class of rapidly adapting mechanoreceptors. The BNC1 channel is normally expressed by nerves found at the base of hair follicles consistent with its having an essential role in touch perception. The P2X3 knockout mice demonstrated decreased pain-related behavior. Furthermore, the P2X3-/- mice lost a rapidly desensitizing ATP-induced current in dorsal root ganglia and had altered ATP-induced currents in nodose ganglia consistent with a role for the P2X3 receptor in nociception. Additional phenotypes were also noted in the P2X3-/- mice. Cockayne et al. reported that the mice urinated less frequently and provided evidence for the P2X3 receptor in bladder volume reflexes; Souslova et al. reported a defect in neuronal responsiveness to nonnoxious thermal stimuli (temperatures below 45°C but greater than 37°C). Although these results suggest that the P2X3 receptor may be a candidate for pharmacological intervention in treating urinary incontinence and pain management, Souslova et al. found that the mice were hyperalgesic under conditions of chronic inflammation. The accompanying commentary by Cook and McCleskey highlights these caveats.
Cockayne, D.A., Hamilton, S.G., Zhu, Q.-M., Dunn, P.M., Zhong, Y., Novakovic, S., Malmberg, A.B., Cain, G., Berson, A., Kassotakis, L., Hedley, L., Lachnit, W.G., Burnstock, G., McMahon, S.B., and Ford, A.P.D.W. (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407: 1011-1015. [Online Journal]
Souslova, V., Cesare, P., Ding, Y., Akopian, A.N., Stanfa, L., Suzuki, R., Carpenter, K., Dickenson, A., Boyce, S., Hill, R., Nebenius-Oosthuizen, D., Smith, A.J.H., Kidd, E.J., and Wood, J.N. (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407: 1015-1017. [Online Journal]
Price, M.P., Lewin, G.R., McIlwrath, S.L., Cheng, C., Xie, J., Heppenstall, P.A., Stucky, C.L., Mannsfeldt, A.G., Brennan, T.J., Drummond, H.A., Qiao, J., Benson, C.J., Tarr, D.E., Hrstka, R.F., Yang, B., Williamson, R.A., and Welsh, M.J. (2000) The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 407: 1007-1011. [Online Journal]
Cook, S.P., and McCleskey, E.W. (2000) ATP, pain and a full bladder. Nature 407: 951-952. [Online Journal]