Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 1 August 2008:
Vol. 321. no. 5889, pp. 702 - 705
DOI: 10.1126/science.1156916
Prev | Table of Contents | Next

Reports

The Cell and Molecular Basis of Mechanical, Cold, and Inflammatory Pain

Bjarke Abrahamsen,1 Jing Zhao,1 Curtis O. Asante,2 Cruz Miguel Cendan,1 Steve Marsh,2 Juan Pedro Martinez-Barbera,3 Mohammed A. Nassar,1 Anthony H. Dickenson,2 John N. Wood1*

Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Nav1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.

1 Molecular Nociception Group, University College London (UCL), Gower Street, London, WC1E 6BT, UK.
2 Department of Pharmacology, UCL, Gower Street, London, WC1E 6BT, UK.
3 Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.

* To whom correspondence should be addressed. E-mail: j.wood{at}ucl.ac.uk

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Sensory Axon-Derived Neuregulin-1 Is Required for Axoglial Signaling and Normal Sensory Function But Not for Long-Term Axon Maintenance.
F. R. Fricker, N. Zhu, C. Tsantoulas, B. Abrahamsen, M. A. Nassar, M. Thakur, A. N. Garratt, C. Birchmeier, S. B. McMahon, J. N. Wood, et al. (2009)
J. Neurosci. 29, 7667-7678
   Abstract »    Full Text »    PDF »
Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli.
D. J. Cavanaugh, H. Lee, L. Lo, S. D. Shields, M. J. Zylka, A. I. Basbaum, and D. J. Anderson (2009)
PNAS 106, 9075-9080
   Abstract »    Full Text »    PDF »
Structural Determinants of Drugs Acting on the Nav1.8 Channel.
L. E. Browne, F. E. Blaney, S. P. Yusaf, J. J. Clare, and D. Wray (2009)
J. Biol. Chem. 284, 10523-10536
   Abstract »    Full Text »    PDF »
TRPA1 acts as a cold sensor in vitro and in vivo.
Y. Karashima, K. Talavera, W. Everaerts, A. Janssens, K. Y. Kwan, R. Vennekens, B. Nilius, and T. Voets (2009)
PNAS 106, 1273-1278
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)