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Science 321 (5889): 702-705

Copyright © 2008 by the American Association for the Advancement of Science

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*

Abstract: 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


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