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The Journal of Neuroscience, October 11, 2006, 26(41):10499-10507; doi:10.1523/JNEUROSCI.1997-06.2006

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Cellular/Molecular
Deletion of Annexin 2 Light Chain p11 in Nociceptors Causes Deficits in Somatosensory Coding and Pain Behavior

Thomas Foulkes,¹ Mohammed A. Nassar,¹ Tim Lane,¹ Elizabeth A. Matthews,² Mark D. Baker,¹ Volker Gerke,³ Kenji Okuse,⁴ Anthony H. Dickenson,² and John N. Wood¹

¹Molecular Nociception Group, Department of Biology, and ²Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom, ³Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, 48149 Muenster, Germany, and ⁴Division of Cell and Molecular Biology, Imperial College, London SW7 2AZ, United Kingdom

Correspondence should be addressed to John N. Wood, Molecular Nociception Group, Department of Biology, University College London, Gower Street, London WC1E 6BT, UK. Email: j.wood{at}ucl.ac.uk

The S100 family protein p11 (S100A10, annexin 2 light chain) is involved in the trafficking of the voltage-gated sodium channel Na_V1.8, TWIK-related acid-sensitive K⁺ channel (TASK-1), the ligand-gated ion channels acid-sensing ion channel 1a (ASIC1a) and transient receptor potential vanilloid 5/6 (TRPV5/V6), as well as 5-hydroxytryptamine receptor 1B (5-HT_1B), a G-protein-coupled receptor. To evaluate the role of p11 in peripheral pain pathways, we generated a loxP-flanked (floxed) p11 mouse and used the Cre-loxP recombinase system to delete p11 exclusively from nociceptive primary sensory neurons in mice. p11-null neurons showed deficits in the expression of Na_V1.8, but not of annexin 2. Damage-sensing primary neurons from these animals show a reduced tetrodotoxin-resistant sodium current density, consistent with a loss of membrane-associated Na_V1.8. Noxious coding in wide-dynamic-range neurons in the dorsal horn was markedly compromised. Acute pain behavior was attenuated in certain models, but no deficits in inflammatory pain were observed. A significant deficit in neuropathic pain behavior was also apparent in the conditional-null mice. These results confirm an important role for p11 in nociceptor function.

Key words: conditional knock-out; Cre-loxP; Na_V1.8; neuropathic pain; p11; pain behavior

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Received May 10, 2006; revised Aug. 18, 2006; accepted Aug. 21, 2006.

Correspondence should be addressed to John N. Wood, Molecular Nociception Group, Department of Biology, University College London, Gower Street, London WC1E 6BT, UK. Email: j.wood{at}ucl.ac.uk

This article has been cited by other articles:

				Z.-N. Zhang, Q. Li, C. Liu, H.-B. Wang, Q. Wang, and L. Bao The voltage-gated Na+ channel Nav1.8 contains an ER-retention/retrieval signal antagonized by the {beta}3 subunit J. Cell Sci., October 1, 2008; 121(19): 3243 - 3252. [Abstract] [Full Text] [PDF]

				J. A. R. Ostman, M. A. Nassar, J. N. Wood, and M. D. Baker GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9 J. Physiol., February 15, 2008; 586(4): 1077 - 1087. [Abstract] [Full Text] [PDF]

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