The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

Author:

Wieskopf Jeffrey S.1,Mathur Jayanti2,Limapichat Walrati3,Post Michael R.3,Al-Qazzaz Mona4,Sorge Robert E.1,Martin Loren J.1,Zaykin Dmitri V.5,Smith Shad B.6,Freitas Kelen7,Austin Jean-Sebastien1,Dai Feng8,Zhang Jie2,Marcovitz Jaclyn1,Tuttle Alexander H.1,Slepian Peter M.1,Clarke Sarah1,Drenan Ryan M.9,Janes Jeff2,Al Sharari Shakir10,Segall Samantha K.6,Aasvang Eske K.11,Lai Weike8,Bittner Reinhard12,Richards Christopher I.13,Slade Gary D.14,Kehlet Henrik11,Walker John2,Maskos Uwe15,Changeux Jean-Pierre15,Devor Marshall16,Maixner William6,Diatchenko Luda617,Belfer Inna8,Dougherty Dennis A.3,Su Andrew I.18,Lummis Sarah C. R.4,Imad Damaj M.7,Lester Henry A.19,Patapoutian Ardem20,Mogil Jeffrey S.1

Affiliation:

1. Department of Psychology and Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec H3A 1B1, Canada.

2. Genomic Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

3. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

4. Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.

5. National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.

6. Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

7. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23219, USA.

8. Departments of Anesthesiology and Human Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA.

9. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.

10. Department of Pharmacology, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.

11. Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen University, 2100 Copenhagen, Denmark.

12. Department of Surgery, Marienhospital Stuttgart, 70199 Stuttgart, Germany.

13. Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.

14. Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

15. Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS UMR 3571, Département de Neuroscience, Institute Pasteur, 75724 Paris, France.

16. Department of Cell and Developmental Biology, Institute of Life Sciences and Center for Research on Pain, Hebrew University of Jerusalem, Jerusalem 91904, Israel.

17. Faculty of Dentistry, Department of Anesthesia, and Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec H3A 1G1, Canada.

18. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

19. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

20. Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, and Howard Hughes Medical Institute, La Jolla, CA 92037, USA.

Abstract

Finding that nicotinic receptors containing the α6 subunit, but not the α4, inhibit chronic pain points to a new set of potential therapeutic drugs.

Funder

NIH

Canadian Institutes for Health Research

Louise and Alan Edwards Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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