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© Uwe Maskos
Tranche d'hippocampe de souris colorée avec deux toxines spécifiques de sous-types de récepteur nicotinique, en rouge (grains), et en vert (corps cellulaires). L'hippocampe est la zone du cerveau qui gère la mémoire spatiale.
Publication : Science translational medicine

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Science translational medicine - 13 May 2015

Wieskopf JS, Mathur J, Limapichat W, Post MR, Al-Qazzaz M, Sorge RE, Martin LJ, Zaykin DV, Smith SB, Freitas K, Austin JS, Dai F, Zhang J, Marcovitz J, Tuttle AH, Slepian PM, Clarke S, Drenan RM, Janes J, Al Sharari S, Segall SK, Aasvang EK, Lai W, Bittner R, Richards CI, Slade GD, Kehlet H, Walker J, Maskos U, Changeux JP, Devor M, Maixner W, Diatchenko L, Belfer I, Dougherty DA, Su AI, Lummis SC, Imad Damaj M, Lester HA, Patapoutian A, Mogil JS

Link to Pubmed [PMID] – 25972004

Sci Transl Med 2015 May;7(287):287ra72

Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6’s role in analgesia is at least partially due to direct interaction and cross-inhibition of α6* nAChRs with P2X2/3 receptors in DRG nociceptors. Finally, we establish the relevance of our results to humans by the observation of genetic association in patients suffering from chronic postsurgical and temporomandibular pain.

http://www.ncbi.nlm.nih.gov/pubmed/25972004