luda [dot] diatchenko [at] mcgill [dot] ca (Email)
Persistent pain is a part of many common human clinical conditions, yet the current ability to diagnose and manage these conditions is inadequate. Pain perception is one of the most complicated measurable traits, as it is composed of an aggregate of several other measurable phenotypes associated with peripheral and central nervous system dynamics, stress responsiveness, and inflammatory state. It is generally accepted that complex traits, like pain perception, result from the interplay between environmental exposures and multiple genetic variants. However, little is known about the nature of these genetic variants. Because of the established roles of environmental exposures and the commonly held view that pain perception is an unquantifiable “subjective” experience, a genetic basis for pain perception has long been questioned. Recent and rapidly developing discoveries in the field of pain genetics have provided evidence for a substantial role for genetic background on pain perception and clinical pain phenotypes. These findings provide unique opportunities to identify new genetic variants that contribute to pain phenotypes.
The Diatchenko lab investigates the psychological, molecular, cellular, and genetic pathways that mediate both acute and persistent pain states. Their primary goal is to identify the critical elements of human genetic variability contributing to pain sensitivity and pathophysiological pain states that will enable individualized treatments and therapies. Other related research endeavors include molecular hierarchy of functional SNPs (single-nucleotide polymorphisms) and SNP-depend regulation of gene expression, underlying molecular pain signaling. Answering these questions requires collaboration with experts in both clinical and basic biological sciences. Such collaborative activities allow the Diatchenko group to take basic genetic findings all the way from human association studies, through molecular and cellular mechanisms, to animal models, and ultimately to human clinical trials.
Luda Diatchenko, MD, PhD is a Canada Excellence Research Chair in Human Pain Genetics, Professor, Faculty of Medicine, Department of Anesthesia, and Faculty of Dentistry, at McGill University, Alan Edwards Centre for Research on Pain. She earned her MD and PhD in the field of Molecular Biology from the Russian State Medical University (formerly RGMU). Dr. Diatchenko started her career in industry, she was a Leader of the RNA Expression Group at Clontech, Inc., and subsequently, Director of Gene Discovery at Attagene, Inc. During this time, Dr. Diatchenko was actively involved in the development of several widely-used and widely-cited molecular tools for the analysis of gene expression and regulation. Dr. Diatchenko’s academic career started at 2000 in the Center for Neurosensory Disorders at the University of North Carolina. Her research since then is focused on determining the cellular and molecular biological mechanisms by which functional genetic variations impact human pain perception and risk of development of chronic pain conditions, enabling new approaches to identify new drug targets, treatment responses to analgesics, and diagnostic. Dr. Diatchenko is a frequent speaker at national and international pain research conferences. Multiple collaborative activities allow the Diatchenko group to take basic genetic findings all the way from human association studies, through molecular and cellular mechanisms, to animal models, and ultimately to human clinical trials. In total, Dr. Diatchenko have authored or co-authored over 100 peer-reviewed research papers (plus 10 book chapters) in journals with 2011 Thomson ISI Impact Factors up to 34.8, from which 34 (44%) of refereed articles in journals having an Impact Factor >5.0. She is a member and an active officer of several national and international scientific societies, including the International Association for the Study of Pain, the American Pain Society, and the American Society of Human Genetics.
Slade GD, Smith S, Zaykin D, Tchivileva I, Gibson DG, Yuryev A, Mazo I, Bair E, Fillingim R, Ohrbach R, Maixner W, Diatchenko L. Facial pain with localized and widespread manifestations: separate pathways of vulnerability. Pain. 2013 Nov;154(11):2335-43.
Diatchenko L, Fillingim RB, Smith SB, Maixner W. The Phenotypic and Genetic Signatures of Common Musculoskeletal Pain Conditions. Nature Rev Rheumatology. 2013 Jun;9(6):340-50.
Belfer I, Segall SK, Lariviere, WR, Smith SB, Dai F, Slade GG, Rashid NU, Mogil JS, Campbell CM, Edwards, RR, Liu Q, Bair E, Maixner W, Diatchenko L. Pain modality- and sex-specific effects of COMT genetic functional variants. Pain. 2013 Aug;154(8):1368-76.
Neely GG, Rao S, Costigan M, Mair N, Racz I, Milinkeviciute G, Meixner A, Nayanala S, Griffin RS, Belfer I, Dai F, Smith S, Diatchenko L, Marengo S, Haubner BJ, Novatchkova M, Gibson DG, Maixner W, Pospisilik JA, Hirsch E, Whishaw IQ, Zimmer A, Gupta V, Sasaki J, Kanaho Y, Sasaki T, Kress M, Woolf CJ, Penninger JM. Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. PLoS Genet. 2012 Dec;8(12):e1003071. Epub 2012 Dec 6.
Chen H, Slade G, Lim PF, Miller V, Maixner W, Diatchenko L. Relationship between temporomandibular disorders, widespread palpation tenderness, and multiple pain conditions: a case-control study. J Pain. 2012 Oct;13(10):1016-27.
6Tsao D, Wieskopf JS, Rashid N, Sorge RE, Redler RL, Segall SK, Mogil JS, Maixner W, Dokholyan NV, Diatchenko L. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity. Mo Pain 2012;8(1):25.
Sorge RE, Trang T, Dorfman R, Smith SB, Beggs S, Ritchie J, Austin J-S, Zaykin DV, Meulen HV, Costigan M, Herbert TA, Yarkoni-Abitbul M, Tichauer D, Livneh J, Gershon E, Zheng M, Tan K, John SL, Slade GD, Jordan J, Woolf CJ, Peltz G, Maixner W, Diatchenko L, Seltzer Z, Salter MW, Mogil JS. Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat Med 2012;18(4):595-9.
Maixner W, Diatchenko L, Dubner R, Fillingim RB, Greenspan JD, Knott C, Ohrbach R, Weir B, Slade GD. Orofacial Pain Prospective Evaluation and Risk Assessment Study – The OPPERA Study. J of Pain 2011:12(11; Supplement):T4-T11.e2. PMCID:
Smith SB, Maixner DW, Greenspan JD, Dubner R, Fillingim RB, Ohrbach R, Knott C, Slade GD, Bair E, Gibson DG, Zaykin DV, Weir BS, Maixner W, Diatchenko L. Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study. J of Pain 2011;12(11; Supplement):T92-T101.
Serohijos AWR, Yin S, Ding F, Gauthier J, Gibson DG, Maixner W, Dokholyan NV, Diatchenko L. Structural basis for mu-opioid receptor binding and activation. Structure 2011;19(11):1683-90. PMCID: PMC3217204
Smith S, Maixner D, Fillingim R, Slade G, Gracely R, Ambrose K, Zaykin D, Hyde C, John S, Tan K, Maixner W, Diatchenko L. Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia. Arthritis Rheum 2011 Sep 8. [Epub ahead of print] PMCID: PMC3237946
Tsao D, Shabalina SA, Gauthier J, Dokholyan NV, Diatchenko L. Disruptive mRNA folding increases translational efficiency of catechol-O-Methyltransferase variant. Nucleic Acids Res 2011;39(14):6201-12. Epub 2011 Apr 12. PMCID: PMC3152328
Neely G, Hess A, Costigan M, Keene A, Goulas S, Langeslag M, Griffin R, Belfer I, Feng Dai, Smith S, Diatchenko L, Gupta V, Xia C, Amann S, Kreitz S, Heindl-Erdmann C, Ly C, Arora C, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Gibson DG, Truong D, Schramek D, Zoranovic T, Cronin S, Angjeli B, Brune K, Dietzl G, Maixner W, Meixner A, Thomas W, Pospisilik A, Alenius M, Kress M, Subramaniam S, Garrity P, Bellen H, Woolf C, Penninger JM. A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionary conserved pain gene. Cell 2010;143(4):628-38. PMCID: PMC3040441
Shabalina SA, Zaykin DV, Gris P, Ogurtsov AY, Gauthier J, Shibata K, Tchivileva IE, Belfer I, Mishra B, Kiselycznyk C, Wallace MR, Staud R, Spiridonov NA, Max MB, Goldman D, Fillingim RB, Maixner W, Diatchenko L. Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet 2009;18(6):1037-51. Epub 2008 Dec 22. PMCID: PMC2649019
Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain 2007;128:199-208. Epub 2006 Nov 7.
Diatchenko L, Nackley AG, Tchivileva I, Shabalina SA, Maixner W. Genetic Architecture of Human Pain Perception: Clinical Implications. Trends Genet 2007;23(12):605-13. Epub 2007 Nov. 26. Review.
Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, Maixner W, Diatchenko L. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006 Dec 22;314(5807):1930-3.