Dr. Luda Diatchenko
Professor - Departments of AnesthesiaProfessor - Faculty of Dentistry
Associate Member - Medicine, Division of Experimental Medicine
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.
1. Functional molecular genetic analysis of the Association Studies results of human chronic pain conditions.
2. Assessment of enzymatic activity of COMT homologs.
3. Study on genotype dependent variation within COMT gene locus in post-surgical opioid-induced analgesia.
- 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.