Human Molecular Genetics Advance Access published online on November 10, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddi013
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 University of North Carolina at Chapel Hill, Comprehensive Center for Inflammatory Disorders, Columbia St., CB#7455, 2190 Old Dental Bld., Chapel Hill, NC, 27599, USA; Attagene, Inc., 7030 Kit Creek Road, Research Triangle Park NC, 27560, USA
* To whom correspondence should be addressed. Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS), and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population and five combinations of these haplotypes are strongly associated (P=0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity compared to the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD.
Article
Genetic basis for individual variations in pain perception and the development of a chronic pain condition
2 University of Adelaide, Australian Research Centre for Population Oral Health, Frome Rd, SA 5005, Adelaide, Australia
3 University of North Carolina, Comprehensive Center for Inflammatory Disorders, Columbia St., CB#7455, Chapel Hill, NC, 27599
4 Chulalongkorn University, Department of Oral Medicine, 254 Phyathai Road, Bangkok, 10330 Thailand
5 NIDCR, NIH, Pain & Neurosensory Mechanisms Branch, Bldg 10, Rm 3C-405, Bethesda, MD 20892-1258, USA; Laboratory of Neurogenetics, NIAAA, NIH, 12420 Parklawn Drive, Park 5 Building, Rockville, MD, 20852, USA
6 Laboratory of Neurogenetics, NIAAA, NIH, 12420 Parklawn Drive, Park 5 Building, Rockville, MD, 20852, USA
7 NCBI, NIH, 6404 Landon Lane, 8600 Rockville Pike, Bethesda, MD 20894, USA
8 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Ul. Miklukho-Maklaya, 16/10, 117997, Moscow, Russia
9 NIDCR, NIH, Pain & Neurosensory Mechanisms Branch, Bldg 10, Rm 3C-405, Bethesda, MD 20892-1258, USA
10 Attagene, Inc., 7030 Kit Creek Road, Research Triangle Park NC, 27560, USA
Luda Diatchenko, E-mail: lbdiatch{at}email.unc.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. A. Adegbola Can Heterogeneity of Chronic Sickle-Cell Disease Pain Be Explained by Genomics? A Literature Review Biol Res Nurs, July 1, 2009; 11(1): 81 - 97. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Clinch and C. Eccleston Chronic musculoskeletal pain in children: assessment and management Rheumatology, May 1, 2009; 48(5): 466 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Shabalina, D. V. Zaykin, P. Gris, A. Y. Ogurtsov, J. Gauthier, K. Shibata, I. E. Tchivileva, I. Belfer, B. Mishra, C. Kiselycznyk, et al. Expansion of the human {micro}-opioid receptor gene architecture: novel functional variants Hum. Mol. Genet., March 15, 2009; 18(6): 1037 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Scrivani, D. A. Keith, and L. B. Kaban Temporomandibular Disorders N. Engl. J. Med., December 18, 2008; 359(25): 2693 - 2705. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sonnesen and P. Svensson Temporomandibular disorders and psychological status in adult patients with a deep bite Eur J Orthod, December 1, 2008; 30(6): 621 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ruiz, E. Davis, and E. P. Martins Courtship attention in sagebrush lizards varies with male identity and female reproductive state Behav. Ecol., November 1, 2008; 19(6): 1326 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Macrae Chronic post-surgical pain: 10 years on Br. J. Anaesth., July 1, 2008; 101(1): 77 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Skorpen, E. Laugsand, P Klepstad, and S Kaasa Variable response to opioid treatment: any genetic predictors within sight? Palliative Medicine, June 1, 2008; 22(4): 310 - 327. [Abstract] [PDF]
|
|
|
|
 |
|
 S. G. Khasar, J. Burkham, O. A. Dina, A. S. Brown, O. Bogen, N. Alessandri-Haber, P. G. Green, D. B. Reichling, and J. D. Levine Stress Induces a Switch of Intracellular Signaling in Sensory Neurons in a Model of Generalized Pain J. Neurosci., May 28, 2008; 28(22): 5721 - 5730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Limer, B. I. Nicholl, W. Thomson, and J. McBeth Exploring the genetic susceptibility of chronic widespread pain: the tender points in genetic association studies Rheumatology, May 1, 2008; 47(5): 572 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nikoshkov, K. Drakenberg, X. Wang, M. Cs. Horvath, E. Keller, and Y. L. Hurd Opioid neuropeptide genotypes in relation to heroin abuse: Dopamine tone contributes to reversed mesolimbic proenkephalin expression PNAS, January 15, 2008; 105(2): 786 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.D. Slade, L. Diatchenko, K. Bhalang, A. Sigurdsson, R.B. Fillingim, I. Belfer, M.B. Max, D. Goldman, and W. Maixner Influence of Psychological Factors on Risk of Temporomandibular Disorders Journal of Dental Research, November 1, 2007; 86(11): 1120 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Norbury, A. J. MacGregor, J. Urwin, T. D. Spector, and S. B. McMahon Heritability of responses to painful stimuli in women: a classical twin study Brain, November 1, 2007; 130(11): 3041 - 3049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Klasser and C. S. Greene Authors' response J Am Dent Assoc, June 1, 2007; 138(6): 712 - 713. [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Reuben and A. Buvanendran Preventing the Development of Chronic Pain After Orthopaedic Surgery with Preventive Multimodal Analgesic Techniques J. Bone Joint Surg. Am., June 1, 2007; 89(6): 1343 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ross Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 857 - 858. [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Nackley, S. A. Shabalina, I. E. Tchivileva, K. Satterfield, O. Korchynskyi, S. S. Makarov, W. Maixner, and L. Diatchenko Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure Science, December 22, 2006; 314(5807): 1930 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Schikler Potential Polygenic Influences on Chronic Fatigue Syndrome Pediatrics, October 1, 2006; 118(4): 1799 - 1800. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Goldman, G. Oroszi, and F. Ducci The Genetics of Addictions: Uncovering the Genes Focus, August 1, 2006; 4(3): 401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Kim, D P Mittal, M J Iadarola, and R A Dionne Genetic predictors for acute experimental cold and heat pain sensitivity in humans. J. Med. Genet., August 1, 2006; 43(8): e40 - e40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Ross, J. Riley, C. Quigley, and K. I. Welsh Clinical Pharmacology and Pharmacotherapy of Opioid Switching in Cancer Patients Oncologist, July 1, 2006; 11(7): 765 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Pemberton, J. Gee, and P. I. Patel Gene discovery for dental anomalies: A primer for the dental professional. J Am Dent Assoc, June 1, 2006; 137(6): 743 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. R. Smith, C. S. Stohler, T. E. Nichols, J. A. Bueller, R. A. Koeppe, and J.-K. Zubieta Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women J. Neurosci., May 24, 2006; 26(21): 5777 - 5785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Sellers, J. M. Schildkraut, V. S. Pankratz, R. A. Vierkant, Z. S. Fredericksen, J. E. Olson, J. Cunningham, W. Taylor, M. Liebow, C. McPherson, et al. Estrogen Bioactivation, Genetic Polymorphisms, and Ovarian Cancer Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2536 - 2543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Edwards Individual differences in endogenous pain modulation as a risk factor for chronic pain Neurology, August 9, 2005; 65(3): 437 - 443. [Abstract] [Full Text] [PDF]
|
|