European Spine Journal

, Volume 24, Issue 11, pp 2425–2431 | Cite as

Catechol-O-methyltransferase (COMT) gene polymorphisms are associated with baseline disability but not long-term treatment outcome in patients with chronic low back pain

  • Ahmad OmairEmail author
  • Anne F. Mannion
  • Marit Holden
  • Jeremy Fairbank
  • Benedicte A. Lie
  • Olle Hägg
  • Peter Fritzell
  • Jens I. Brox
Original Article



To examine the association between COMT and OPRM1 gene polymorphisms and pain and disability at baseline and long-term follow-up in patients treated for chronic low back pain (LBP).


371 of 767 unrelated European patients recruited from four randomised trials underwent genetic analyses at mean 11.4 years follow-up. 274 patients had fusion and 97 had non-operative treatment. Association analyses included disability, pain, five single nucleotide polymorphisms (SNPs) in the COMT gene, and one SNP in the OPRM1 gene. Analyses were adjusted for age, gender, smoking, analgesics and treatment.


Disability at baseline was significantly associated with COMT SNPs rs4818 (p = 0.02), rs6269 (p = 0.007), rs4633 (p = 0.04) rs2075507 (p = 0.009), two haplotypes (p < 0.002), age, gender and smoking (p ≤ 0.002). No significant associations with clinical variables were observed for OPRM1, or for COMT at long-term follow-up.


Results suggest that genetic factors are partly responsible for the variation in disability levels in patients presenting with chronic LBP being considered for surgery; in contrast, genetics has no influence on the long-term outcome of treatment.


Chronic low back pain Lumbar fusion Catechol-O-methyltransferase Single nucleotide polymorphism Pain perception Modulation 



We thank department of Immunology Oslo University Hospital-Rikshospitalet (IMMI), for providing us with the logistics for DNA purification and the Center for Interactive Genetics, Norwegian University of Life Sciences (UMB) Aas, for performing Sequenom analysis. AO Spine funds were received via the Hansjorg Wyss Research Award. In the UK, the study was also supported by Thames Valley Comprehensive Local Research Network for National Institutes for Health Research. In Norway, the Norwegian Research Council grant funds were received to support this work. We thank them for providing the financial support.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    MacGregor AJ, Andrew T, Sambrook PN, Spector TD (2004) Structural, psychological, and genetic influences on low back and neck pain: a study of adult female twins. Arthritis Rheum 51:160–167CrossRefPubMedGoogle Scholar
  2. 2.
    Diatchenko L, Nackley AG, Slade GD, Bhalang K, Belfer I, Max MB, Goldman D, Maixner W (2006) Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain 125:216–224CrossRefPubMedGoogle Scholar
  3. 3.
    Fillingim RB, Kaplan L, Staud R, Ness TJ, Glover TL, Campbell CM, Mogil JS, Wallace MR (2005) The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans. J Pain 6:159–167CrossRefPubMedGoogle Scholar
  4. 4.
    Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lotsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ (2006) GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 12:1269–1277CrossRefPubMedGoogle Scholar
  5. 5.
    Dai F, Belfer I, Schwartz CE, Banco R, Martha JF, Tighioughart H, Tromanhauser SG, Jenis LG, Kim DH (2010) Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease. Spine J 10:949–957CrossRefPubMedGoogle Scholar
  6. 6.
    Olsen MB, Jacobsen LM, Schistad EI, Pedersen LM, Rygh LJ, Roe C, Gjerstad J (2012) Pain intensity the first year after lumbar disc herniation is associated with the A118G polymorphism in the opioid receptor mu 1 gene: evidence of a sex and genotype interaction. J Neurosci Off J Soc Neurosci 32:9831–9834CrossRefGoogle Scholar
  7. 7.
    Omair A, Lie BA, Reikeras O, Holden M, Brox JI (2012) Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic association study. BMC Musculoskelt Disord 13:76CrossRefGoogle Scholar
  8. 8.
    Andersen S, Skorpen F (2009) Variation in the COMT gene: implications for pain perception and pain treatment. Pharmacogenomics 10:669–684CrossRefPubMedGoogle Scholar
  9. 9.
    Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W (2005) Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 14:135–143CrossRefPubMedGoogle Scholar
  10. 10.
    Lachman HM, Morrow B, Shprintzen R, Veit S, Parsia SS, Faedda G, Goldberg R, Kucherlapati R, Papolos DF (1996) Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. Am J Med Genet 67:468–472CrossRefPubMedGoogle Scholar
  11. 11.
    Jacobsen LM, Schistad EI, Storesund A, Pedersen LM, Rygh LJ, Roe C, Gjerstad J (2012) The COMT rs4680 Met allele contributes to long-lasting low back pain, sciatica and disability after lumbar disc herniation. Eur J Pain 16:1064–1069CrossRefPubMedGoogle Scholar
  12. 12.
    Menon S, Lea RA, Roy B, Hanna M, Wee S, Haupt LM, Griffiths LR (2012) The human mu-opioid receptor gene polymorphism (A118G) is associated with head pain severity in a clinical cohort of female migraine with aura patients. J Headache Pain 13:513–519PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Brox JI, Reikeras O, Nygaard O, Sorensen R, Indahl A, Holm I, Keller A, Ingebrigtsen T, Grundnes O, Lange JE, Friis A (2006) Lumbar instrumented fusion compared with cognitive intervention and exercises in patients with chronic back pain after previous surgery for disc herniation: a prospective randomized controlled study. Pain 122:145–155CrossRefPubMedGoogle Scholar
  14. 14.
    Brox JI, Sorensen R, Friis A, Nygaard O, Indahl A, Keller A, Ingebrigtsen T, Eriksen HR, Holm I, Koller AK, Riise R, Reikeras O (2003) Randomized clinical trial of lumbar instrumented fusion and cognitive intervention and exercises in patients with chronic low back pain and disc degeneration. Spine 28:1913–1921CrossRefPubMedGoogle Scholar
  15. 15.
    Fairbank J, Frost H, Wilson-MacDonald J, Yu LM, Barker K, Collins R (2005) Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial. BMJ 330:1233PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Fritzell P, Hagg O, Wessberg P, Nordwall A (2001) 2001 Volvo award winner in clinical studies: lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish lumbar spine study group. Spine 26:2521–2532 (discussion 2532–2534)CrossRefPubMedGoogle Scholar
  17. 17.
    Fairbank JC, Pynsent PB (2000) The Oswestry disability index. Spine 25:2940–2952 (discussion 2952)CrossRefPubMedGoogle Scholar
  18. 18.
    Omair A, Holden M, Lie BA, Reikeras O, Brox JI (2013) Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants: a prospective genetic association study. BMC Musculoskelet Disord 14:105PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA (2002) Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 70:425–434PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Lee PJ, Delaney P, Keogh J, Sleeman D, Shorten GD (2011) Catecholamine-O-methyltransferase polymorphisms are associated with postoperative pain intensity. Clin J Pain 27:93–101CrossRefPubMedGoogle Scholar
  21. 21.
    Rakvag TT, Ross JR, Sato H, Skorpen F, Kaasa S, Klepstad P (2008) Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol Pain 4:64PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Barbosa FR, Matsuda JB, Mazucato M, de Castro Franca S, Zingaretti SM, da Silva LM, Martinez-Rossi NM, Junior MF, Marins M, Fachin AL (2012) Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients. Rheumatol Int 32:427–430CrossRefPubMedGoogle Scholar
  23. 23.
    Vargas-Alarcon G, Fragoso JM, Cruz-Robles D, Vargas A, Lao-Villadoniga JI, Garcia-Fructuoso F, Ramos-Kuri M, Hernandez F, Springall R, Bojalil R, Vallejo M, Martinez-Lavin M (2007) Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis Res Ther 9:R110PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Ross JR, Riley J, Taegetmeyer AB, Sato H, Gretton S, du Bois RM, Welsh KI (2008) Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects. Cancer 112:1390–1403CrossRefPubMedGoogle Scholar
  25. 25.
    Hagen K, Pettersen E, Stovner LJ, Skorpen F, Zwart JA (2006) No association between chronic musculoskeletal complaints and Val158Met polymorphism in the catechol-O-methyltransferase gene. The HUNT study. BMC Musculoskelet Disord 7:40PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Johnsen LG, Hellum C, Nygaard OP, Storheim K, Brox JI, Rossvoll I, Leivseth G, Grotle M (2013) Comparison of the SF6D, the EQ5D, and the oswestry disability index in patients with chronic low back pain and degenerative disc disease. BMC Musculoskelet Disord 14:148PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ahmad Omair
    • 1
    • 9
    Email author
  • Anne F. Mannion
    • 2
  • Marit Holden
    • 3
  • Jeremy Fairbank
    • 4
  • Benedicte A. Lie
    • 5
  • Olle Hägg
    • 6
  • Peter Fritzell
    • 7
  • Jens I. Brox
    • 8
  1. 1.Department of OrthopaedicsOslo University Hospital-RikshospitaletOsloNorway
  2. 2.Department of Research and Development, Spine Center DivisionSchulthess KlinikZurichSwitzerland
  3. 3.Norwegian Computing CentreOsloNorway
  4. 4.Nuffield Orthopaedic CentreUniversity of OxfordOxfordUK
  5. 5.Department of Medical GeneticsUniversity of Oslo and Oslo University Hospital-UllevålOsloNorway
  6. 6.Spine Center GöteborgGothenburgSweden
  7. 7.Neuro-ortopedic CenterLänssjukhuset RyhovJönköpingSweden
  8. 8.Department of Physical Medicine and RehabilitationOslo University Hospital, University of OsloOsloNorway
  9. 9.Department of PathologyShifa College of MedicineIslamabadPakistan

Personalised recommendations