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Pain-related single nucleotide polymorphisms: association with lumbar spinal stenosis patient experience and non-surgical treatment outcomes

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Abstract

Purpose

Lumbar spinal stenosis (LSS) is common in our aging population resulting in pain and functional impairment. Recent advances in pain research have identified several single nucleotide polymorphisms (SNP) associated with inter-individual symptom and treatment response. The goal of the current study was to investigate the association of SNPs in Neuropeptide Y (NPY) and Catechol-O-methyltransferase (COMT) with pain, function, and treatment outcomes in Lumbar spinal stenosis (LSS) patients receiving non-surgical treatments.

Methods

An exploratory observational biomarker study was performed ancillary to a previously published clinical trial evaluating three different non-surgical treatments for LSS. Saliva samples were obtained for single nucleotide polymorphism genotyping and blood samples were collected for NPY protein. Data on pain and function collected as part of the clinical trial at baseline, 2 and 6 months were examined for association with known polymorphisms in NPY and COMT.

Results

Subjects with the NPY rs16147 TT genotype exhibited higher baseline symptom severity but also a higher likelihood of responding to non-surgical treatments. Subjects with the COMT rs4680 GG genotype also exhibited higher baseline symptom severity but did not demonstrate greater response to treatment.

Conclusions

NPY rs16147 and COMT rs4680 are important potential biomarkers associated with pain and function. NPY genotype may be useful in predicting response to non-surgical treatments in older adults with LSS.

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References

  1. Zhou Z, Zhu G, Hariri AR, Enoch MA, Scott D, Sinha R, Virkkunen M, Mash DC, Lipsky RH, Hu XZ, Hodgkinson CA, Xu K, Buzas B, Yuan Q, Shen PH, Ferrell RE, Manuck SB, Brown SM, Hauger RL, Stohler CS, Zubieta JK, Goldman D (2008) Genetic variation in human NPY expression affects stress response and emotion. Nature 452:997–1001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mickey BJ, Zhou Z, Heitzeg MM, Heinz E, Hodgkinson CA, Hsu DT, Langenecker SA, Love TM, Pecina M, Shafir T, Stohler CS, Goldman D, Zubieta JK (2011) Emotion processing, major depression, and functional genetic variation of neuropeptide Y. Arch Gen Psychiatry 68:158–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Belfer I, Segall S (2011) COMT genetic variants and pain. Drugs Today (Barc) 47:457–467

    Article  CAS  PubMed  Google Scholar 

  4. George SZ, Parr JJ, Wallace MR, Wu SS, Borsa PA, Dai Y, Fillingim RB (2014) Biopsychosocial influence on exercise-induced injury: genetic and psychological combinations are predictive of shoulder pain phenotypes. J Pain 15:68–80

    Article  PubMed  Google Scholar 

  5. Schneider MJ, Ammendolia C, Murphy DR, Glick RM, Hile E, Tudorascu DL, Morton SC, Smith C, Patterson CG, Piva SR (2019) Comparative clinical effectiveness of nonsurgical treatment methods in patients with lumbar spinal stenosis: a randomized clinical trial. JAMA Netw Open 2:e186828

    Article  PubMed  PubMed Central  Google Scholar 

  6. Stucki G, Daltroy L, Liang MH, Lipson SJ, Fossel AH, Katz JN (1996) Measurement properties of a self-administered outcome measure in lumbar spinal stenosis. Spine (Phila Pa 1976) 21:796–803

    Article  CAS  PubMed  Google Scholar 

  7. Tomkins-Lane CC, Battie MC (2010) Validity and reproducibility of self-report measures of walking capacity in lumbar spinal stenosis. Spine (Phila Pa 1976) 35:2097–2102

    Article  PubMed  Google Scholar 

  8. Sommer WH, Lidstrom J, Sun H, Passer D, Eskay R, Parker SC, Witt SH, Zimmermann US, Nieratschker V, Rietschel M, Margulies EH, Palkovits M, Laucht M, Heilig M (2010) Human NPY promoter variation rs16147:T>C as a moderator of prefrontal NPY gene expression and negative affect. Hum Mutat 31:E1594-1608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shah SH, Freedman NJ, Zhang L, Crosslin DR, Stone DH, Haynes C, Johnson J, Nelson S, Wang L, Connelly JJ, Muehlbauer M, Ginsburg GS, Crossman DC, Jones CJ, Vance J, Sketch MH, Granger CB, Newgard CB, Gregory SG, Goldschmidt-Clermont PJ, Kraus WE, Hauser ER (2009) Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis. PLoS Genet 5:e1000318

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cleland JA, Whitman JM, Houser JL, Wainner RS, Childs JD (2012) Psychometric properties of selected tests in patients with lumbar spinal stenosis. Spine J 12:921–931

    Article  PubMed  Google Scholar 

  11. Diaz-delCastillo M, Woldbye DPD, Heegaard AM (2018) Neuropeptide Y and its involvement in chronic pain. Neuroscience 387:162–169

    Article  CAS  PubMed  Google Scholar 

  12. Sowa GA, Perera S, Bechara B, Agarwal V, Boardman J, Huang W, Camacho-Soto A, Vo N, Kang J, Weiner D (2014) Associations between serum biomarkers and pain and pain-related function in older adults with low back pain: a pilot study. J Am Geriatr Soc 62:2047–2055

    Article  PubMed  Google Scholar 

  13. Mier D, Kirsch P, Meyer-Lindenberg A (2010) Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Mol Psychiatry 15:918–927

    Article  CAS  PubMed  Google Scholar 

  14. Andersen S, Skorpen F (2009) Variation in the COMT gene: implications for pain perception and pain treatment. Pharmacogenomics 10:669–684

    Article  CAS  PubMed  Google Scholar 

  15. 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 67:468–472

    Article  CAS  PubMed  Google Scholar 

  16. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, Goldman D (2003) COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 299:1240–1243

    Article  CAS  PubMed  Google Scholar 

  17. Jacobsen LM, Eriksen GS, Pedersen LM, Gjerstad J (2010) Catechol-O-methyltransferase (COMT) inhibition reduces spinal nociceptive activity. Neurosci Lett 473:212–215

    Article  CAS  PubMed  Google Scholar 

  18. 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 16:1064–1069

    Article  CAS  PubMed  Google Scholar 

  19. Schaaf S, Huang W, Perera S, Conley Y, Belfer I, Jayabalan P, Tremont K, Coelho P, Ernst S, Cortazzo M, Weiner D, Vo N, Kang J, Sowa G (2021) Association of protein and genetic biomarkers with response to lumbar epidural steroid injections in subjects with axial low back pain. Am J Phys Med Rehab 100:48–56

    Article  Google Scholar 

  20. 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 Musculoskelet Disord 13:76

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Authors would like to thank the members of Ferguson Laboratory for Orthopedic Research for their valuable support.

Funding

Foundation for Physical Medicine and Rehabilitation, Gwendolyn Sowa, Patient-Centered Outcomes Research Institute, CER-1410-25056, Michael Schneider

Author information

Authors and Affiliations

  1. Department of Physical Medicine & Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Sara Ernst, Wan Huang & Gwendolyn Sowa

  2. Department of Orthopaedic Surgery School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Nam Vo

  3. Ferguson Laboratory for Orthopedic and Spine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Wan Huang, Nam Vo & Gwendolyn Sowa

  4. Department of Nursing, University of Pittsburgh, Pittsburgh, PA, USA

    Yvette Conley

  5. School of Health and Rehabilitation Sciences, Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA, USA

    Michael Schneider

  6. Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Michael Schneider

Authors
  1. Sara Ernst
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  2. Wan Huang
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  3. Yvette Conley
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  4. Nam Vo
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  5. Michael Schneider
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  6. Gwendolyn Sowa
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Correspondence to Gwendolyn Sowa.

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Ernst, S., Huang, W., Conley, Y. et al. Pain-related single nucleotide polymorphisms: association with lumbar spinal stenosis patient experience and non-surgical treatment outcomes. Eur Spine J (2024). https://doi.org/10.1007/s00586-024-08182-0

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  • DOI: https://doi.org/10.1007/s00586-024-08182-0

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