DOLORisk: study protocol for a multi-centre observational study to understand the risk factors and determinants of neuropathic pain

Mathilde M V Pascal, Andreas C Themistocleous, Ralf Baron, Andreas Binder, Didier Bouhassira, Geert Crombez, Nanna B Finnerup, Janne Gierthmühlen, Yelena Granovsky, Leif Groop, Harry L Hebert, Troels S Jensen, Kristinn Johnsen, Mark I McCarthy, Weihua Meng, Colin N A Palmer, Andrew S C Rice, Jordi Serra, Romà Solà, David Yarnitsky, Blair H Smith, Nadine Attal, David L H Bennett, Mathilde M V Pascal, Andreas C Themistocleous, Ralf Baron, Andreas Binder, Didier Bouhassira, Geert Crombez, Nanna B Finnerup, Janne Gierthmühlen, Yelena Granovsky, Leif Groop, Harry L Hebert, Troels S Jensen, Kristinn Johnsen, Mark I McCarthy, Weihua Meng, Colin N A Palmer, Andrew S C Rice, Jordi Serra, Romà Solà, David Yarnitsky, Blair H Smith, Nadine Attal, David L H Bennett

Abstract

Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in large cohorts. The DOLORisk study aims to study these factors. Protocol: Multicentre cross-sectional and longitudinal cohorts covering the main causes leading to neuropathic pain (e.g. diabetes, surgery, chemotherapy, traumatic injury), as well as rare conditions, follow a common protocol for phenotyping of the participants. This core protocol correlates answers given by the participants on a set of questionnaires with the results of their genetic analyses. A smaller number of participants undergo deeper phenotyping procedures, including neurological examination, nerve conduction studies, threshold tracking, quantitative sensory testing, conditioned pain modulation and electroencephalography. Ethics and dissemination: All studies have been approved by their regional ethics committees as required by national law. Results are disseminated through the DOLORisk website, scientific meetings, open-access publications, and in partnership with patient organisations. Strengths and limitations: Large cohorts covering many possible triggers for neuropathic painMulti-disciplinary approach to study the interaction of clinical, psychosocial and genetic risk factorsHigh comparability of the data across centres thanks to harmonised protocolsOne limitation is that the length of the questionnaires might reduce the response rate and quality of responses of participants.

Keywords: diabetes; nerve injury; neuropathic pain; neuropathy; pain; protocol; risk factors.

Conflict of interest statement

Competing interests: DLB has acted as a consultant on behalf of Oxford Innovation for Abide, Biogen, GSK, Lilly, Mitsubishi Tanabe, Mundipharma and TEVA over the last 3 years. NA received speaker honoraria from Pfizer and reported fees for consultant services from Novartis, Teva, Grünenthal, Mundipharma, Sanofi Pasteur, Aptinyx. ASCR has received funding from Orion Pharma. ASCR undertakes consultancy and advisory board work for Imperial College Consultants—in the past 12 months, this has included remunerated work for: Merck, Galapagos, Toray, Quartet, Lateral, Novartis and Orion. ASCR was the owner of share options in Spinifex Pharmaceuticals from which personal benefit accrued on the acquisition of Spinifex by Novartis in July 2015 and from which future milestone payments may occur. ASCR is named as an inventor on patents: Rice A.S.C., Vandevoorde S. and Lambert D.M Methods using N-(2-propenyl)hexadecanamide and related amides to relieve pain, WO 2005/079771 (Google Patents); Okuse K. et al Methods of treating pain by inhibition of vgf activity, EP13702262.0/WO2013 110945 (Google Patents).

Figures

Figure 1.. DOLORisk Recruitment flow.
Figure 1.. DOLORisk Recruitment flow.
DK = Denmark, FR = France.

References

    1. van Hecke O, Austin SK, Khan RA, et al. : Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654–62. 10.1016/j.pain.2013.11.013
    1. Attal N, Lanteri-Minet M, Laurent B, et al. : The specific disease burden of neuropathic pain: results of a French nationwide survey. Pain. 2011;152(12):2836–43. 10.1016/j.pain.2011.09.014
    1. Finnerup NB, Sindrup SH, Jensen TS: The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150(3):573–81. 10.1016/j.pain.2010.06.019
    1. Treede RD, Jensen TS, Campbell JN, et al. : Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70(18):1630–5. 10.1212/01.wnl.0000282763.29778.59
    1. Themistocleous AC, Ramirez JD, Shillo PR, et al. : The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy. Pain. 2016;157(5):1132–45. 10.1097/j.pain.0000000000000491
    1. von Hehn CA, Baron R, Woolf CJ: Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012;73(4):638–52. 10.1016/j.neuron.2012.02.008
    1. Denk F, McMahon SB, Tracey I: Pain vulnerability: a neurobiological perspective. Nat Neurosci. 2014;17(2):192–200. 10.1038/nn.3628
    1. Denk F, McMahon SB: Neurobiological basis for pain vulnerability: why me? Pain. 2017;158 Suppl 1:S108–S14. 10.1097/j.pain.0000000000000858
    1. Bouhassira D, Attal N, Alchaar H, et al. : Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005;114(1–2):29–36. 10.1016/j.pain.2004.12.010
    1. Freynhagen R, Baron R, Gockel U, et al. : pain DETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006;22(10):1911–20. 10.1185/030079906X132488
    1. Rolke R, Baron R, Maier C, et al. : Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–43. 10.1016/j.pain.2006.01.041
    1. Bennett MI, Smith BH, Torrance N, et al. : The S-LANSS score for identifying pain of predominantly neuropathic origin: validation for use in clinical and postal research. J Pain. 2005;6(3):149–58. 10.1016/j.jpain.2004.11.007
    1. Haanpää M, Attal N, Backonja M, et al. : NeuPSIG guidelines on neuropathic pain assessment. Pain. 2011;152(1):14–27. 10.1016/j.pain.2010.07.031
    1. van Hecke O, Kamerman PR, Attal N, et al. : Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations. Pain. 2015;156(11):2337–53. 10.1097/j.pain.0000000000000335
    1. Cleeland CS, Ryan KM: Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23(2):129–38.
    1. Von Korff M, Ormel J, Keefe FJ, et al. : Grading the severity of chronic pain. Pain. 1992;50(2):133–49. 10.1016/0304-3959(92)90154-4
    1. Bouhassira D, Attal N, Fermanian J, et al. : Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004;108(3):248–57. 10.1016/j.pain.2003.12.024
    1. Feldman EL, Stevens MJ, Thomas PK, et al. : A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care. 1994;17(11):1281–9. 10.2337/diacare.17.11.1281
    1. Cella D, Riley W, Stone A, et al. : The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010;63(11):1179–94. 10.1016/j.jclinepi.2010.04.011
    1. Sullivan MJL, Bishop SR, Pivik J: The Pain Catastrophizing Scale: Development and validation. Psychol Assess. 1995;7(4):524–32. 10.1037/1040-3590.7.4.524
    1. Herdman M, Gudex C, Lloyd A, et al. : Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727–36. 10.1007/s11136-011-9903-x
    1. Gosling SD, Rentfrow PJ, Swann WB: A very brief measure of the Big-Five personality domains. J Res Pers. 2003;37(6):504–28. 10.1016/S0092-6566(03)00046-1
    1. Goldberg LR: A broad-bandwidth, public domain, personality inventory measuring the lower-level facets of several five-factor models.
    1. Campbell A, Kerr SM, Porteous DJ: Generation Scotland SFHS Data Dictionary, 2006-2011. University of Edinburgh. School of Molecular, Genetic and Population Health Sciences. Institute of Genetics and Molecular Medicine,2018. 10.7488/ds/2277
    1. Craig CL, Marshall AL, Sjöström M, et al. : International physical activity questionnaire: 12-country reliability and validity. Med Sci Sport Exer. 2003;35(8):1381–95. 10.1249/01.MSS.0000078924.61453.FB
    1. Finnerup NB, Haroutounian S, Kamerman P, et al. : Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016;157(8):1599–606. 10.1097/j.pain.0000000000000492
    1. Goldberg LR: The development of markers for the Big-Five factor structure. Psychol Assess. 1992;4(1):26–42. 10.1037/1040-3590.4.1.26
    1. Kleyweg RP, van der Meché FG, Schmitz PI: Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome. Muscle Nerve. 1991;14(11):1103–09. 10.1002/mus.880141111
    1. Medical Research Council - Nerve Injuries Research Committee: Aids to the examination of the peripheral nervous system. Fifth Edition ed: Saunders Elsevier on behalf of Guarantors of Brain. 2010.
    1. Phillips TJ, Brown M, Ramirez JD, et al. : Sensory, psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: A cross-sectional deep profiling study. Pain. 2014;155(9):1846–60. 10.1016/j.pain.2014.06.014
    1. Bril V, Perkins BA: Validation of the Toronto Clinical Scoring System for diabetic polyneuropathy. Diabetes Care. 2002;25(11):2048–52. 10.2337/diacare.25.11.2048
    1. Smith EM, Cohen JA, Pett MA, et al. : The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums. Cancer Nurs. 2010;33(3):173–83. 10.1097/NCC.0b013e3181c989a3
    1. Buschbacher R, Orahlow N: Manual of nerve conduction studies. Second edition ed. New York, New York: Demos Medical Publishing.2006.
    1. England JD, Gronseth GS, Franklin G, et al. : Distal symmetric polyneuropathy: a definition for clinical research: report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2005;64(2):199–207. 10.1212/01.WNL.0000149522.32823.EA
    1. Nir RR, Sinai A, Raz E, et al. : Pain assessment by continuous EEG: association between subjective perception of tonic pain and peak frequency of alpha oscillations during stimulation and at rest. Brain Res. 2010;1344:77–86. 10.1016/j.brainres.2010.05.004
    1. Furman AJ, Meeker TJ, Rietschel JC, et al. : Cerebral peak alpha frequency predicts individual differences in pain sensitivity. NeuroImage. 2018;167:203–210. 10.1016/j.neuroimage.2017.11.042
    1. Z'Graggen WJ, Bostock H: Nerve membrane excitability testing. Eur J Anaesthesiol Suppl. 2008;42:68–72. 10.1017/S0265021508003505
    1. Kiernan MC, Burke D, Andersen KV, et al. : Multiple measures of axonal excitability: a new approach in clinical testing. Muscle Nerve. 2000;23(3):399–409. 10.1002/(SICI)1097-4598(200003)23:3<399::AID-MUS12>;2-G
    1. Lauria G, Hsieh ST, Johansson O, et al. : European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010;17(7):903–12, e44–9. 10.1111/j.1468-1331.2010.03023.x
    1. Rolke R, Baron R, Maier C, et al. : Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–43. 10.1016/j.pain.2006.01.041
    1. Magerl W, Krumova EK, Baron R, et al. : Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data. Pain. 2010;151(3):598–605. 10.1016/j.pain.2010.07.026
    1. Rolke R, Magerl W, Campbell KA, et al. : Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006;10(1):77–88. 10.1016/j.ejpain.2005.02.003
    1. Yarnitsky D: Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol. 2010;23(5):611–5. 10.1097/ACO.0b013e32833c348b
    1. Yarnitsky D, Granot M, Nahman-Averbuch H, et al. : Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain. 2012;153(6):1193–8. 10.1016/j.pain.2012.02.021
    1. Yarnitsky D, Arendt-Nielsen L, Bouhassira D, et al. : Recommendations on terminology and practice of psychophysical DNIC testing. Eur J Pain. 2010;14(4):339. 10.1016/j.ejpain.2010.02.004
    1. Yarnitsky D, Bouhassira D, Drewes AM, et al. : Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain. 2015;19(6):805–6. 10.1002/ejp.605
    1. Tesfaye S, Boulton AJ, Dyck PJ, et al. : Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285–93. 10.2337/dc10-1303
    1. Finnerup NB, Haroutounian S, Kamerman P, et al. : Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016;157(8):1599–606. 10.1097/j.pain.0000000000000492
    1. Smith BH, Campbell A, Linksted P, et al. : Cohort Profile: Generation Scotland: Scottish Family Health Study (GS:SFHS). The study, its participants and their potential for genetic research on health and illness. Int J Epidemiol. 2013;42(3):689–700. 10.1093/ije/dys084
    1. Hébert HL, Shepherd B, Milburn K, et al. : Cohort Profile: Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS). Int J Epidemiol. 2018;47(2):380–381j. 10.1093/ije/dyx140
    1. Torrance N, Ferguson JA, Afolabi E, et al. : Neuropathic pain in the community: more under-treated than refractory? Pain. 2013;154(5):690–99. 10.1016/j.pain.2012.12.022
    1. Skol AD, Scott LJ, Abecasis GR, et al. : Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet. 2006;38(2):209–13. 10.1038/ng1706
    1. Perkins JR, Lees J, Antunes-Martins A, et al. : PainNetworks: a web-based resource for the visualisation of pain-related genes in the context of their network associations. Pain. 2013;154(12):2586.e1–12. 10.1016/j.pain.2013.09.003

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