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Sensory Profiles and Diabetic Neuropathy

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Diabetic Neuropathy

Part of the book series: Contemporary Diabetes ((CDI))

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Abstract

Treatment of neuropathic pain in general, and in diabetic neuropathy in particular, often results in inadequate pain relief, even with first-line drugs. New therapeutic approaches are therefore mechanism-based targeting the individual pathophysiological pain mechanisms. The sensory phenotype of a patient, i.e., the sensory signs and symptoms, can provide indirect information about these underlying pathomechanisms. Quantitative sensory testing (QST) can be used to assess the function of the large and small nerve fibers or the corresponding central pathways to generate an individual sensory profile with loss and gain of function parameters for each patient. Stratification of patients according to these profiles can help to identify subgroups of patients with similar pathophysiological mechanisms. In diabetic neuropathy the most frequent subgroup is dominated by a loss of small and large fiber function with little or no gain of function (deafferentation/sensory loss cluster). A similar approach relates to individual patient symptoms using patient reported outcome measures, i.e., neuropathic pain specific questionnaires. This phenotypic-based subgrouping has proven to be a promising approach to prospectively identify responders to a certain therapy, potentially realizing the concept of a new, individualized mechanism-based pain therapy.

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References

  1. Sloan G, et al. A new look at painful diabetic neuropathy. Diabetes Res Clin Pract. 2018;144:177–91. https://doi.org/10.1016/j.diabres.2018.08.020.

    Article  PubMed  Google Scholar 

  2. Attal N, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113. https://doi.org/10.1111/j.1468-1331.2010.02999.x.

    Article  CAS  PubMed  Google Scholar 

  3. Finnerup NB, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–73. https://doi.org/10.1016/S1474-4422(14)70251-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bril V, et al. Evidence-based guideline: treatment of painful diabetic neuropathy–report of the American Association of Neuromuscular and Electrodiagnostic Medicine, the American Academy of Neurology, and the American Academy of Physical Medicine & Rehabilitation. Muscle Nerve. 2011;43(6):910–7. https://doi.org/10.1002/mus.22092.

    Article  PubMed  Google Scholar 

  5. Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med. 2004;21(9):976–82. https://doi.org/10.1111/j.1464-5491.2004.01271.x.

    Article  CAS  PubMed  Google Scholar 

  6. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012;73(4):638–52. https://doi.org/10.1016/j.neuron.2012.02.008.

    Article  CAS  Google Scholar 

  7. LaMotte RH, Thalhammer JG, Torebjörk HE, Robinson CJ. Peripheral neural mechanisms of cutaneous hyperalgesia following mild injury by heat. J Neurosci. 1982;2(6):765–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. LaMotte RH, Shain CN, Simone DA, Tsai EF. Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. J Neurophysiol. 1991;66(1):190–211. https://doi.org/10.1152/jn.1991.66.1.190.

    Article  CAS  PubMed  Google Scholar 

  9. Fruhstorfer H. Thermal sensibility changes during ischemic nerve block. Pain. 1984;20(4):355–61. https://doi.org/10.1016/0304-3959(84)90112-X.

    Article  PubMed  Google Scholar 

  10. Yarnitsky D, Ochoa JL. Differential effect of compression-ischaemia block on warm sensation and heat-induced pain. Brain. 1991;114(2):907–13. https://doi.org/10.1093/brain/114.2.907.

    Article  PubMed  Google Scholar 

  11. Ziegler EA, Magerl W, Meyer RA, Treede RD. Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. Brain. 1999;122(12):2245–57. https://doi.org/10.1093/brain/122.12.2245.

    Article  PubMed  Google Scholar 

  12. Geber C, et al. Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): a multi-centre study. Pain. 2011;152(3):548–56. https://doi.org/10.1016/j.pain.2010.11.013.

    Article  PubMed  Google Scholar 

  13. Vollert J, et al. Quantitative sensory testing using DFNS protocol in Europe: an evaluation of heterogeneity across multiple centers in patients with peripheral neuropathic pain and healthy subjects. Pain. 2016;157(3):750–8. https://doi.org/10.1097/j.pain.0000000000000433.

    Article  PubMed  Google Scholar 

  14. Rolke R, 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. https://doi.org/10.1016/j.pain.2006.01.041.

    Article  CAS  PubMed  Google Scholar 

  15. Rolke R, et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006;10(1):77–88. https://doi.org/10.1016/j.ejpain.2005.02.003.

    Article  CAS  PubMed  Google Scholar 

  16. Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain. 2010;150(3):439–50. https://doi.org/10.1016/j.pain.2010.05.002.

    Article  CAS  PubMed  Google Scholar 

  17. Treede R-D. Chapter 1 pain and hyperalgesia: definitions and theories. Handb Clin Neurol. 2006;81:3–10. https://doi.org/10.1016/S0072-9752(06)80005-9.

    Article  PubMed  Google Scholar 

  18. Obata K, et al. TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury. J Clin Invest. 2005;115(9):2393–401. https://doi.org/10.1172/JCI25437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fruhstorfer H, Gross W, Selbmann O. von Frey hairs: new materials for a new design. Eur J Pain. 2001;5(3):341–2. https://doi.org/10.1053/eujp.2001.0250.

    Article  CAS  PubMed  Google Scholar 

  20. Herrero JF, Laird JM, López-García JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol. 2000;61(2):169–203. https://doi.org/10.1016/s0301-0082(99)00051-9.

    Article  CAS  PubMed  Google Scholar 

  21. Glass GV, Stanley JX. Statistical methods in education and psychology. Englewood Cliffs: Prentice-Hall; 1970.

    Google Scholar 

  22. Blankenburg M, et al. Reference values for quantitative sensory testing in children and adolescents: developmental and gender differences of somatosensory perception. Pain. 2010;149(1):76–88. https://doi.org/10.1016/j.pain.2010.01.011.

    Article  CAS  PubMed  Google Scholar 

  23. Pfau DB, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia. Pain. 2014;155(5):1002–15. https://doi.org/10.1016/j.pain.2014.02.004.

    Article  PubMed  Google Scholar 

  24. Gierthmühlen J, et al. Who is healthy? Aspects to consider when including healthy volunteers in QST--based studies-a consensus statement by the EUROPAIN and NEUROPAIN consortia. Pain. 2015;156(11):2203–11. https://doi.org/10.1097/j.pain.0000000000000227.

    Article  PubMed  Google Scholar 

  25. Smith SM, et al. The potential role of sensory testing, skin biopsy, and functional brain imaging as biomarkers in chronic pain clinical trials: IMMPACT considerations. J Pain. 2017;18(7):757–77. https://doi.org/10.1016/j.jpain.2017.02.429.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Baron R, Förster M, Binder A. Subgrouping of patients with neuropathic pain according to pain-related sensory abnormalities: a first step to a stratified treatment approach. Lancet Neurol. 2012;11(11):999–1005. https://doi.org/10.1016/S1474-4422(12)70189-8.

    Article  PubMed  Google Scholar 

  27. Blankenburg M, et al. Childhood diabetic neuropathy: functional impairment and non-invasive screening assessment. Diabet Med. 2012;29(11):1425–32. https://doi.org/10.1111/j.1464-5491.2012.03685.x.

    Article  CAS  PubMed  Google Scholar 

  28. Shillo P, et al. Painful and painless diabetic neuropathies: what is the difference? Curr Diab Rep. 2019;19(6):32. https://doi.org/10.1007/s11892-019-1150-5.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Krämer HH, Rolke R, Bickel A, Birklein F. Thermal thresholds predict painfulness of diabetic neuropathies. Diabetes Care. 2004;27(10):2386–91. https://doi.org/10.2337/diacare.27.10.2386.

    Article  PubMed  Google Scholar 

  30. Themistocleous AC, 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. https://doi.org/10.1097/j.pain.0000000000000491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Raputova J, et al. Sensory phenotype and risk factors for painful diabetic neuropathy: a cross-sectional observational study. Pain. 2017;158(12):2340–53. https://doi.org/10.1097/j.pain.0000000000001034.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Baron R, et al. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain. 2017;158(2):261–72. https://doi.org/10.1097/j.pain.0000000000000753.

    Article  PubMed  Google Scholar 

  33. Vollert J, et al. Pathophysiological mechanisms of neuropathic pain: comparison of sensory phenotypes in patients and human surrogate pain models. Pain. 2018;159(6):1090–102. https://doi.org/10.1097/j.pain.0000000000001190.

    Article  PubMed  Google Scholar 

  34. Vollert J, et al. Stratifying patients with peripheral neuropathic pain based on sensory profiles: algorithm and sample size recommendations. Pain. 2017;158(8):1446–55. https://doi.org/10.1097/j.pain.0000000000000935.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Buliteanu A, et al. Validation of a bedside quantitative sensory testing (QST) protocol in chronic neuropathic pain. J Pain. 2018;19(3):S52. https://doi.org/10.1016/j.jpain.2017.12.123.

    Article  Google Scholar 

  36. Zhu GC, et al. Concurrent validity of a low-cost and time-efficient clinical sensory test battery to evaluate somatosensory dysfunction. Eur J Pain. 2019;23(10):1826–38. https://doi.org/10.1002/ejp.1456.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Reimer M, et al. Sensory bedside testing: a simple stratification approach for sensory phenotyping. Pain Rep. 2020;5(3):e820. https://doi.org/10.1097/PR9.0000000000000820.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Demant DT, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. Pain. 2014;155(11):2263–73. https://doi.org/10.1016/j.pain.2014.08.014.

    Article  CAS  PubMed  Google Scholar 

  39. Fields HL, Rowbotham M, Baron R. Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis. 1998;5(4):209–27. https://doi.org/10.1006/nbdi.1998.0204.

    Article  CAS  PubMed  Google Scholar 

  40. Suh Y-G, Oh U. Activation and activators of TRPV1 and their pharmaceutical implication. Curr Pharm Des. 2005;11(21):2687–98. https://doi.org/10.2174/1381612054546789.

    Article  CAS  PubMed  Google Scholar 

  41. Devor M. Sodium channels and mechanisms of neuropathic pain. J Pain. 2006;7(1):3–12. https://doi.org/10.1016/j.jpain.2005.09.006.

    Article  CAS  Google Scholar 

  42. Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. Sodium channels in normal and pathological pain. Annu Rev Neurosci. 2010;33:325–47. https://doi.org/10.1146/annurev-neuro-060909-153234.

    Article  CAS  PubMed  Google Scholar 

  43. Bourinet E, Altier C, Hildebrand ME, Trang T, Salter MW, Zamponi GW. Calcium-permeable ion channels in pain signaling. Physiol Rev. 2014;94(1):81–140. https://doi.org/10.1152/physrev.00023.2013.

    Article  CAS  PubMed  Google Scholar 

  44. Tandon M et al. A simple algorithm to identify likely responders to GRC 17356 in patients of painful diabetic peripheral neuropathy using sensory mapping

    Google Scholar 

  45. de Araujo DSM, Nassini R, Geppetti P, De Logu F. TRPA1 as a therapeutic target for nociceptive pain. Expert Opin Ther Targets. 2020;24(10):997–1008. https://doi.org/10.1080/14728222.2020.1815191.

    Article  CAS  Google Scholar 

  46. Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain. 2012;153(6):1193–8. https://doi.org/10.1016/j.pain.2012.02.021.

    Article  CAS  PubMed  Google Scholar 

  47. Sachau J, Baron R. Neuropathic pain therapy: a puzzle of different approaches to stratify patients. Pain. 2020. https://doi.org/10.1097/j.pain.0000000000002120

  48. Freynhagen R, Baron R, Gockel U, Tölle TR. Pain detect: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006;22(10):1911–20. https://doi.org/10.1185/030079906X132488.

    Article  PubMed  Google Scholar 

  49. Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bouhassira D. Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion? Pain. 2008;138(2):343–53. https://doi.org/10.1016/j.pain.2008.01.006.

    Article  CAS  PubMed  Google Scholar 

  50. Scholz J, et al. A novel tool for the assessment of pain: validation in low back pain. PLoS Med. 2009;6(4):e1000047. https://doi.org/10.1371/journal.pmed.1000047.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Baron R, Tölle TR, Gockel U, Brosz M, Freynhagen R. A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia: differences in demographic data and sensory symptoms. Pain. 2009;146(1):34–40. https://doi.org/10.1016/j.pain.2009.06.001.

    Article  PubMed  Google Scholar 

  52. Bouhassira D, et al. Development and validation of the neuropathic pain symptom inventory. Pain. 2004;108(3):248–57. https://doi.org/10.1016/j.pain.2003.12.024.

    Article  PubMed  Google Scholar 

  53. Spallone V, Greco C. Painful and painless diabetic neuropathy: one disease or two? Curr Diab Rep. 2013;13:7. https://doi.org/10.1007/s11892-013-0387-7.

    Article  CAS  Google Scholar 

  54. Tölle TR, et al. Pain predict: first interim data from the development of a new patient-reported pain questionnaire to predict treatment response using sensory symptom profiles. Curr Med Res Opin. 2019;35(7):1177–85. https://doi.org/10.1080/03007995.2018.1562687.

    Article  PubMed  Google Scholar 

  55. Rice ASC, Finnerup NB, Kemp HI, Currie GL, Baron R. Sensory profiling in animal models of neuropathic pain: a call for back-translation. Pain. 2018;159(5):819–24. https://doi.org/10.1097/j.pain.0000000000001138.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Sveen KA, et al. Small- and large-fiber neuropathy after 40 years of type 1 diabetes: associations with glycemic control and advanced protein glycation: the Oslo Study. Diabetes Care. 2013;36(11):3712–7. https://doi.org/10.2337/dc13-0788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Goyal SN, et al. Challenges and issues with streptozotocin-induced diabetes - a clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chem Biol Interact. 2016;244:49–63. https://doi.org/10.1016/j.cbi.2015.11.032.

    Article  CAS  PubMed  Google Scholar 

  58. Klinck MP, et al. Translational pain assessment: could natural animal models be the missing link? Pain. 2017;158(9):1633–46. https://doi.org/10.1097/j.pain.0000000000000978.

    Article  PubMed  Google Scholar 

  59. Bouhassira D, et al. Stratification of patients based on the neuropathic pain symptom inventory: development and validation of a new algorithm. Pain. 2020. https://doi.org/10.1097/j.pain.0000000000002130

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Acknowledgement

We would like to thank Dilara Kersebaum for her excellent help in language editing.

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Authors and Affiliations

  1. Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Juliane Sachau, Manon Sendel & Ralf Baron

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  1. Juliane Sachau
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  2. Manon Sendel
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  3. Ralf Baron
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Correspondence to Ralf Baron .

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Editors and Affiliations

  1. Royal Hallamshire Hospital, Sheffield Teaching Hospitals and the University of Sheffield Director of Diabetes Research, Sheffield, UK

    Solomon Tesfaye

  2. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Christopher H. Gibbons

  3. Weill Cornell Medicine, Cornell University, Doha, Qatar

    Rayaz Ahmed Malik

  4. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Aristidis Veves

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Sachau, J., Sendel, M., Baron, R. (2023). Sensory Profiles and Diabetic Neuropathy. In: Tesfaye, S., Gibbons, C.H., Malik, R.A., Veves, A. (eds) Diabetic Neuropathy. Contemporary Diabetes. Humana, Cham. https://doi.org/10.1007/978-3-031-15613-7_7

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  • DOI: https://doi.org/10.1007/978-3-031-15613-7_7

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