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      Neuropathic pain in children: Steps towards improved recognition and management

      review-article
      a , b , *
      EBioMedicine
      Elsevier
      Neuropathic pain, Children, Adolescents, Quantitative sensory testing, Neuropathy, Chronic pain

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          Abstract

          Neuropathic pain in children can be severe and persistent, difficult to recognise and manage, and associated with significant pain-related disability. Recognition based on clinical history and sensory descriptors is challenging in young children, and screening tools require further validation at older ages. Confirmatory tests can identify the disease or lesion of the somatosensory nervous system resulting in neuropathic pain, but feasibility and interpretation may be influenced by age- and sex-dependent changes throughout development. Quantitative sensory testing identifies specific mechanism-related sensory profiles; brain imaging is a potential biomarker of alterations in central processing and modulation of both sensory and affective components of pain; and genetic analysis can reveal known and new causes of neuropathic pain. Alongside existing patient- and parent-reported outcome measures, somatosensory system research methodologies and validation of mechanism-based standardised end-points may inform individualised therapy and stratification for clinical trials that will improve evidence-based management of neuropathic pain in children.

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          Most cited references75

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          Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

          New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis.
            • Record: found
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            • Article: found

            Neuropathic pain

            Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.
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              Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

              The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                25 November 2020
                December 2020
                25 November 2020
                : 62
                : 103124
                Affiliations
                [a ]Developmental Neurosciences Program, UCL Great Ormond St Institute of Child Health, London, United Kingdom
                [b ]Department of Anaesthesia and Pain Medicine, Great Ormond St Hospital NHS Foundation Trust, London, United Kingdom
                Author notes
                [* ]Correspondence address: UCL Great Ormond Street Institute of Child Health, Clinical Neurosciences (Pain Research), 4th Floor PUW South, 30 Guilford St., London WC1N 1EH, United Kingdom. suellen.walker@ 123456ucl.ac.uk
                Article
                S2352-3964(20)30500-4 103124
                10.1016/j.ebiom.2020.103124
                7704400
                33248373
                4fd6292d-bbe0-4206-bfd1-e1618ad6a65f
                © 2020 The Author

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 September 2020
                : 21 October 2020
                : 28 October 2020
                Categories
                Review

                neuropathic pain,children,adolescents,quantitative sensory testing,neuropathy,chronic pain

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