Neuropathic pain

Abstract

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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Figure 1: The peripheral and central changes induced by nerve injury or peripheral neuropathy.
Figure 2: Neuroanatomical distribution of pain symptoms and sensory signs in neuropathic pain conditions.
Figure 3: Schematic representation of the conditioned pain modulation.
Figure 4: Diagnosing neuropathic pain.
Figure 5: Subgrouping patients with peripheral neuropathic pain based on sensory signs.
Figure 6: Example interventional treatments for neuropathic pain.

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Acknowledgements

L.C. acknowledges support from the UMB and the National Institute of Dental and Craniofacial Research (NIDCR) at the US NIH (R01DE025946). A.H.D. and D.L.B. acknowledge support from the Wellcome Trust Pain Consortium. R.B. acknowledges support from the European Union Project No. 633491: DOLORisk, IMI Europain, the German Federal Ministry of Education and Research (ERA_NET NEU-RON/IM-PAIN Project) and the German Research Network on Neuropathic Pain, NoPain system biology and the German Research Foundation. R.B. also acknowledges support from the German Federal Ministry of Education and Research (BMBF), the ERA_NET NEURON/IM-PAIN Project (01EW1503), the German Research Network on Neuropathic Pain (01EM0903), NoPain system biology (0316177C) and the German Research Foundation (DFG). D.Y. acknowledges support from the Israel Science Foundation, European Horizons 2020 and the US Department of Defense. S.N.R. acknowledges support from the NIH (NS26363).

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Introduction (L.C. and T.L.); Epidemiology (D.B.); Mechanisms/pathophysiology (A.H.D., L.C., D.Y. and R.F.); Diagnosis, screening and prevention (R.B., A.T. and R.H.D.); Management (N.A., N.B.F., S.N.R. and C.E.); Quality of life (E.K.); Outlook (R.H.D. and D.L.B.); Overview of the Primer (L.C.).

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Correspondence to Luana Colloca.

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Competing interests

L.C. has received lecture honoraria (Georgetown University and Stanford University) and has acted as speaker or consultant for Grünenthal and Emmi Solution. R.B. is an industry member of AstraZeneca, Pfizer, Esteve, UCB Pharma, Sanofi Aventis, Grünenthal, Eli Lilly and Boehringer Ingelheim; has received lecture honoraria from Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic Inc. Neuromodulation, Eisai, Lilly, Boehringer Ingelheim, Astellas, Desitin, Teva Pharma, Bayer-Schering, MSD and Seqirus; and has served as a consultant for Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic Inc. Neuromodulation, Eisai, Lilly, Boehringer Ingelheim Pharma, Astellas, Desitin, Teva Pharma, Bayer-Schering, MSD, Novartis, Bristol-Myers Squibb, Biogen idec, AstraZeneca, Merck, AbbVie, Daiichi Sankyo, Glenmark Pharmaceuticals, Seqirus, Genentech, Galapagos NV and Kyowa Hakko Kirin. A.H.D. has acted as speaker or consultant forSeqirus, Grünenthal, Allergan and Mundipharma. D.B. has acted as a consultant for Grünenthal, Pfizer and Indivior. D.L.B. has acted as a consultant for Abide, Eli Lilly, Mundipharma, Pfizer and Teva. D.Y. received a lecture honorarium from Pfizer and holds equity in BrainsGate and Theranica. R.F. has acted as an advisory board member for Abide, Astellas, Biogen, Glenmark, Hydra, Novartis and Pfizer. A.T. has received research funding, lecture honoraria and acted as speaker or consultant for Mundipharma, Pfizer, Grünenthal and Angelini Pharma. N.A. has received honoraria for participation in advisory boards or speaker bureau by Astellas, Teva, Mundipharma, Johnson and Johnson, Novartis and Sanofi Pasteur MSD. N.B.F. has received honoraria for participation in advisory boards from Teva Pharmaceuticals, Novartis and Grünenthal, and research support from EUROPAIN Investigational Medicines Initiative (IMI). E.K. has served on the advisory boards of Orion Pharma and Grünenthal, and received lecture honoraria from Orion Pharma and AstraZeneca. R.H.D. has received research grants and contracts from the US FDA and the US NIH, and compensation for activities involving clinical trial research methods from Abide, Aptinyx, Astellas, Boston Scientific, Centrexion, Dong-A, Eli Lilly, Glenmark, Hope, Hydra, Immune, Novartis, NsGene, Olatec, Phosphagenics, Quark, Reckitt Benckiser, Relmada, Semnur, Syntrix, Teva, Trevena and Vertex. S.N.R. has received a research grant from Medtronic Inc. and honoraria for participation in advisory boards of Allergan, Daiichi Sankyo, Grünenthal USA Inc. and Lexicon Pharmaceuticals. C.E. and T.L. declare no competing interests.

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Colloca, L., Ludman, T., Bouhassira, D. et al. Neuropathic pain. Nat Rev Dis Primers 3, 17002 (2017). https://doi.org/10.1038/nrdp.2017.2

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