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Central neuropathic pain

Nature Reviews Disease Primers volume 9, Article number: 73 (2023) Cite this article

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Abstract

Central neuropathic pain arises from a lesion or disease of the central somatosensory nervous system such as brain injury, spinal cord injury, stroke, multiple sclerosis or related neuroinflammatory conditions. The incidence of central neuropathic pain differs based on its underlying cause. Individuals with spinal cord injury are at the highest risk; however, central post-stroke pain is the most prevalent form of central neuropathic pain worldwide. The mechanisms that underlie central neuropathic pain are not fully understood, but the pathophysiology likely involves intricate interactions and maladaptive plasticity within spinal circuits and brain circuits associated with nociception and antinociception coupled with neuronal hyperexcitability. Modulation of neuronal activity, neuron–glia and neuro-immune interactions and targeting pain-related alterations in brain connectivity, represent potential therapeutic approaches. Current evidence-based pharmacological treatments include antidepressants and gabapentinoids as first-line options. Non-pharmacological pain management options include self-management strategies, exercise and neuromodulation. A comprehensive pain history and clinical examination form the foundation of central neuropathic pain classification, identification of potential risk factors and stratification of patients for clinical trials. Advanced neurophysiological and neuroimaging techniques hold promise to improve the understanding of mechanisms that underlie central neuropathic pain and as predictive biomarkers of treatment outcome.

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Fig. 1: Distribution of sensory abnormalities and central neuropathic pain.
Fig. 2: From sensory-discriminative mechanisms to the clinical pain phenotype.
Fig. 3: Molecular mechanisms in spinal and supraspinal neuronal circuitry.
Fig. 4: The thermal grill illusion — a model for central neuropathic pain?
Fig. 5: Grading system for central neuropathic pain.
Fig. 6: Neuromodulatory techniques for central neuropathic pain.
Fig. 7: Progression and monitoring of central neuropathic pain.

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Acknowledgements

J.R. is supported by a postdoctoral fellowship from the International Foundation for Research in Paraplegia (IRP, no. P191F) and the Clinical Research Priority Program (CRPP) “Pain” of the University of Zurich. D.C.A. is working at the Center for Neuroplasticity and Pain (CNAP), which is supported by the Danish National Research Foundation (DNRF121). D.C.A. is supported by a Novo Nordisk grant NNF21OC0072828 and ERC Horizon Europe Consolidator grant PersoNINpain 101087925. K.D.D. is the Canada Research Chair in Acute and Chronic Pain Research and is supported by funds from the Canadian Institutes of Health Research and the Mayday Fund. S.M.G. acknowledges support from the Rebecca L. Cooper Medical Research Foundation. R.P.S. is supported by NS 107364. N.B.F.’s research is supported by the Lundbeck Foundation R359-2020-2620.

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  1. Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Jan Rosner & Nanna B. Finnerup

  2. Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland

    Jan Rosner

  3. Department of Neurology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland

    Jan Rosner

  4. Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark

    Daniel C. de Andrade

  5. Division of Brain, Imaging and Behaviour, Krembil Brain Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada

    Karen D. Davis

  6. Department of Surgery and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Karen D. Davis

  7. Centre for Pain IMPACT, Neuroscience Research Australia, Sydney, New South Wales, Australia

    Sylvia M. Gustin

  8. NeuroRecovery Research Hub, School of Psychology, University of New South Wales, Sydney, New South Wales, Australia

    Sylvia M. Gustin

  9. International Collaboration on Repair Discoveries, ICORD, University of British Columbia, Vancouver, Canada

    John L. K. Kramer

  10. Department of Anaesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada

    John L. K. Kramer

  11. Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Rebecca P. Seal

  12. Departments of Neurobiology and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Rebecca P. Seal

  13. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark

    Nanna B. Finnerup

Authors
  1. Jan Rosner
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  2. Daniel C. de Andrade
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  3. Karen D. Davis
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  4. Sylvia M. Gustin
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  5. John L. K. Kramer
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  6. Rebecca P. Seal
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  7. Nanna B. Finnerup
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Contributions

Introduction (J.R. and N.B.F.); Epidemiology (J.L.K.K.); Mechanisms/pathophysiology (J.R., R.P.S. and K.D.D.); Diagnosis, screening and prevention (D.C.A., J.L.K.K. and J.R.); Management (N.B.F., D.C.A. and S.M.G.); Quality of life (S.M.G.); Outlook (J.R. and N.B.F.) and Overview of the Primer (J.R. and N.B.F.). All authors contributed to and critically reviewed all sections.

Corresponding author

Correspondence to Nanna B. Finnerup.

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Competing interests

J.R. and J.L.K.K. receive consultancy fees from AXONIS Therapeutics. N.B.F. has received consultancy fees from Vertex, Novartis Pharma, NeuroPN, Nanobiotix, Neurvati and Samiona and has undertaken consultancy work for Aarhus University with remunerated work for Biogen, Merz and Confo Therapeutics. She has received grants from IMI2PainCare an EU IMI 2 (Innovative Medicines Initiative) public–private consortium and the companies involved include Grunenthal, Bayer, Eli Lilly, Esteve and Teva, outside the submitted work. The other authors declare no competing interests.

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Nature Reviews Disease Primers thanks Nadine Attal, David Bennett and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Rosner, J., de Andrade, D.C., Davis, K.D. et al. Central neuropathic pain. Nat Rev Dis Primers 9, 73 (2023). https://doi.org/10.1038/s41572-023-00484-9

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