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Maximizing treatment efficacy through patient stratification in neuropathic pain trials

Nature Reviews Neurology volume 19, pages 53–64 (2023)Cite this article

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Abstract

Treatment of neuropathic pain remains inadequate despite the elucidation of multiple pathophysiological mechanisms and the development of promising therapeutic compounds. The lack of success in translating knowledge into clinical practice has discouraged pharmaceutical companies from investing in pain medicine; however, new patient stratification approaches could help bridge the translation gap and develop individualized therapeutic approaches. As we highlight in this article, subgrouping of patients according to sensory profiles and other baseline characteristics could aid the prediction of treatment success. Furthermore, novel outcome measures have been developed for patients with neuropathic pain. The extent to which sensory profiles and outcome measures can be employed in routine clinical practice and clinical trials and across distinct neuropathic pain aetiologies is yet to be determined. Improvements in animal models, drawing on our knowledge of human pain, and robust public–private partnerships will be needed to pave the way to innovative and effective pain medicine in the future.

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Fig. 1: Stratification approaches along the drug development pipeline.
Fig. 2: Subgrouping of patients with painful peripheral neuropathy.

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Change history

  • 12 December 2022

    In the version of this article initially published, the incorrect journal (J. Pain) was listed for ref. 134, which has now been corrected (Pain Rep.) in the HTML and PDF versions of the article.

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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

    Ralf Baron

  2. Neuroscience, Physiology and Pharmacology, University College London, London, UK

    Anthony H. Dickenson

  3. Physiology Department, Pontificia Universidad Católica de Chile, Santiago, Chile

    Margarita Calvo

  4. Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile

    Margarita Calvo

  5. Department of Neurology, Yale University School of Medicine, New Haven, CT, USA

    Sulayman D. Dib-Hajj

  6. Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK

    David L. Bennett

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  1. Ralf Baron
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  2. Anthony H. Dickenson
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  3. Margarita Calvo
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  4. Sulayman D. Dib-Hajj
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  5. David L. Bennett
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Contributions

The authors contributed equally to all aspects of the article.

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Correspondence to Ralf Baron.

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Competing interests

R.B. has received R.B. has received research funding from EU Projects Europain (115007), DOLORisk (633491), IMI Paincare (777500), the German Federal Ministry of Education and Research (BMBF): Verbundprojekt: Frühdetektion von Schmerzchronifizierung (NoChro) (13GW0338C), German Research Network on Neuropathic Pain (01EM0903), Pfizer, Grünenthal, Mundi Pharma, Alnylam, Zambon, Bayer, Sanofi Aventis. He has been a speaker for Pfizer, Sanofi Aventis, Grünenthal, Mundipharma, Lilly, Desitin, Teva, Bayer, MSD, Seqirus, Novartis, TAD, Eva, Takeda, Ology, Ever, Amicus, Novo Nordisk, Chiesi, Stada, Hexal, Viatris. He has acted as a consultant for Pfizer, Sanofi Aventis, Grünenthal, Lilly, Novartis, Bristol-Myers Squibb, Biogenidec, AstraZeneca, Daiichi Sankyo, Glenmark, Seqirus, Teva, Genentech, Mundipharma, Galapagos, Kyowa Kirin, Vertex, Biotest, Celgene, Desitin, Regeneron, Theranexus, Abbott, Bayer, Akcea, Asahi Kasei, AbbVie, Air Liquide, Alnylam, Lateral, Hexal, Angelini, Janssen, SIMR, Confo, Merz, Neumentum, Hoffmann-La Roche, AlgoTherapeutix, Nanobiotix, AmacaThera. M.C. is a councillor at the International Society for the Study of Pain (IASP), a board member of the Neuropathic Pain Special Interest Group of IASP and a board member of the Neuropathic Pain Consortium (SIG of Peripheral Nerve Society). D.L.B. has acted as a consultant on behalf of Oxford Innovation for Amgen, Bristows, LatigoBio, GSK, Ionis, Lilly, Olipass, Orion, Regeneron and Theranexus over the past 2 years. He has received research funding from Lilly and AstraZeneca. He is an inventor for patent application ‘A method for the treatment or prevention of pain or excessive neuronal activity or epilepsy’ (application no. US16/337,428). He is a member of the Medical Reseach Council Neuroscience and Mental Health Board for which he receives reimbursement. He is an executive member of the Neuropathic Pain Special Interest Group of IASP. S.D.D.-H. has consulted with Ionis and Alnylam Pharmaceuticals over the past 2 years and is a board member of the Neuropathic Pain Special Interest Group of IASP. A.H.D. declares no competing interests.

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Nature Reviews Neurology thanks L. Asan, who co-reviewed with U. Bingel; M. Schmelz; I. Gilron; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

IMI-Europain: https://www.imi.europa.eu/projects-results/project-factsheets/europain

Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT): http://www.immpact.org

Innovative Medicines Initiative (IMI)-PainCare Consortium: https://www.imi-paincare.eu

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Baron, R., Dickenson, A.H., Calvo, M. et al. Maximizing treatment efficacy through patient stratification in neuropathic pain trials. Nat Rev Neurol 19, 53–64 (2023). https://doi.org/10.1038/s41582-022-00741-7

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