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Peer-reviewedCC BYEuropean Journal of Pain

Mixed Pain: Toward a Consensus Definition and a Mechanism‐Based Framework

  • Rainer Freynhagen1,2
  • Bart J. Morlion3,4
  • Antonio Alcántara Montero5
  • Daniel Ciampi de Andrade6
  • Andrés Hernández-Ortiz7
  • Paul W. Hodges8
  • Sasikaan Nimmaanrat9
  • Esther Miriam Pogatzki-Zahn10
  • Milton Raff11
  • Roberto D. Rey12
  • Solomon Hailemariam Tesfaye13
  • Andrea Truini14
2 more authors
  • Giustino Varrassi15
  • Ralf Baron16
16 affiliations
  1. 1Department of Anaesthesiology Klinikum Rechts der Isar, Technische Universität München Munich Germany
  2. 2Department of Anaesthesiology, Critical Care Medicine & Pain Therapy Benedictus Hospital Feldafing & Tutzing Feldafing Germany
  3. 3Department of Cardiovascular Sciences, Section Anaesthesiology and Algology KU Leuven‐University of Leuven Leuven Belgium
  4. 4The Leuven Centre for Algology and Pain Management University Hospitals Leuven Leuven Belgium
  5. 5Servicio Extremeño de Salud Trujillo Spain
  6. 6Center for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine Aalborg University Aalborg Denmark
  7. 7Pain and Palliative Medicine Instituto Nacional de Ciencias Médicines y Nutrición Salvador Zubirán Mexico City Mexico
  8. 8Centre for Innovation in Pain and Health Research (CIPHeR) The University of Queensland Brisbane Australia
  9. 9Department of Anesthesiology Prince of Songkla University Hat Yai Songkhla Thailand
  10. 10Department of Anaesthesiology, Intensive Care, and Pain Medicine Univerisity Hospital Münster Germany
  11. 11Pain Clinic, Christiaan Barnard Memorial Hospital Cape Town South Africa
  12. 12Instituto Argentino de Investigación Neurológica Universidad de Buenos Aires Buenos Aires Argentina
  13. 13Diabetes Research Unit Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK
  14. 14Department of Human Neuroscience Sapienza University Rome Italy
  15. 15Fondazione Paolo Procacci Rome Italy
  16. 16Division of Neurological Pain Research and Therapy, Department of Neurology Christian‐Albrechts‐Universität Kiel Kiel Germany
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Abstract

BACKGROUND: For decades, clinicians and researchers have struggled to classify pain conditions that do not fit neatly into the nociceptive, neuropathic or nociplastic frameworks. Many common disorders-from chronic low back pain to cancer pain and osteoarthritis-exhibit overlapping mechanisms and have long fallen into the 'grey zone' of mixed pain. This area has intrigued researchers yet frustrated clinicians due to the absence of a clear, unified definition. METHODS: Through an international consensus process led by global leading experts, mixed pain has now been defined as pain that is associated with a lesion, disease or disorder resulting in an overlap of at least two mechanistic pain descriptors (nociceptive, neuropathic or nociplastic). CONCLUSIONS: This new definition may help provide the context needed to align research, refine diagnosis and design mechanism-based therapies for patients with mixed pain. It marks an important step towards conceptual clarification-from confusion to consensus, from overlap to action-transforming mixed pain from an ambiguous concept into a potential framework of modern pain taxonomy. SIGNIFICANCE STATEMENT: This work provides an internationally unified consensus definition of mixed pain, addressing inconsistency in pain terminology and mechanistic classification. By defining mixed pain as the overlap of at least two mechanistic pain descriptors (nociceptive, neuropathic or nociplastic), the framework clarifies conceptual ambiguity while stressing the importance of identifying the underlying pain descriptors, supports a mechanism-based assessment and may facilitate more individualized treatment approaches in complex pain conditions while providing a practical foundation for future research, validation and clinical application.

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Cite

BibTeXRIS
BibTeX
@article{freynhagen2026mixed,
  title = {{Mixed Pain: Toward a Consensus Definition and a Mechanism‐Based Framework}},
  author = {Rainer Freynhagen and Bart J. Morlion and Antonio Alcántara Montero and Daniel Ciampi de Andrade and Andrés Hernández-Ortiz and Paul W. Hodges and Sasikaan Nimmaanrat and Esther Miriam Pogatzki-Zahn and Milton Raff and Roberto D. Rey and Solomon Hailemariam Tesfaye and Andrea Truini and Giustino Varrassi and Ralf Baron},
  journal = {European Journal of Pain},
  year = {2026},
  month = aug,
  doi = {10.1002/ejp.70356},
  url = {https://doi.org/10.1002/ejp.70356},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Mixed Pain: Toward a Consensus Definition and a Mechanism‐Based Framework
AU  - Rainer Freynhagen
AU  - Bart J. Morlion
AU  - Antonio Alcántara Montero
AU  - Daniel Ciampi de Andrade
AU  - Andrés Hernández-Ortiz
AU  - Paul W. Hodges
AU  - Sasikaan Nimmaanrat
AU  - Esther Miriam Pogatzki-Zahn
AU  - Milton Raff
AU  - Roberto D. Rey
AU  - Solomon Hailemariam Tesfaye
AU  - Andrea Truini
AU  - Giustino Varrassi
AU  - Ralf Baron
PY  - 2026
DA  - 2026/08/01
JO  - European Journal of Pain
DO  - 10.1002/ejp.70356
UR  - https://doi.org/10.1002/ejp.70356
AB  - BACKGROUND: For decades, clinicians and researchers have struggled to classify pain conditions that do not fit neatly into the nociceptive, neuropathic or nociplastic frameworks. Many common disorders-from chronic low back pain to cancer pain and osteoarthritis-exhibit overlapping mechanisms and have long fallen into the 'grey zone' of mixed pain. This area has intrigued researchers yet frustrated clinicians due to the absence of a clear, unified definition. METHODS: Through an international consensus process led by global leading experts, mixed pain has now been defined as pain that is associated with a lesion, disease or disorder resulting in an overlap of at least two mechanistic pain descriptors (nociceptive, neuropathic or nociplastic). CONCLUSIONS: This new definition may help provide the context needed to align research, refine diagnosis and design mechanism-based therapies for patients with mixed pain. It marks an important step towards conceptual clarification-from confusion to consensus, from overlap to action-transforming mixed pain from an ambiguous concept into a potential framework of modern pain taxonomy. SIGNIFICANCE STATEMENT: This work provides an internationally unified consensus definition of mixed pain, addressing inconsistency in pain terminology and mechanistic classification. By defining mixed pain as the overlap of at least two mechanistic pain descriptors (nociceptive, neuropathic or nociplastic), the framework clarifies conceptual ambiguity while stressing the importance of identifying the underlying pain descriptors, supports a mechanism-based assessment and may facilitate more individualized treatment approaches in complex pain conditions while providing a practical foundation for future research, validation and clinical application.
SN  - 1090-3801
SN  - 1532-2149
ER  -