Mixed Pain: Toward a Consensus Definition and a Mechanism‐Based Framework
Rainer Freynhagen, Bart Morlion, Antonio Alcántara Montero, Daniel Ciampi de Andrade, Andrés Hernández‐Ortiz, Paul W. Hodges, Sasikaan Nimmaanrat, Esther M. Pogatzki‐Zahn, Milton Raff, Roberto D. Rey, Solomon Tesfaye, Andrea Truini, Giustino Varrassi, Ralf BaronABSTRACT
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.