1. 2025;28;483-494Is Fibromyalgia a Nociplastic or a Mixed-pain Condition? International, Multidisciplinary Recommendations for Pain Phenotyping in Fibromyalgia Syndrome
   Narrative Review
   Ismail Saracoglu, PhD, Randy Neblett, PhD, Esra Akin, PhD, Bilge Basakci Calik, MD, C. Paul van Wilgen, PhD, Marc Schiltz, PhD, Josue Fernandez Carnero, MD, Bart Morlion, PhD, Pawel Zalewski, MD, Slawomir Kujawski, PhD, Aleksandra Modlinska, PhD, Rainer Freynhagen, ., Robert Gerwin, MD, Mariana Arias Avila, MD, Paula Rezende Camargo, MD, and Jo Nijs, PhD.

BACKGROUND: Fibromyalgia syndrome (FMS) is a complex condition characterized by numerous symptoms, especially long-lasting widespread pain. Available evidence suggests that the main causes of FMS are nociplastic pain mechanisms, but nociceptive and neuropathic pain components can also be involved, which would in these cases characterize FMS as a mixed-pain condition. In 2021, a comprehensive set of clinical criteria and grading systems was developed in accordance with the International Association for the Study of Pain. The establishment of these criteria is an important step toward precision pain medicine, with great potential for the assessment and treatment of FMS.

OBJECTIVES: The aim of this study was to develop clinical recommendations for pain phenotyping, including the phenotyping of mixed pain, in patients with FMS.

STUDY DESIGN: Narrative review.

METHODS: Within this framework, an international and multidisciplinary group of pain specialists have developed clinical recommendations for integrating a mixed pain phenotype into the current framework of phenotyping FMS. A modified nominal group technique was used to develop the consensus recommendations. A manual is provided to allow clinicians to differentiate between predominant nociplastic pain and mixed pain when phenotyping FMS patients. 

RESULTS: A 7-step diagnostic approach, performed in 2 parts, is presented and illustrated using 3 case examples to enhance understanding and encourage effective implementation of this approach in research settings and clinical practice. 

LIMITATIONS: Studies examining the clinometric properties of these recommendations and this grading system for mixed pain in FMS are warranted. 

CONCLUSION: The current recommendations systematically summarize the methods that allow individuals with FMS to be classified into nociplastic or mixed pain phenotypes, based on potential nociceptive and neuropathic pain components.

KEY WORDS: Fibromyalgia syndrome, mixed pain, neuropathic pain, nociceptive pain, nociplastic pain, precision medicine