Recalibrating Pain–Mood Coupling in Fibromyalgia: A Hypothesis-Generating Multisystem Neurobehavioral Framework for Mindfulness-Based Interventions

Background/Objectives: Fibromyalgia (FM) is a nociplastic pain syndrome characterized by chronic widespread pain, fatigue, sleep disturbance, cognitive dysfunction, and heightened sensitivity to somatic and environmental stimuli. Depressive symptoms and major depressive disorder (MDD) frequently co-occur with FM and are associated with greater disability, pain catastrophizing, sleep disruption, and poorer treatment response. Although pharmacological treatments can reduce symptoms in some patients, many individuals experience persistent functional and affective burden, highlighting the need for mechanism-based adjunctive strategies. Mindfulness-based interventions (MBIs), particularly mindfulness-based stress reduction (MBSR), have shown promise for improving functional impact, pain catastrophizing, perceived stress, depressive symptoms, sleep-related burden, and quality of life in FM. However, the effects of MBIs on pain intensity and biomarkers are less consistent. Methods: This narrative mechanistic review develops a hypothesis-generating multisystem neurobehavioral framework to explain how MBIs may influence pain–mood coupling in FM with depressive symptom burden. We define pain–mood recalibration as a reduction in the extent to which pain intensity, bodily vigilance, and interoceptive threat appraisal automatically drive depressive symptoms, rumination, avoidance, and functional disengagement. Results: Fibromyalgia-specific evidence most strongly supports cognitive–emotional mechanisms, including reduced catastrophizing, psychological inflexibility, rumination, perceived stress, and avoidance. Interoceptive, neural-network, autonomic, immune-inflammatory, and sleep-fatigue-behavioral pathways remain exploratory and require prospective mediation and moderation testing. Conclusions: Future trials should prioritize active controls, ecological momentary assessment, longitudinal biomarkers, neuroimaging, interoceptive tasks, and formal mediation/moderation models to determine which patients benefit, through which mechanisms, and under what biological and psychological conditions.