Exploring the hypothetical role of cerebellar pain prediction errors in fibromyalgia-associated chronic pain

Despite growing evidence that the cerebellum contributes to sensory, motor, cognitive, and affective domains, its role in chronic pain remains poorly understood. Fibromyalgia (FM), a rheumatological condition in which chronic pain is a hallmark feature, offers a paradigmatic model. Although neuroimaging studies have reported increased cerebellar activity in response to nociceptive stimuli, its contribution to pain chronification has been largely overlooked. This perspective paper proposes that the cerebellum may play a central role in FM by generating persistent prediction errors. Dysregulation of this mechanism may result in a mismatch between sensorimotor inputs and expected outcomes, for both noxious and innocuous stimuli, progressively disrupting error-based learning. We term this hypothesized state 'cerebellar fragility', where the system becomes locked into maladaptive loops. Reconceptualizing cerebellar involvement in chronic pain opens new perspectives for research and therapeutic strategies.

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Publication Details

Journal
Frontiers in Neurology
Published
2026-02-09
DOI
https://doi.org/10.3389/fneur.2026.1734010
Primary Topic
Fibromyalgia and Chronic Fatigue Syndrome Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Exploring the hypothetical role of cerebellar pain prediction errors in fibromyalgia-associated chronic pain

Daniela Mapelli, R. Ramonda, Michela Sarlo, Marina De Rui et al.
Frontiers in Neurology
Fibromyalgia and Chronic Fatigue Syndrome Research
article

Exploring the hypothetical role of cerebellar pain prediction errors in fibromyalgia-associated chronic pain

Daniela Mapelli, R. Ramonda, Michela Sarlo, Marina De Rui, Gabriella Paparella, Davide Spinetti, Chiara Ceolin, Sara Bindoli, Giuseppe Sergi, Emma Pepe, Paolo Sfriso, Maria Devita
article en

Abstract

Despite growing evidence that the cerebellum contributes to sensory, motor, cognitive, and affective domains, its role in chronic pain remains poorly understood. Fibromyalgia (FM), a rheumatological condition in which chronic pain is a hallmark feature, offers a paradigmatic model. Although neuroimaging studies have reported increased cerebellar activity in response to nociceptive stimuli, its contribution to pain chronification has been largely overlooked. This perspective paper proposes that the cerebellum may play a central role in FM by generating persistent prediction errors. Dysregulation of this mechanism may result in a mismatch between sensorimotor inputs and expected outcomes, for both noxious and innocuous stimuli, progressively disrupting error-based learning. We term this hypothesized state 'cerebellar fragility', where the system becomes locked into maladaptive loops. Reconceptualizing cerebellar involvement in chronic pain opens new perspectives for research and therapeutic strategies.

Frontiers in NeurologyVol. 17
University of Padua (IT), University of Urbino (IT), IRCCS Eugenio Medea (IT)
European Commission, Ministero della Salute, Università degli Studi di Padova
Openalex Percentile: Top 64%
Fibromyalgia and Chronic Fatigue Syndrome Research
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Exploring the hypothetical role of cerebellar pain prediction errors in fibromyalgia-associated chronic pain — Daniela Mapelli, R. Ramonda, et al. · Frontiers in Neurology (2026) | TGRS Research Map | TGRS