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

**Authors:** Emma Pepe, Davide Spinetti, Chiara Ceolin, Roberta Ramonda, Sara Bindoli, Paolo Sfriso, Gabriella Paparella, Michela Sarlo, Giuseppe Sergi, Daniela Mapelli, Marina De Rui, Maria Devita

PMC · DOI: 10.3389/fneur.2026.1734010 · Frontiers in Neurology · 2026-02-09

## TL;DR

This paper suggests the cerebellum may contribute to chronic pain in fibromyalgia by creating persistent prediction errors, leading to disrupted learning and pain chronification.

## Contribution

The paper introduces the novel concept of 'cerebellar fragility' in chronic pain and proposes a new framework for understanding cerebellar involvement in fibromyalgia.

## Key findings

- The cerebellum may generate persistent prediction errors in fibromyalgia, contributing to chronic pain.
- Dysregulation of cerebellar prediction errors could disrupt sensorimotor learning and lead to maladaptive loops.

## 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.

## Linked entities

- **Diseases:** fibromyalgia (MONDO:0005546)

## Full-text entities

- **Genes:** IGKV2D-30 (immunoglobulin kappa variable 2D-30) [NCBI Gene 28881] {aka A1, IGKV2D30}, GPHA2 (glycoprotein hormone subunit alpha 2) [NCBI Gene 170589] {aka A2, GPA2, ZSIG51}
- **Diseases:** anxiety (MESH:D001007), atrophy (MESH:D001284), analgesia (MESH:D000699), rheumatological (MESH:D012216), acute pain (MESH:D059787), fibro-fog (MESH:D009810), cognitive dysfunction (MESH:D003072), cerebellar abnormalities (MESH:D002526), cerebellar hypertrophy (MESH:D006984), FM (MESH:D005356), cerebellar fragility (MESH:D005600), psychiatric (MESH:D001523), cognitive symptoms (MESH:D019954), Pain (MESH:D010146), fatigue (MESH:D005221), sleep disturbances (MESH:D012893), chronic pain (MESH:D059350), depression (MESH:D003866), musculoskeletal pain (MESH:D059352), dysmetria (MESH:D002524), cutaneous, muscular, and visceral pain (MESH:D059265)
- **Chemicals:** Serotonin (MESH:D012701), morphine (MESH:D009020), noradrenaline (MESH:D009638), BioRender (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12927869/full.md

## References

62 references — full list in the complete paper: https://tomesphere.com/paper/PMC12927869/full.md

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Source: https://tomesphere.com/paper/PMC12927869