# Repeated Treadmill Run Preconditioning Induces Prolonged Attenuation of Craniofacial Pain-like Behaviors and Changes in Brain Responses Associated with Persistent Craniofacial Inflammation in Male Mice
> Yusuf A.S.H.

URL kanonis: https://discover.unhas.ac.id/publications/pub_scopus_105045925940
Jurnal / Konferensi: Biomedicines
Tahun terbit: 2026
DOI: https://doi.org/10.3390/biomedicines14071576
ISSN: 22279059
Kuartil SJR: Q1
Citations: 0

## Authors
- Yusuf A.S.H.

## Abstract
Background/Objectives: Regular physical exercise conditioning attenuates nociceptive responses. However, it remains unclear whether physical exercise performed before local inflammation exerts prolonged preventive effects. This study determined whether treadmill run (TR) preconditioning produces sustained preventive effects on craniofacial nociception and associated brain responses following persistent craniofacial inflammation. Methods: Male C57BL/6J mice were assigned to sedentary or TR groups. Daily TR conditioning was performed for 10 days before masseter muscle injection of complete Freund’s adjuvant (CFA) on Day 0. Craniofacial-pain- and related anxiety-like behaviors were determined by the orofacial formalin, elevated plus maze, and open-field tests before and 3 (CFA3) or 7 (CFA7) days after CFA injection. Brain responses in the amygdala, insular cortex, hippocampal CA1, and primary motor cortex were assessed using multiple epigenetic- and neural-activity-related markers. Results: Under sedentary conditions, both CFA3 and CFA7 groups showed increased pain- and anxiety-like behaviors and elevated expression of epigenetic- and neural-activity-related markers in most brain regions. TR preconditioning attenuated these behavioral responses even three and seven days after TR cessation and altered the expression of epigenetic markers in several brain regions, although the direction of change varied by region and time point. TR preconditioning consistently reduced the expression of neural activity markers in most brain areas in both the CFA3 and CFA7 groups, with a few exceptions. Conclusions: TR preconditioning exerted prolonged preventive effects on craniofacial-pain-like behaviors and associated brain responses following craniofacial inflammation.

## Keywords
- Craniofacial
- Medicine
- Hippocampal formation
- Nociception
- Treadmill
- Inflammation
- Masseter muscle
- Anesthesia
- Orofacial pain
- Internal medicine
- Endocrinology
- Neuroplasticity
- Physical exercise
- Central nervous system
- Brain activity and meditation
- Craniofacial abnormality
- Neuroscience
- Tongue
- Prefrontal cortex
- Glucocorticoid
- Habituation
- Hippocampus

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Sumber: Discover Unhas — RIMS Universitas Hasanuddin.
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