Biology subjects

Andreoli, L.

Publications and source records attributed to Andreoli, L..

3 recordsLinked to original sources

bioRxiv2026

Voluntary wheel running provides pain relief but transiently exacerbates gait impairments in male and female mice with unilateral osteoarthritis

ObjectivePhysical activity is a first-line therapeutic intervention for managing osteoarthritis-related pain and functional impairment. However, the growing literature questions the long-term relevance of exercise-induced improvements in patients, while pre-clinical research evidence base is limited by reliance on stressful, forced exercise paradigms which do not reflect voluntary engagement. Here, we aimed to investigate the effects of voluntary wheel running on the pain experience in mice with joint pain. DesignWe investigated the impact of free access to a running wheel on sensory, functional and affective outcomes following unilateral intra-articular injection of monoiodoacetate in single-housed male and female C57Bl/6J mice. ResultsMonoiodoacetate injection transiently reduced running activity in both sexes; however, females rapidly resumed and sustained high activity levels over a two-month period, while males showed a progressive decline in running distance. Active males and females showed improvements in the monoiodoacetate-induced hindpaw secondary mechanical hypersensitivity. Moreover, mechanical thresholds positively correlated with the distance ran after injury, suggesting a functional relationship between exercise and secondary pain relief. However, access to a wheel temporarily exacerbated several monoiodoacetate-induced gait impairments in both sexes. Finally, while there were no obvious effects of running on anxio-depressive-like behaviours or cognitive functioning, exercise significantly impacted stress-induced faecal output and phenotypic regulation of body weight. ConclusionsOur findings suggest that persistent loading of an injured knee joint may compromise functional outcomes independently of pain relief away from the joint, underscoring a critical consideration for exercise-based therapeutic strategies in osteoarthritis.

animal behavior and cognition↗

bioRxiv2026

Pre-injury subchronic stress confers sex-specific protection against pain-associated symptoms in osteoarthritic mice

Exposure to stress in adulthood alters the manifestation of persistent pain, yet its role in chronic pain vulnerability remains unclear. Here, we report that sub-chronic restraint stress experienced two weeks before unilateral osteoarthritis (OA) induction via intra-articular mono-iodoacetate (MIA) promoted the emergence of a resilient-like phenotype in adult male mice. This was evidenced by decreased MIA-induced mechanical hypersensitivity, improved gait dynamics and lower anxiety-like behaviour. In contrast, stress exposed females exhibited augmented pain-associated symptoms. In males, sub-chronic stress mitigated several MIA-induced molecular changes, including reduced adult hippocampal neurogenesis, increased glucocorticoid receptor levels in the hypothalamic paraventricular nucleus (PVN) and elevated c-Fos expression in deep spinal laminae, periaqueductal gray (PAG) and PVN. RNA sequencing suggested that restraint stress in males primed the spinal cord for an exacerbated GABAergic response post-MIA and pre-empted some pro-nociceptive MIA-induced transcriptional changes. However, the combination of stress and injury disrupted longevity-associated programs and shifted neurons toward a stress-vulnerable state. These findings reveal that prior stress exposure can modulate the long-term pain experience in osteoarthritis, with sexually dimorphic outcomes. Importantly, these results challenge the notion of stress as inherently maladaptive and underscore its potential to foster resilience to chronic pain.

neuroscience↗

bioRxiv2025

Discrete and sequential critical periods organise the development of task-specific sensorimotor circuits in mice

Somatosensory circuits in early life must maintain stable, task-selective pathways while behavioural repertoires undergo rapid change. How such circuits construct these behaviours under evolving functional demands has remained unclear. Here we show that sensorimotor behaviours are shaped through sequential, experience-dependent critical periods rather than a single global window of plasticity. Using transient perturbations of somatosensory input across postnatal development in mice, we identify three discrete life stages that exert lasting effects on adult behaviour. Perturbation during postnatal days 8-12 selectively increases adult sensitivity to dynamic touch. The same manipulation during days 13-17 produces persistent deficits in motor coordination. Perturbation during days 18-22 instead results in lifelong impairments in skilled locomotion. These findings reveal that somatosensory circuits undergo multiple phases of refinement, each aligned with the changing functional needs of the developing organism. This framework of sequential, task-specific critical periods offers a new model for building lifelong sensorimotor function. Significance StatementDeveloping sensory systems must construct precise neural circuits to support dynamic behaviours that change with postnatal experience. We show that somatosensory circuits achieve this through sequential, task-specific critical periods, rather than a single fixed window of plasticity. This dynamic framework demonstrates how experience can guide the stepwise construction of sensorimotor behaviours, offering a new perspective on critical periods across complex, multimodal systems.

neuroscience↗