Neuroplasticity and Pain: Examining the Influence of Exercise on the Sensory Nervous System
Creators: Villarreal Andrade, Dania N
Publisher: name: University of Alberta Library
Year: 2024

<p>Chronic pain is associated with many diseases and is one of the biggest contributors to decreased quality of life in many people worldwide. Neuropathologies arise from long lasting damage to the nervous system leading to hypersensitivity in sensory neurons. While some forms of plasticity like molecular sensitization and hyperactivity in nociceptors are well understood to be associated with pain pathologies, our knowledge on how structural changes in neurons contribute to pain phenomena is limited. Studies on neuronal regeneration after injury often focus on functional motor recovery but do not address how neurotrophic factors and nerve outgrowth relate to long-lasting pain. In this study, we focused on characterizing the structural status of primary sensory neurons associated with enhanced pain sensitivity. We used a hyperalgesic priming model in mice to study how acute pain transitions intro chronic pain, since we can produce prolonged pain sensitivity in the absence of persistent inflammation. To assess how structural plasticity might contribute to prolonged pain in this model, we used primary dorsal root ganglia (DRG) cultures to assess changes in neuronal outgrowth and cell morphology. Because pain pathologies affect females disproportionately, we also sought to investigate sex differences. We found that challenging a mouse with 50pg tumour necrosis factor α produced sustained hypersensitivity in female mice with a subsequent injection of 100ng prostaglandin E2. The priming stimulus dose was too little to produce the same priming effect in males. In females, DRG outgrowth analysis revealed increased outgrowth per cell, increased number of neurites and greater branching density – we referred to this type of outgrowth as ‘arbourous’. Due to limited research on the effects of exercise on pain fibre modulation, we sought to investigate how exercise might modulate hyperalgesic priming related pain. Research on the benefits of exercise often focus of physical rehabilitation and do not always address the sensory system. Because exercise is ofteniiirecommended to everyone as a healthy treatment, we sought to characterize how exercise influences phenotypic plasticity and its relationship to pain. In female mice, our results demonstrate that two weeks of voluntary wheel-running exercise alone promotes increased neurite outgrowth in DRG neuron cultures. Conversely, males show a decrease in outgrowth, which hint at potential differences in the benefits of aerobic exercise between males and females. Due to these differences, we proceeded to investigate how wheel-running might influence neuronal outgrowth in the context of hyperalgesic priming in female mice. Our results suggest that two weeks of wheel-running does not ameliorate pain sensitivity in female mice and does not alter neuronal outgrowth arbour. Remarkably, four weeks of running was sufficient to reduce pain sensitivity in primed female mice. Assessment of neuronal outgrowth reveals decreased branching density and smaller neurite arbour in primed female mice after four weeks of running treatment. Immunostaining for brain-derived neurotrophic factor (BDNF) and cFos hint at proteins that may be related to changes in sensory neuronal structure and increased neuronal activity. Future research will investigate how modifications to structural plasticity in vivo may be related to changes in nociceptor activity and prolonged pain.</p>