An exploration of homeostatic plasticity in musculoskeletal pain

Abstract

The brain has a remarkable capacity to reorganise itself through life. When changes occur at a cellular level between neurons, this is known as synaptic plasticity. Synaptic plasticity has been proposed to be a key mechanism underpinning the learning and memory formation that occurs following afferent input (i.e., incoming stimuli from movement and sensation). However, synaptic plasticity in the human brain follows a positive loop cycle where incoming stimuli can lead to excessive synaptic strengthening (long-term potentiation; LTP) or weakening (long-term depression; LTD). To prevent overexpression of LTP or LTD, regulatory mechanisms termed 'homeostatic plasticity' promote stability during synaptic plasticity. A large body of evidence suggests that short- or long-term changes to synaptic plasticity takes place following afferent input. Similarly, evidence also suggests synaptic plasticity is altered in individuals experiencing incoming stimuli that are painful. However, no study has examined homeostatic plasticity during pain. Published studies that have examined homeostatic plasticity in individuals with pathology have been conducted in neurological conditions such as writer's cramp, and chronic migraine. These studies provide preliminary evidence that impaired homeostatic plasticity is associated with altered synaptic plasticity with patients displaying abnormally high primary motor cortex (M1) excitability, altered cortical organisation, increased pain perception, and sensorimotor dysfunction. As altered synaptic plasticity and similar clinical features have been observed in individuals with chronic musculoskeletal pain, it is possible that homeostatic plasticity is impaired during pain. Thus, the broad goal of this thesis was to explore the effect of pain, using a clinical chronic musculoskeletal pain population and an experimental pain model, on homeostatic plasticity in the M1. To address this broad goal, three primary research studies were conducted.

Date of Award	2018
Original language	English