The role of the brain in the transition from acute to chronic musculoskeletal pain : an investigation of neuroplastic mechanisms and novel treatments

Abstract

Musculoskeletal pain is a leading health problem globally. Its prevalence and associated socioeconomic costs have increased exponentially and this trend is expected to continue in the coming decades. While all stages of musculoskeletal pain contribute to the burden of disease, the costs attributed to chronic pain (pain lasting > 3 months) are most significant. Effective treatment would substantially reduce the impact of chronic musculoskeletal pain at both the individual and societal level. Yet, the effects of current treatments are, at best, moderate for pain and function. One explanation for the limited success of current treatments is an inadequate understanding of the neurophysiological mechanisms that underpin musculoskeletal pain. Addressing the evidence gap surrounding our mechanistic understanding of musculoskeletal pain is essential to guide the development of effective treatments. Maladaptive neuroplasticity, manifesting as altered sensorimotor cortex organisation and impaired central pain processing, is the prevailing theory used to explain the development and maintenance of chronic musculoskeletal pain. Cross sectional evidence derived from individual studies suggests maladaptive neuroplasticity in the primary motor cortex (M1) is present in chronic musculoskeletal pain and is associated with symptoms of pain and movement dysfunction. Yet, a systematic evaluation of the evidence for altered M1 plasticity in chronic pain is absent. Further, no study has characterised neuroplasticity in the acute stage of clinical musculoskeletal pain. This information is critical to better understand the time course of neuroplasticity in musculoskeletal pain. Finally, few treatments exist that specifically target altered neuroplasticity in chronic musculoskeletal pain conditions. Thus, the overarching aim of this thesis was to investigate and target specific mechanisms of neuroplasticity (sensorimotor cortex organisation and central pain processing) in musculoskeletal pain. This aim was achieved through four studies. This thesis provides original and novel insight into our understanding of neuroplasticity in musculoskeletal pain and provides a foundation for the development and testing of novel interventions to reduce pain and disability. Specifically, this thesis demonstrates that: (1) evidence for M1 structural, organisational and functional changes in chronic pain conditions is inconsistent, (2) neuroplasticity in acute LBP is characterised by lower sensorimotor and cingulate cortex excitability and impaired descending inhibitory pain control when compared with pain-free individuals, although inter-individual variability is high and (3) adding tDCS to strengthening exercise may improve pain, function and pain mechanisms in knee osteoarthritis beyond that of exercise applied alone. Notably, subgroups distinguished by high or low S2 and ACC excitability may represent individual adaptation of different cortical strategies that relate to the processing of non-noxious input in acute clinical LBP and could be relevant for pain outcome. However, subgroups determined by a prior history of LBP do not differ in central pain processing in acute LBP. Future studies with larger sample sizes are needed to determine whether altered M1 plasticity is present in chronic musculoskeletal pain and to confirm findings of decreased sensorimotor cortex excitability and altered central pain processing in acute pain. Finally, a fully powered randomised controlled trial is necessary to determine the effectiveness of adding tDCS to strengthening exercise for knee osteoarthritis.

Date of Award	2018
Original language	English