BIOMARKERS ENABLING PRECISION NEURO-MUSCULOSKELETAL HEALTH REHABILITATION (BIOSPHERE) – CHANGING THE PARADIGM
T. Rebbeck1, J. Elliott2, S. Schabrun3, D. Walton3
All authors, affiliations and abstracts have been published as submitted.
1University of Sydney, Faculty of Medicine and Health, Sydney, Australia, 2The University of Sydney & Northern Sydney Local Health District, The Kolling Institute, St Leonards, Australia, 3University of Western Ontario, Faculty of Health Science/ School of Physical Therapy, London, Canada
Learning objective 1: Participants will improve knowledge and understanding of
1. Novel brain neurobiological mechanisms that may contribute to neuro-musculoskeletal (N-MSK) pain and recovery.
1. Novel brain neurobiological mechanisms that may contribute to neuro-musculoskeletal (N-MSK) pain and recovery.
Learning objective 2: Participants will improve knowledge and understanding of
2. How peripheral biomarkers (eg blood and hair cortisol) interact with psychological and social variables and recovery after N-MSK pain conditions.
2. How peripheral biomarkers (eg blood and hair cortisol) interact with psychological and social variables and recovery after N-MSK pain conditions.
Learning objective 3: Participants will improve knowledge and understanding of
3. How this new knowledge may be used to develop novel treatments and be integrated into precision models of care that are truly person centred.
3. How this new knowledge may be used to develop novel treatments and be integrated into precision models of care that are truly person centred.
Description: Background to the problem: Neuro-musculoskeletal (N-MSK) pain and trauma is a global burden, contributing to > 107m million disability – adjusted life years (DALY’s; 2015 Global Burden of Disease study). Over 50% of people experiencing common N-MSK pain and traumatic conditions such as low back pain, whiplash or knee pain have ongoing pain and disability. Currently, known risk factors for ongoing pain are largely psychosocial in nature, leaving a gap on known biological mechanisms that may contribute and could potentially be targeted in treatments. In this Focussed Symposium, our global leading presenters will discuss new biological mechanisms that may underpin N-MSK pain and trauma. We will discuss how these may be integrated into a truly BIO-psychosocial approach to care and “crystal ball gaze” on how we see future models of care could be personalised to a precision rehabilitation model that ultimately solves this global burden.
Professor Jim Elliott will open this Symposium. He will discuss how in the majority of cases of non-catastrophic trauma (involving the head/neck), structural damage on conventional imaging applications is rarely associated with symptoms. However, recent longitudinal studies (using advanced neuroimaging techniques) across three separate cultures, have observed and quantified early expression of muscle degeneration in tandem with brain network modulation, loss of myelin in spinal cord white matter pathways and other known risk factors (e.g. high initial pain and signs of post-traumatic stress). These observations were most evident in those with poor functional recovery, providing a prognostic link between psychological and measurable biological processes. Prof Elliott’s presentation will focus on the clinical assessment of the patient at ‘high risk’ of non-recovery, and how routine imaging protocols may not be necessary (or at least need to be reconsidered) in the vast majority of patients following injury.
Second, Prof Siobhan Schabrun will discuss her lab's recent work using human pain models of the transition to prolonged pain and clinical pain populations. This work has identified novel cortical biomarkers (detected using- Trans Magnetic Stimulation (TMS) and EEG) that may predict who will develop chronic pain. This presentation will discuss data linking an individual’s cortical activity to their experience of pain severity and recovery and will highlight findings from the UPWaRD prospective cohort study of individuals with acute low back pain showing that cortical activity in the acute stage of pain may be a cause of persistent symptoms at 6-months. Consideration will be given to interventions that could modulate cortical activity and improve clinical outcomes.
Third, A/Prof David Walton will discuss how the interaction between peripheral biomarkers (blood, hair cortisol) interact with psychological and social variables to explain and predict experiences of acute post-traumatic pain and subsequent 12-month recovery. Using findings from biopsychosocial SYMBIOME longitudinal data banking project, Dr Walton will encourage participants to consider the influences of prior life stress, trauma, and health-related pre-existing traits of the injured individual and how those can be used to improve interpretation and understandings of post-trauma pain and rehabilitation decisions.
Fourth, A/Prof Rebbeck will discuss new knowledge on the difference between brain biomarkers (neurochemicals) in N-MSK pain, trauma and headache conditions compared with controls. She will present information on how these biomarkers (GABA+ and glutamate) are related to clinical change in pain status, and the potential for brain neurochemicals as indicators of treatment response. She will discuss her lab's work on the development and validation of risk assessment tools in N-MSK pain and trauma settings. She will then outline how this new information could be integrated into existing risk- stratified models of care.
Finally, a facilitated audience discussion will focus on how this new knowledge could direct future clinical care pathways for N-MSK conditions.
Implications/conclusions: A range of neurobiological mechanisms are being identified in N-MSK conditions including brain (cortical, neurochemical, functional connectivity) and peripheral (blood, cortisol, muscle degeneration) biomarkers. These biomarkers are associated with higher levels of pain severity and non-recovery and have potential as novel targets for treatment. Early identification of these biomarkers with targeted intervention can potentially prevent the transition to chronicity. We propose that future treatment for people with MSK conditions therefore could be revolutionised by targeting these BIO mechanisms additional to the current PSYCHOSOCIAL approach. Further, given no one encounters pain and trauma in a vacuum, integration of the life experience and social context is critical to changing pain trajectories. Such an approach will move the current paradigm from the status quo to precision / bespoke rehabilitation, and has the potential to significantly reduce the burden of MSK conditions, one that has not shifted for decades.
Professor Jim Elliott will open this Symposium. He will discuss how in the majority of cases of non-catastrophic trauma (involving the head/neck), structural damage on conventional imaging applications is rarely associated with symptoms. However, recent longitudinal studies (using advanced neuroimaging techniques) across three separate cultures, have observed and quantified early expression of muscle degeneration in tandem with brain network modulation, loss of myelin in spinal cord white matter pathways and other known risk factors (e.g. high initial pain and signs of post-traumatic stress). These observations were most evident in those with poor functional recovery, providing a prognostic link between psychological and measurable biological processes. Prof Elliott’s presentation will focus on the clinical assessment of the patient at ‘high risk’ of non-recovery, and how routine imaging protocols may not be necessary (or at least need to be reconsidered) in the vast majority of patients following injury.
Second, Prof Siobhan Schabrun will discuss her lab's recent work using human pain models of the transition to prolonged pain and clinical pain populations. This work has identified novel cortical biomarkers (detected using- Trans Magnetic Stimulation (TMS) and EEG) that may predict who will develop chronic pain. This presentation will discuss data linking an individual’s cortical activity to their experience of pain severity and recovery and will highlight findings from the UPWaRD prospective cohort study of individuals with acute low back pain showing that cortical activity in the acute stage of pain may be a cause of persistent symptoms at 6-months. Consideration will be given to interventions that could modulate cortical activity and improve clinical outcomes.
Third, A/Prof David Walton will discuss how the interaction between peripheral biomarkers (blood, hair cortisol) interact with psychological and social variables to explain and predict experiences of acute post-traumatic pain and subsequent 12-month recovery. Using findings from biopsychosocial SYMBIOME longitudinal data banking project, Dr Walton will encourage participants to consider the influences of prior life stress, trauma, and health-related pre-existing traits of the injured individual and how those can be used to improve interpretation and understandings of post-trauma pain and rehabilitation decisions.
Fourth, A/Prof Rebbeck will discuss new knowledge on the difference between brain biomarkers (neurochemicals) in N-MSK pain, trauma and headache conditions compared with controls. She will present information on how these biomarkers (GABA+ and glutamate) are related to clinical change in pain status, and the potential for brain neurochemicals as indicators of treatment response. She will discuss her lab's work on the development and validation of risk assessment tools in N-MSK pain and trauma settings. She will then outline how this new information could be integrated into existing risk- stratified models of care.
Finally, a facilitated audience discussion will focus on how this new knowledge could direct future clinical care pathways for N-MSK conditions.
Implications/conclusions: A range of neurobiological mechanisms are being identified in N-MSK conditions including brain (cortical, neurochemical, functional connectivity) and peripheral (blood, cortisol, muscle degeneration) biomarkers. These biomarkers are associated with higher levels of pain severity and non-recovery and have potential as novel targets for treatment. Early identification of these biomarkers with targeted intervention can potentially prevent the transition to chronicity. We propose that future treatment for people with MSK conditions therefore could be revolutionised by targeting these BIO mechanisms additional to the current PSYCHOSOCIAL approach. Further, given no one encounters pain and trauma in a vacuum, integration of the life experience and social context is critical to changing pain trajectories. Such an approach will move the current paradigm from the status quo to precision / bespoke rehabilitation, and has the potential to significantly reduce the burden of MSK conditions, one that has not shifted for decades.
References:
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- Hoggarth MA, Elliott JMet al. Recovery from Whiplash Influenced by Macromolecular Changes in Spinal Cord White Matter? Sci Rep 10, 22221 2020.
- Higgins J, Elliott JM,et al.Network Disruption in Whiplash. Am J Neuroradiol. 2020, Jun;41(6):994-1000.
- Jenkins LC.... Schabrun SM.Somatosensory Cortex Excitability in the Acute Stage of Low Back Pain Causes Chronic Pain. J Pain. 2022 Feb;23(2):289-304.
- Cavaleri R.... Schabrun SM. Repetitive transcranial magnetic stimulation of the primary motor cortex expedites recovery in the transition from acute to sustained experimental pain: a randomised, controlled study. Pain. 2019 Nov;160:2624-2633.
Funding acknowledgements: Trudy Rebbeck is supported by a National Health and Medical Research Council Career Development Fellowship.
All authors, affiliations and abstracts have been published as submitted.
