Dr Siobhan Schabrun

Brain and Knee Muscle Weakness Study

Why Does Quadriceps Weakness Persist after Total Knee Replacement?

An Exploration of Neurophysiological Mechanisms

Total knee replacement is a commonly performed surgery for treating end-staged knee osteoarthritis. Although most people recover well after surgery, weakness of the quadriceps muscles (the front thigh muscles) persists long after the surgery (at least for 12 months), despite intensive physiotherapy and exercise. Quadriceps muscle weakness is known to be associated with more severe pain and greatly affect daily activities.

This study aims to investigate the mechanisms underlying weakness of the quadriceps muscles in people with knee osteoarthritis and total knee replacement. We hope to better understand the relationship between the changes of the brain and a loss of quadriceps muscle strength after total knee replacement.

The study might be a good fit for you if you:

• Scheduled to undergo a total knee replacement;
• The surgery is scheduled within the next 4 weeks;
  • Do not have a previous knee joint replacement in the same knee;
  • Do not have high tibial osteotomy;
  • Do not have neurological disorders, epilepsy, psychiatric conditions, other chronic pain conditions;
  • Do not have metal implants in the skull;
  • Do not have a loss of sensation in the limbs.

If you decide to take part you would:

• Be contacted by the researcher to determine your eligibility for the study
• Be scheduled for testing if you are eligible and willing to take part in the study
• Sign the Consent Form when you attend the first testing session
• Attend 3 testing sessions (approximately 2 hours per session): 1) before total knee replacement, 2) 3 months and 3) 6 months after total knee replacement. The testing will include several non-invasive measures of brain representations of the quadriceps muscles, central pain mechanisms, and motor function and questionnaires.

Will I be paid to take part in the research study?

You will be reimbursed ($50.00 per session) for travel and parking expenses associated with the research study visits.

If you would like more information or are interested in being part of the study, please contact:

Name: Dr Wei-Ju Chang

Email: w.chang@neura.edu.au

Phone: 02 9399 1260

This research is being funded by the Physiotherapy Research Foundation.

BOOST – Repetitive transcranial magnetic simulation to bolster analgesic effects of quadriceps str

Osteoarthritis affects more than 20% of Australians aged over 60. The knee joint is commonly affected, causing persistent pain and difficulty in daily activities. Although exercise is the cornerstone of conservative treatment for knee osteoarthritis and recommended in all international guidelines, its effects are, at best, moderate.

BOOST is a ‘proof of concept’ study to explore the use of a novel intervention combining non-invasive brain stimulation and exercise therapy in people with knee osteoarthritis. This intervention applies repetitive transcranial magnetic stimulation, a safe and painless non-invasive brain stimulation, targeting specifically the brain region involved in pain processing and motor function to enhance the effects of exercise therapy.

The study might be a good fit for you if you:

• Are aged ≥ 50 years with knee osteoarthritis.
• Have knee pain for more than 3 months and on most days of the past month.
• Have average pain intensity higher than 4 out 10 in the past week.
• Do not have previous knee joint replacement or high tibial osteotomy.
• Do not knee surgery or joint injection in past 6 months.
• Do not have planned surgery in the next 9 months.
• Do not use oral corticosteroids currently or in the past 4 weeks.
• Do not have systemic arthritis, previous knee fracture or malignancy.
• Do not have other condition affecting lower limb function.
• Do not participate in knee strengthening exercise in past 6 months.
• Do not have a loss of sensation of the affected leg.
• Do not have neurological or psychiatric disorders.
• Do not have contraindications to brain stimulation such as epilepsy, metal implant in the skull.
• Do not use neuroactive drugs.

If you are eligible and agree to participate, you will be asked to attend 2 sessions per week for 6 weeks (each session includes 15 minutes of active or sham brain stimulation plus 30 minutes one-to-one exercise by a physiotherapist); 2 testing sessions (about 1.5 hours per session) before the start and after the completion of the intervention. All sessions will take place in a laboratory at NeuRA.

If you would like more information or are interested in being part of the study, please contact:

Name: Dr Wei-Ju Chang

Email: w.chang@neura.edu.au

Phone: 02 9399 1260

This research is being funded by the ANZMUSC Clinical Trial Network.

MODULATE: Altering the brains sensitivity to pain

Pain is the single most common reason for seeking medical attention. Under normal circumstances, pain acts to signal injury and is a protective response that prevents further damage and promotes tissue healing. People differ not only in their ability to detect and tolerate pain, but also in their ability to recover from an injury, with some people experiencing pain that outlasts the duration of tissue healing. Interventions to treat or cure chronic pain have had limited success.

Recent research has identified a novel cortical biomarker that could identify individuals at risk of developing chronic pain, which could be used to identify individuals at high risk of transitioning from acute to chronic pain (PREDICT project). However, whether a causal relationship exists between this cortical biomarker and pain is unknown.

The pain biomarker is based on rhythmic patterns of electrical activity in the brain and is measured using electroencephalography (EEG). Previous research suggests that the speed of this rhythmic activity can be altered through the administration of nicotine. MODULATE will attempt to alter the speed of the brain’s rhythmic activity, using nicotine gum, and observe the impact on pain. The project will help determine whether a causal relationship exists between the biomarker and pain.

PREDICT: A novel cortical biomarker signature for predicting pain sensitivity

Temporomandibular disorder (TMD) is the second most common musculoskeletal pain condition and is associated with pain and tenderness of the jaw. Although a number of biological factors have shown an association with chronic TMD in cross-sectional and case control studies, there are currently no biomarkers that can predict the development of chronic symptoms. Because of the difficulty in treating chronic pain, development of brain signal predictive biomarkers is of growing interest.

The PREDICT project will aim to develop a predictive biomarker signature of pain severity and duration using two commonly available techniques – electroencephalogram (EEG) and transcranial magnetic stimulation (TMS) – and perform initial clinical validation in first onset TMD. The biomarker could have utility in identifying patients at high risk of transitioning from acute to chronic pain and has additional potential for clinical application in the treatment and prevention of chronic pain.

This project will be carried out in collaboration with a team at the University of Maryland, Baltimore lead by A/Prof David Seminowicz (see more information here).

PREDICT Publications

Seminowicz DA, Bilska K, Chowdhury NS, Skippen P, Millard SK, Chiang A, Chen S, Furman AJ, & Schabrun SM. (2020). A novel cortical biomarker signature for predicting pain sensitivity: protocol for the PREDICT longitudinal analytical validation study. Pain Reports, 5(4), e833. doi: 10.1097/PR9.0000000000000833

TRANSLATE: Improving the translation of research evidence into practice

Effective, safe and cost-efficient healthcare is achieved when treatment is evidence based. Yet, it takes 17 years on average for research evidence to be translated into clinical care. This results in the overuse of ineffective treatments – those that do more harm than good – and the underuse of effective treatments – those that can improve symptoms and promote faster recovery after illness of injury. As a result, there is a huge gap between the healthcare people should receive and the care they do receive. TRANSLATE seeks to reduce the evidence-clinical care gap by implementing and monitoring evidence-based models of care in private practice.

BRAIN-Boost: Non-invasive brain stimulation combined with exercise for knee OA

Osteoarthritis is a major global health problem with no cure. Exercise is the cornerstone of conservative treatment, but effects on pain and physical function are at best, moderate. Non-invasive brain stimulation has the potential to bolster the effects of exercise therapy, resulting in greater improvements in pain and function than can be achieved with exercise alone. Here we will investigate this possibility in a randomized controlled trial of people living with knee osteoarthritis.

DISCOVER: Discovery of a cortical biomarker signature for pain

Low back pain (LBP) is ranked as the top single cause of disability worldwide. Costs have risen faster than for any other health condition and LBP is now equal to ischemic heart disease, and second only to cancer, as the costliest health condition. Approximately 40% of people who experience acute LBP develop chronic pain. These individuals are unresponsive to treatment, experience high levels of pain, struggle to perform daily tasks and frequently develop psychosocial comorbidities. The enormous scale of the problem is matched only by the mystery that accompanies it: despite decades of research, why some people develop chronic LBP while others do not, remains unknown.

The identification of biomarkers that can predict who will develop chronic LBP is a holy grail of pain research. Our new research has uncovered evidence for a unique biomarker signature that appears to predict i) an individual’s susceptibility to high pain severity, even before pain begins and ii) an individual’s susceptibility to developing chronic LBP following an acute episode. These biomarkers are now undergoing detailed investigation in on-going studies.

UNmaPPed: Understanding the physiology of persistent pain

People in pain move differently. Yet, the biological basis for altered movement in pain is poorly understood. This lack of understanding has led to treatments for persistent pain that target generic symptoms with limited effect. This NHMRC-funded trial is the first to examine how different aspects of the nervous system are altered in pain and how this relates to movement. This information will guide the development of new treatment strategies for persistent pain in future.

UPWaRD: Understanding persistent pain where it resides – in the brain.

Persistent musculoskeletal pain is one of the most significant health issues in the developed world. Termed a ‘Western epidemic’, low back pain is the most common form of persistent musculoskeletal pain and a leading cause of suffering and disability. Despite the enormity of the problem, many current therapies target generic symptoms, not underlying mechanisms, with limited effect. In 2010, the Australian National Pain Summit concluded ‘the management of pain is shockingly inadequate’. This assessment is not surprising given that critical information on the biological changes that underpin persistent low back pain is lacking. The UPWaRD study is a 5-year NHMRC-funded trial that investigates the role of brain plasticity, along with biological changes in the spinal cord, hormonal changes, genetics and stress, in the development of persistent low back pain.

https://www.upwardbackpainstudy.com