Pain

MEMOIR is an Australian government-funded clinical trial for Complex Regional Pain Syndrome (CRPS). MEMOIR is testing two new interventions for people with CRPS – a new drug and rehabilitation program. MEMOIR will be conducted remotely, via Telehealth, allowing for Australia-wide recruitment of eligible participants.

Please click on the link below to check if you are eligible.

What is Complex Regional Pain Syndrome (CRPS)?

CRPS is a disabling pain disorder. It affects approximately 5,000 people in Australia annually. CRPS is characterised by severe burning, stinging and stabbing pain. People with CRPS may not be able to use their affected limb and their ability to work or participate in normal social activities can be severely restricted. Currently, there are no interventions for CRPS whose efficacy is supported by high-quality evidence.

What is the MEMOIR Trial?

The MEMOIR trial is an Australian Government-funded, randomised controlled trial testing two novel treatments for CRPS. MEMOIR will test whether two new interventions, produce greater improvements in pain intensity and pain interference than placebo and standard care for CRPS.

The MEMOIR trial will be delivered remotely, via Telehealth, allowing Australia-wide recruitment of 160 participants. MEMOIR is the first, large, high-quality clinical trial to evaluate of the effects of two new interventions.

What is usual care?

Usual care is the continuation of your current management for CRPS, excluding the therapies outlined in the exclusion criteria. This might include medical, physical or psychological management of CRPS.

Will these treatments improve my CRPS?

The effectiveness of these treatments is not known. We are attempting to find this out by conducting this research study. MEMOIR is the first, large, high-quality clinical trial to evaluate of the effects of two new interventions.

Who can participate in the MEMOIR Trial?

To be eligible for the MEMOIR trial, you must:

• Have (or suspected to have) chronic CRPS of 6 months to 5 years duration
• Have at least moderate pain intensity and disability as measured by validated scales
• Be 18 years of age or over
• Have access to a computer (or tablet) and internet
• Have CRPS in a single limb only

You will not be eligible to participate in the MEMOIR trial if:

• You are female, of child-bearing potential and not using reliable contraceptive method(s)
• You are pregnant and lactating
• You have an allergy to the study drug family (NMDA antagonists)
• You are taking high dose opioid analgesics or methadone
• You are taking high dose anticonvulsant medicines
• You are taking certain types of antidepressant medicines
• You are taking anti-psychotic medicines
• You have high blood pressure, or your blood pressure is managed with medicine
• You have a heart-rhythm disorder, or you are taking a medicine to manage this condition
• You have a kidney condition
• You have a history of neurological conditions (stroke, seizure, Alzheimer’s)
• You have an implanted spinal cord or nerve stimulator
• You are currently using Graded Motor Imagery

What is required as a participant of the MEMOIR Trial?

Participation in this trial requires a large time commitment for participants. The time commitment varies depending on the group that you are allocated to.

All study participants will be asked to take an oral drug or placebo for 16 weeks and maintain daily records, and complete outcome questionnaires, four times throughout the study (these will take approximately 30 minutes to complete).

Participants receiving rehabiliation will be asked to attend 7, 60-minute physiotherapy sessions via Zoom and will complete online modules incorporating rehabilitative activities and education, for approximately 30-60 minutes each day, for 16 weeks.

Participants receiving usual care will be asked to continue their current treatment, excluding any treatments that are listed in the study exclusion criteria.

The trial treatment period will run for a period of 16 weeks. After this, we will require you to complete two further assessments at 6 months and 12 months.

Will I get paid to be a participant in the MEMOIR Trial?

Participation in this study will not cost you anything, nor will you be paid.

How can I contact the MEMOIR Trial?

0414 062 189

memoir@unsw.edu.au

MEMOIR Team

MEMOIR consolidates the expertise of the following international scientists and clinicians:

• Prof James McAuley, School of Health Sciences & NeuRA, University of New South Wales
• A/Prof Sylvia Gustin, School of Psychology & NeuRA, University of New South Wales
• Prof Andrew McLachlan, Dean of Pharmacy, University of Sydney
• Prof Lorimer Moseley, University of South Australia
• Prof Benedict Wand, School of Physiotherapy, University of Notre Dame Australia
• Dr Neil O’Connell, Brunel University London
• Dr Hopin Lee, University of Oxford
• Prof Eric Visser, School of Medicine, University of Notre Dame Australia
• Prof Sallie Lamb, University of Exeter
• Mr Michael Ferraro, NeuRA, University of New South Wales
• Dr Aidan Cashin, NeuRA, University of New South Wales
• Dr Saurab Sharma, NeuRA, University of New South Wales

Keep up to date with the MEMOIR Trial and the latest chronic pain research:

The MEMOIR trial has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, protocol number: X20-0325.

The MEMOIR Trial is supported by:

• NeuRA
• University of New South Wales
• NHRMC
• University of South Australia
• University of Sydney
• University of Notre Dame

Researchers: A/Prof Sylvia Gustin, Dr Negin Hesam-Shariati, Dr Wei-Ju Chang, A/Prof James McAuley, Dr Andrew Booth, A/Prof Toby Newton-John, Prof Chin-Teng Lin, A/Prof Zina Trost

Chronic pain is a global health problem, affecting around one in five individuals in the general population. The understanding of the key role of functional brain alterations in the generation of chronic pain has led researchers to focus on pain treatments that target brain activity. Electroencephalographic (EEG) neurofeedback attempts to modulate the power of maladaptive EEG frequency powers to decrease chronic pain. Although several studies provide promising evidence, the effect of EEG neurofeedback on chronic pain is uncertain. This systematic review aims to synthesise the evidence from randomised controlled trials (RCTs) to evaluate the analgesic effect of EEG neurofeedback.

The search strategy will be performed on five electronic databases (Cochrane Central, MEDLINE, Embase, PsycInfo, and CINAHL) for published studies and on clinical trial registries for completed unpublished studies. We will include studies that used EEG neurofeedback as an intervention for people with chronic pain. Risk of bias tools will be used to assess methodological quality of the included studies. RCTs will be included if they have compared EEG neurofeedback with any other intervention or placebo control. The data from RCTs will be aggregated to perform a meta-analysis for quantitative synthesis. In addition, non-randomised studies will be included for a narrative synthesis. The data from non-randomised studies will be extracted and summarised in a descriptive table. The primary outcome measure is pain intensity assessed by self-report scales. Secondary outcome measures include depressive symptoms, anxiety symptoms, and sleep quality measured by self-reported questionnaires. Further, we will investigate the non-randomised studies for additional outcomes addressing safety, feasibility, and resting-state EEG analysis.

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.

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

Researchers: Associate Professor Sylvia Gustin, Nell-Norman-Nott, Dr Negin Hesam- Shariati, Dr. Chelsey Wilks (University of Washington).

Emerging evidence has shown that negative emotional states play a key role in the development and maintenance of chronic pain. The No Worries Trial will evaluate the effectiveness of a four-week internet-delivered Dialectical Behaviour Therapy (DBT) skills training to help chronic pain sufferers cope with painful, fearful, worrisome, anxious, and negative thoughts and emotions. Moreover, by having the DBT skills training online it is more accessible to those in remote communities, to those with restricted mobility, and more broadly it adds to the knowledge of internet-delivered therapies at a time when online is increasingly necessary to deliver treatment due to COVID-19.

Chronic neuropathic pain (NP) can be a debilitating secondary condition for persons with spinal cord injury (SCI) and effective pharmacological and non-pharmacological treatments remain elusive. This project brings together international experts in basic science and clinical approaches to SCI NP for a rigorous multisite randomized clinical trial to examine the efficacy and mechanisms of an advanced interactive virtual reality (VR) walking intervention (VRWalk).

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.

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.

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

Social media is a potentially powerful tool to provide a message of education and reassurance to the general public about low back pain. This project will use social media to educate the general public about low back pain and promote self-management.

The project involves three stages. Firstly, we will conduct a content analysis to gain an insight into social media users’ perceptions and understanding about low back pain. This could determine whether social media could serve as an educational tool through which accurate information related to low back pain could be disseminated to the public.

Second, a recent Delphi survey of 150 low back pain researchers identified 30 key messages considered to be important for the general public to know about LBP. These statements provide evidence-based information on the diagnosis, prognosis and management of LBP and are intended to educate, reassure and promote self-management. We will investigate the attitude of the general public towards these messages.

Third, working in conjunction with a media company Y&R, we will design and test a social media campaign to encourage self-management for people with low back pain.

For people with back pain who are having trouble with their sleep. We are testing whether a simple sleep tablet will help people reduce their pain and sleep better.

For people with long term back pain that is not getting better. We are testing two pain treatment programs that target the brain, for people with chronic low back pain.

For people with a new low back pain episode. We are testing early intervention to reduce the risk of developing chronic low back pain.

Chronic pain, defined as pain lasting for >3 months, typically develops from injuries to deep tissues such as muscle, yet little is known about how long-lasting pain affects a person’s blood pressure or capacity to control their muscles. This project assesses the effects of tonic muscle pain on sympathetic nerve activity and stretch sensitivity of muscle spindles.