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Understanding how pain is processed in the brain


The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage”. Acute pain is the pain that says you’ve been hurt. It is often temporary and begins suddenly, often as a result of injury or inflammation. Sensory inputs from damaged tissue project via specific nerve fibres (nociceptors) to the brain, which generates a perception of pain – the quality of which depends on the tissue of origin. Reflex responses to a painful stimulus serve to protect the body from further damage: superficial pain – that originating in the skin – leads to withdrawal of the body part from the stimulus, whereas deep pain – that originating in muscle, for example – leads to protective responses that limit further damage to the injured body part.

Pain might be mild and last just a moment, or it might be severe and last for weeks or months. As the body repairs the damage the nociceptive messages cease, encouraging use of the injured or inflamed body part once again. It is important to get moving again as over-protection of an injury or under-use of a limb may lead to further complications.

Things that will help pain to feel better include making changes to exercise, where appropriate – so if running has caused an injury, switch to cycling or swimming; treat the injury with therapy, such as physical therapy, occupational therapy or massage therapy; or try meditation or deep relaxation techniques that aim to relax each part of your body or help manage pain.

In most cases, pain does not last longer than three months, and it disappears when the underlying cause of pain has been treated or has healed. Unrelieved pain, however, might lead to chronic pain. Chronic pain is considered to be pain that lasts for three months past the point of injury, and it is now generally accepted that changes in the brain are responsible for maintaining the pain long after the nociceptive signals of tissue damage have stopped.


The No Worries Trial

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.

MEMOIR – a clinical trial for Complex Regional Pain Syndrome

Complex Regional Pain Syndrome (CRPS) is a serious health condition, affecting approximately 20,000 people in Australia. It is characterised by severe burning, stinging and stabbing pain. People with CRPS are unable to use their painful limb and their ability to work or participate in normal social activities is severely restricted. Currently, there are no effective treatments for CRPS.

A vast body of research has demonstrated changes in brain processes in CRPS. The MEMOIR trial will investigate the effectiveness of two novel brain-directed treatments to reduce pain and improve function in people with CRPS.

MEMOIR consolidates the expertise of scientists and clinicians from NeuRA (A/Prof James McAuley, A/Prof Sylvia Gustin, Mr Michael Ferraro), the University of South Australia (Prof Lorimer Moseley), the University of Sydney (Prof Andrew McLachlan), the University of Notre Dame Australia Fremantle (Prof Benedict Wand, Prof Eric Visser), the University of Exeter (Prof Sallie Lamb), Brunel University London (Dr Neil O’Connell) and the University of Oxford (Dr Hopin Lee).

Due to the COVID-19 global pandemic, the commencement of MEMOIR has been delayed. Recruitment for MEMOIR will commence in September 2020.

If you are interested in being contacted about our CRPS research, please leave your details below and we will be in touch once recruitment begins. 

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A Multi-Site Randomized Clinical Trial to Examine the Efficacy and Mechanisms of Immersive Virtual W

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).

DISCOVER-pain: 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.



Medicines for Back Pain

Medicines are the most common treatment for back pain. The aim of this program of research is to improve our understanding of the clinical effects of medicines.

Studies currently in progress:

  1. Scoping review of paracetamol, NSAIDs and opioid analgesics for chronic low back pain (led by Matthew K Bagg). The objective of this study is to identify and describe the characteristics of available clinical trials of commonly used analgesic medicines for chronic low back pain. This information will inform the design and conduct of other studies in the research program.
  2. Paracetamol, NSAIDs and opioid analgesics for chronic low back pain: a network meta-analysis (led by Matthew K Bagg). The objective of this study is to produce information about the clinical effects of available analgesic medicines for chronic low back pain. This information will be available in a Cochrane review to assist clinical prescription of medicines. The protocol is published and available here.
  3. Prescribing practices of medicines for adults with low back pain: a systematic review (led by Michael Wewege). The objective of this study is to determine how different medicines are prescribed to adults with low back pain and how this differs across countries. The protocol for this study is being developed.
  4. Analgesic medicines for adults with low back pain: a network meta-analysis (led by Michael Wewege). The objective of this study is to evaluate the comparative effectiveness of a range of analgesic medicines for adults across different classifications of low back pain. The protocol for this study has been submitted for publication.
  5. Muscle relaxant medicines for low back pain: a systematic review and meta-analysis (led by Aidan Cashin and Thiago Folly). The objective of this study is to determine the effectiveness and tolerability of muscle relaxant medicines for adults with low back pain. The protocol is available here.
  6. Novel biologic medicines for low back pain: a systematic review and meta-analysis (led by Rodrigo Rizzo). The objective of this study is to determine the effectiveness and tolerability of novel biologic medicines for adults with low back pain. The protocol is available here.

Completed studies:

  1. Evaluation of the impact of unpublished data from clinical trial registries on the effects of medicines for low back pain (led by Matthew Bagg). The objective of this study was to evaluate whether there is a difference between clinical trial data that are published and those that are not published. The findings are published in the Journal of Clinical Epidemiology.
  2. Antidepressant medicines for low back pain: a systematic review and meta-analysis (led by Michael Ferraro). The objective of this study was to determine the effectiveness and tolerability of antidepressant medicines for adults with low back pain. The findings have been submitted for publication. The protocol is available here.

Medicines for Back Pain – Publications:

  • Bagg MK, McLachlan AJ, Maher CG, Kamper SJ, Williams CM, Henschke N, Wand BM, Moseley GL, Hübscher M, O’Connell NE, van Tulder MW, Nikolakopoulou A, McAuley JH. (2018). Paracetamol, NSAIDS and opioid analgesics for chronic low back pain: a network meta-analysis [Protocol]. Cochrane Database of Systematic Reviews, Issue 6. doi: 10.1002/14651858.CD013045. PMCID: PMC6513465
  • Bagg MK, O’Hagan E, Zahara P, Wand BM, Hübscher M, Moseley GL, McAuley JH. (2020). Reviews may overestimate the effectiveness of medicines for back pain: systematic review and meta-analysis. Journal of Clinical Epidemiology. doi: 10.1016/ j.jclinepi.2019.12.006. PMID: 31816418

Medicines for Back Pain – Registrations of Study Protocols:

  • Folly T, Bagg MK, Wewege M, Ferraro MC, Schabrun S, Gustin SM, Day R, McAuley JH. (2019) UMbRELLA: Understanding efficacy and safety of Muscle RELaxant medicines for Low back pain – systematic Literature review and meta-Analysis (protocol).Open Science Framework, available at: https://osf.io/xuw5h
  • Rizzo RN, Bagg MK, Ferraro MC, Wewege M, Cashin A, Leake HB, O’Hagan E, Jones M, McAuley JH. (2020). Efficacy and safety of medicines targeting neurotrophic factors in the management of low back pain: protocol for a systematic review and meta-analysis. Open Science Framework, available at: https://osf.io/zax6d
  • Ferraro MC, Bagg MK, McAuley JH. (2019). RADICAL: Systematic Review of Anti-Depressant Medicines if Considered Analgesics for Low Back Pain (protocol). Open Science Framework, available at: https://osf.io/cedm3

Social Media for Low Back Pain

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.

RESOLVE Trial for Chronic Low Back Pain

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.

The effects of tonic muscle pain on the sympathetic and somatic motor systems

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.

What else is happening in Pain research at NeuRA?