Human studies

The clinical activities of PMRI are closely integrated with the clinical research and basic research program. Research developments are quickly translated into the Centre’s multidisciplinary national and international web based educational program which offers a Diploma and Masters degree in Pain Management via the University of Sydney. During 2004 partnerships were negotiated with a major university in the UK and one in the USA, to enhance the Faculty of the educational program and to facilitate international enrolments.

The clinical activitiesof PMRI staff now provide over 40,000 episodes of patient care per annum and in 2002 was recognised by NSWHealth as the flagship centre in this State with the award of Enhancement Funds for clinical programs of $ 571,267 pa for the years 2002,2003 and 2004.

The clinical researchcomponent of PMRI was recognised by the National health and Medical Research Council (NHMRC) as one of only eight centres in all medical research fields in Australia with the award of an NHMRC “Centre of Clinical Excellence in Hospital Based Research” award for the year from 1998-2001. There is now a significant clinical research component of the PMRI’s NHMRC Program Grant in “Dissecting the pain pathways with conotoxins’ which will focus on the development of new systemic and spinal pharmacological options for the treatment of severe pain and developing a ‘fingerprint’ of brain perturbations associated with chronic pain by use of magnetic resonance spectroscopy.

In 2007, there has been a mix of internally initiated and industry sponsored clinical studies. Collaborative projects with the RNSH Spinal Injuries Unit and the Department of Endocrinology also continue.

Clinical Research Projects

• Mechanical Low Back Pain: Diagnosis and Treatment The medial branch of the dorsal ramus of the spinal nerves supplies the spinal facet joints. We are engaged in a randomized prospective placebo controlled study aimed at evaluating the utility of diagnostic medial branch blocks with local anaesthetic and the efficacy of treatment with radiofrequency lesioning. The study will also provide new insights into responses to placebo injections. A target of 100 expected patients will be enrolled by the end of 2008.
• Modified ADAPT Program for treatment of chronic pain in elderly Australians. This randomized prospective controlled trial is evaluating the effectiveness of self management pain strategies in the older age group. The study is the firstof this strategy in this age group and is funded by the Australian Government.
• Development of reproducible assessments of spinal cord injury impairment and function. This study involves the evaluation of new techniques such as transcranial magnetic stimulation, electrical perceptual thresholds and sympathetic skin response. It is hoped that these assessment tools will be helpful in diagnosing and treating the various problems, including pain, that afflict patients with spinal cord injury.
• Treatment of pain associated with osteoarthritis of the knee and low back pain. This is a a Randomized Double-Blind, Placebo- and Active-Control, Parallel-arm, Phase III Study with Controlled Adjustment of Dose to Evaluate the Efficacy and Safety of CG5503 Extended-Release (ER) in Patients with Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee or Low Back Pain. The study drug is a centrally acting analgesic with a dual mode of action being a mu-opioid receptor agonist and an inhibitor of noradrenaline uptake. Sponsored by Janssen Cilag. We have previously established a synergism between an opioid agonist and an alpha2 adrenergic drug clonidine in spinal cord injury pain. Thus the results of this study will be of great interest to our group.
• The treatment of severe neuropathic pain due to Post Herpetic Neuralgia (chronic post-shingles pain). This is A Phase II, Double Blind, Placebo Controlled, Dose-ranging Study in Subjects with postherpetic Neuralgia (PHN) to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Four Doses of TAK-583, Compared with Placebo. Sponsored by Takeda. Tak-583 is an extremely interesting drug that protects neurons from changes in the nervous system that are produced by very severe and prolonged pain. Surprisingly severe pain is associated with excess release of a very small molecule called nitric oxide (NO) which can result in the death of important neurons that “tune down” the pain signal. This is the first of a new class of drugs that attack the “disease process” in the nervous system associated with severe persistent pain.
• Treatment of Severe Cancer  Pain A second exciting new drug has been developed in our Basic Pain Research Program, in collarboration with the University of Queensland. This drug, XEN 2174 is derived from the cone shell fish in Northern Queensland and is a synthetic conopeptide which inhibits the uptake of noradrenaline by a “transporter” which transports noradrenaline across the neuronal synapse. In our basic animal studies, this drug was extremely potent in models of neuropathic pain. Changes in the noradrenaline system are an important part of the “disease process” that is associated with persistent pain. We have recently completed a multi-centre study in patients with severe cancer pain, in which Xen 2174 was administered spinally. The drug proved to be extremely potent for cancer pain and we expect to be able to proceed with more extensive studies in humans in the near future. Sponsored by Xenome.
• Treatment of Type 2 Diabetes  PMRI has a long standing collaboration with the RNSH Department of Endocrinology which aims to develop innovative methodology for the delivery of insulin through the lungs. The same methodology is being used to develop delivery of pain relief drugs through the lungs such as fentanyl and morphine. The current study is “Inhaled Pre-prandial Human Insulin with the AERx® iDMS plus Glimepiride versus Rosiglitazone plus Glimepiride in Type 2 Diabetes: a 26-week, Open-label, Multicentre, Randomised, Parallel Trial to Investigate Safety and Efficacy. Sponsored by NovoNordisk. In the long term, it is hoped that many diabetics will be freed from injections by the ability to deliver insulin via the lungs. It is also hoped that patients after surgery will be able to obtain pain relief with strong morphine like drugs using a hand held device which will deliver morphine directly through the lungs into the blood stream.
• Development of New Treatments for Neuropathic Pain in Spinal Cord Injury PMRI is playing a lead role into the development of improved methodology for the design and execution of randomised, double-blind, placebo-controlled, crossover studies in spinal cord injury patients who suffer from neuropathic pain. The aim of this project is to strengthen current methodologies so that they are able to detect improvement in pain end points in clinical studies. Sponsored by Pfizer.

Group Leader

Prof Michael Cousins

Staff

• Professor Michael Cousins MB BS MD DSc FANZCA FRCA FFPMANZCA FAChPM (RACP)
• A/Prof Michael Nicholas BSc MSc(Hons) MPsychol PhD – Director, Adapt Program
• Dr. Charles Brooker MB BS FANZCA FFPMANZCA – Director, Chronic & Cancer Pain Program
• Ms Linda Critchley MSc B.App.Sc – Co-ordinator of Clinical Research
• Ms Kim Somerville BAppSc(MRS), Ass.Dip.NM, Grad.Cert. Diabetes Management – Research Co-ordinator
• Ms Emily Patterson EEN – Research Nurse

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