Pain Management Human Studies
Head of laboratory
On this page:
Overview of research program
We conduct 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. Human Studies projects include:
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 first of 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) that 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 collaboration 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. Thedrug 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 that 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.
Selected publications
Siddall PJ, McClelland JM, Rutkowski SP, Cousins MJ. (2003) A longitudinal study of the prevalence and characteristics of pain in the first five years following spinal cord injury. Pain 103:249-257
Blyth FM, March LM, Nicholas MK, Cousins MJ (2003) Chronic pain, work performance and litigation. Pain 103:41-47
Cousins MJ. History of the development of pain management with spinal opioid and non-opioid drugs. (2003) In Meldrum ML(ed) “Opioids and Pain relief: a historical perspective, Progress in Pain Research and Management”. IASP Press Seattle 25: 141-155
Siddall PJ, Cousins MJ. (2004) Persistent pain as a disease entity: implications for clinical management. Anesthesia & Analgesia 99: 510-20
Blyth FM, March LM, Nicholas MN, Cousins MJ. (2005) Self-management of chronic pain: a population based study. Pain 11:285-292
Murphy PM, Cousins MJ. (2005) Neural blockade and neuromodulation in persistent pain management. In: Merskey H, Loeser JD, Dubner R (Eds). The Paths of Pain 1975-2005. IASP Press Seattle
Finniss DG, Murphy PM, Brooker C, Nicholas MK, Cousins MJ. (2006) Complex regional pain syndrome in children and adolescents. European Journal of Pain 10:767-770
Van Leeuwin MT, Blyth FM, March LM, Nicholas MK, Cousins MJ. (2006) Chronic pain and reduced work effectiveness: the hidden cost to Australian Employers. European Journal of Pain 10:161-66
Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK (2006) Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Neurology 67:1792-1800
Siddall PJ, Stanwell P, Woodhouse A, Somorjai RL, Dolenko B, Nikulin A, Bourne L, Himmelreich V, Leon C, Cousins MJ, Mountford, CE (2006) Magnetic resonance spectroscopy detects biochemical changes in the brain associated with chronic low back pain: a preliminary report. Anesthesia & Analgesia 102:1164-8
