Michael G. DeGroote Institute for Pain Research and Carefhs.mcmaster.ca/paininstitute/documents/Open...

of 52

Michael G. DeGroote Institute for Pain Research and

Care

Open House

INFORMATION BOOKLET

6 November, 2008

Geraldo’s at LaSalle Park, Burlington

of 52

Illness is the doctor to whom we pay most heed: To kindness, to knowledge we make promises; only pain we obey

Proust

of 52

Table of Contents

The Michael G. DeGroote Institute for Pain Research and Care 4

A Tribute to Mr. DeGroote 5

National Pain Awareness Week 6

Open House Poster 7

Vision 8

Mission 9

Environmental Scan 10

Leadership 11

Osteoarthritis Pain Research 13

Peripheral Neuropathic Pain Research 16

Central Post-stroke Pain Research 20

Rheumatoid Arthritis Pain Research 23

Bone Cancer Pain Research 25

Low Back Pain Research 29

Iconic Pain Assessment Tool 32

Technical Support for the Research Group 35

Community Alliances for Health Research and Knowledge Translation in Pain 37

Funding Sources 42

Community Outreach – Health Care Professionals 43

Community Outreach – Chronic Pain Patients 46

McMaster as a Centre of Culture of Pain Research 48

External Academic Collaborations 50

Industry Collaborations 51

of 52

The Michael G. DeGroote Institute for Pain Research and Care is a research-intensive centre of excellence on pain mechanisms, diagnosis and management, where innovation and change are guiding principles. By providing optimal conditions, the Institute fast-tracks transformative research from discovery to development of new treatments and therapies for chronic pain. The Institute is a driving force for generating new knowledge and for translating this knowledge to all stakeholders, including patients, health care professionals, the commercial sector, the public and policymakers. Innovation in education is a cornerstone to build capacity for future research. As innovators and pioneers, we in the Michael G. DeGroote Institute for Pain Research and Care boldly expand the frontiers of understanding, diagnosing and managing chronic debilitating pain. The ultimate goal is a world in which chronic pain can no longer be debilitating.

of 52

A TRIBUTE TO MR. DEGROOTE Since its inception in 2003, the Institute for Pain Research and Care

has engaged in groundbreaking basic research, initiated interdisciplinary collaborations, offered medical education opportunities and organized community outreach projects.

Undoubtedly, much of this urgent work would not be possible without the generosity and insight of Michael G. DeGroote. We

sincerely thank Mr. DeGroote for his unwavering commitment to the goal of understanding, and ultimately, overcoming chronic

pain.

of 52

National Pain Awareness Week “A large part of the problem is that chronic pain is so poorly understood. Scientists around the world are working to remedy this problem, and Canadians are world leaders in this field.” Honourable Senator Yves Morin, introducing a Private Member’s Bill in the Canadian Senate, declaring the first week of November each year as Pain Awareness Week. 28 October, 2004.

of 52

Vision

The Michael G. DeGroote Institute for Pain Research and Care is a research-intensive

centre of excellence on pain mechanisms, diagnosis and management, where innovation

and change are guiding principles. By providing optimal conditions, the Institute fast-

tracks transformative research from discovery to development of new treatments and

therapies for chronic pain. The Institute is a driving force for generating new knowledge

and for translating this knowledge to all stakeholders, including patients, health care

professionals, the commercial sector, the public and policymakers. Innovation in

knowledge translation and exchange is a cornerstone, to build capacity for future research.

As innovators and pioneers, we in the Michael G. DeGroote Institute for Pain Research

and Care boldly expand the frontiers of understanding, diagnosing and managing chronic

debilitating pain. The ultimate goal is a world without suffering from chronic pain.

of 52

Mission

- taking ownership of central post-stroke pain

- creating a new paradigm in the conceptualization and perception of chronic pain –

it must be recognized as a distinct disorder, deserving, in fact demanding, direct

treatment and management by pain specialists

- recruiting leaders in areas of pain research of strategic importance to the evolution

of the Institute

- providing outstanding research facilities to promote cutting-edge research

- forging, fertilizing and facilitating initiatives in pain research and care at

McMaster and more broadly throughout Canada

- establishing living collaborations and partnerships with all relevant academic and

non-academic stakeholders for mutual advancement

- building a network for integrated action among members and partnered

stakeholders

- developing novel interventions to treat chronic pain

- promoting evolution of improved approaches to management of chronic pain

- enhancing knowledge transfer to and application by all receptor communities

- generating and preserving sound operational principles to optimize investments in

the Institute

- leading innovation in knowledge translation and exchange

- attracting, training and retaining the very best of successive generations of young

investigators

- reaching out to the community to enhance understanding of chronic pain and its

management

- leading local, provincial and federal initiatives in pain research and care

- representing needs of consumers to policymakers, in partnership with consumer

and advocacy groups

of 52

Environmental scan

Pain is a necessary part of our normal physiology. It prevents tissue damage and causes

behavioural and physiological changes to facilitate tissue repair. However, for an

unfortunate few, pain can create debilitating unbearable suffering. For the majority, pain

is not a medical challenge. For the few it is. Pain is heterogeneous in terms of aetiology,

mechanisms and temporal characteristics, making it difficult to study other than through a

multidisciplinary approach focussed on selected types of pain. Also, it is clear that there

is no “magic bullet” to treat all types of pain. What is needed is to understand that

different types of pain exist (Woolf & Salter, 2000), the distinguishing properties of each

type (Schulz & Woolf, 2002) and an understanding of the mechanisms underlying each

type (Hunt & Mantyh, 2001; Decosterd et al, 2004). If we are to develop novel

interventions to treat chronic pain it is imperative to find the specific molecular targets of

different pains (Honore et al., 2000). Concepts of mechanisms also need to be partnered

with emerging views from genetics, genomics and proteomics of pain (Mogil &

McCarson, 2000; Mogil, 2004). Demographics indicating an ageing population

accentuate this need for innovative interventions to treat chronic pain (Gibson & Farrell,

2004); as the mean population age increases, the incidence of chronic diseases such as

rheumatoid arthritis, osteoarthritis, diabetes and others, all sharing the symptom of

debilitating chronic pain, are expected to skyrocket, and with them the need for effective

pain management (Ferrell, 2004).

of 52

Leadership

Dr. Henry, a neurophysiologist who has worked throughout his career to understand underlying mechanisms of chronic pain, is the inaugural scientific director of the Michael G. DeGroote Institute for Pain Research and Care at McMaster University. He also holds an endowed chair in central pain. Joining McMaster in January 2005 as a professor in the departments of Psychiatry and Behavioural Neurosciences and Anesthesia, he is also renowned for important advancements in basic science of pain, his strong record of leadership, and his training of young

investigators. Dr. Henry earned his doctorate in physiology from the University of Western Ontario in 1972 and received postdoctoral fellowships from the Canadian Medical Research Council and Le Conseil de la recherche en santé du Québec. In 2000 he was awarded the Millennium Distinguished Career Award of the Canadian Pain Society. From 1977 to 2002 he was a professor in the Department of Physiology at McGill University. He established both the McGill Centre for Research on Pain and the Quebec Pain Research Initiative which networks pain researchers and clinicians across Quebec. From 2002 to 2004, he was professor and chair of the Department of Physiology and Pharmacology at the University of Western Ontario. His research has a focus on control systems within the central nervous system. He is world renowned for his pioneering discovery, in 1975, that the peptide, substance P, is a regulator of synaptic transmission in central pain pathways, specifically in the region of the first sensory synapse in the spinal cord and brain stem. This discovery opened a new field of research into the neurochemistry of pain mechanisms and led him to propose a chemical specificity theory of pain that replaced previous theories of pain and which persists unchallenged today. His awards over the past ten years include the Millennium Distinguished Career Award of the Canadian Pain Society (2000), the Raymond W Houde Memorial Award of the Eastern Pain Society, New York (2006) and the Gunn-Loke Lecture, Multidisciplinary Pain Center, University of Washington (2008).

James L. Henry, Ph.D. Scientific Director

of 52

Dr. Panju is the first medical director of McMaster University ’s Michael G. DeGroote Institute for Pain Research and Care. He has also been appointed to the Medard DeGroote Chair in Medicine. He is the Vice Chair (Clinical), Department of Medicine at McMaster University. He is a co-lead for Chronic Disease Management and Prevention for Local Health Integrated Network. Dr. Panju, who is both a professor of medicine for McMaster’s Faculty of Health Sciences and has completed ten years as chief of medicine for Hamilton Health Sciences, has a particular interest in the mechanisms and treatment of pain, in addition to his interests in cardiology and thrombosis. Trained as a physician in Britain, Dr. Panju came to Canada in 1975 and worked as a family physician for five years in the Ontario communities of Ignace, Thunder Bay and Cambridge, before completing a residency in internal medicine with further training in cardiology and thrombosis at McMaster University in 1984. Dr. Panju has been a faculty member at McMaster since 1986 and his abilities as an instructor have been reflected in teaching awards he has received from students, medical residents and his academic peers. In 2003, he received the national Osler Award from the Canadian Society of Internal Medicine, as an individual who exemplified the best in medicine. Previously he earned the John C. Sibley Award from McMaster’s Faculty of Health Sciences for his outstanding contribution to health sciences education and research. Dr. Panju says his interest in pain was kindled by a challenging patient with thalamic pain. His investigation made it clear that there has been very little research being done in the field of thalamic and central pain. His research has focused on chest pain, cardiology, thrombosis and general internal medicine. He has over 50 publications to his credit, including contributions to book chapters and co-editing a book on Post

Stroke Central Pain, and he is a past-president of the Canadian Society of Internal Medicine. For the pain institute he will create and coordinate an international database and registry for patients suffering with thalamic and central pain. A key focus of the Michael G. DeGroote Institute for Pain Research and Care will be ensuring a collaborative approach in national and international research in pain. “The Michael G. DeGroote Institute for Pain Research and Care will be a hub and magnet to attract individuals of national and international stature in pain research activity,” he says. His responsibilities will include coordinating pain services locally and regionally and building the institute’s partnership with Hamilton Health Sciences. His recent research has focussed on evaluating a thermal grill instrument for management of different types of chronic pain.

Akbar Panju, M.D. Medical Director

of 52

Osteoarthritis Pain Research

Artist depiction of life with osteoarthritis pain. Osteoarthritis – what is it?

• Osteoarthritis is a degenerative joint disease and is the most prevalent form of arthritis

• Osteoarthritis is the leading cause of disability (MMWR Morb Mortal Wkly Rep. 50 (7): 120–5)

What is its impact? • approximately 10% of Canadian adults are afflicted with osteoarthritis (Health

Canada, 2003). • pain is reported to be what causes patients with OA to seek medical attention

(Creamer et al., 1998) • the primary goal of current management of the patient with OA remains

control of pain along with improvement in function and health-related quality of life (Felson, 2005)

• there is poor correlation of OA pain with radiographic and other signs in OA, such as loss of cartilage and bony changes (Lethbridge-Cejku et al., 1995)

• effectiveness of existing drug therapies for OA pain is poor, with only moderate effectiveness (Wieland et al., 2005)

• patients with OA are faced, then, with limited treatments that have a known mechanistic basis of action

• significant resources are being applied to limiting cartilage loss and alterations in bone structure, but until recently, there has been little basic science investigation focused on understanding the mechanisms underlying the initiation and the maintenance of the pain of OA

of 52

What are we contributing?

• studies to address the lack of mechanism-based treatments • several mechanisms of OA pain have been proposed, but none accounts for

o lack of correlation of functional and structural change o referred nature of OA pain o loss of proprioception

• we have established a unique animal model of OA pain o confirmed in histological, anatomical, imaging and physiological

studies • have found that joint use exacerbates joint pathology • have identified changes in gene expression in OA knee • studying changes in gene expression in sensory neurones • recording from spinal nociceptive neurones

o data indicate that the spinal substrate of nociception undergoes loss of buffering capacity

• recording from primary afferent neurones o data indicate that the primary pathology is not in normally nociceptive

neurones, but that large diameter non-nociceptive neurones undergo a phenotypic change and relay a ‘pain’ signal to spinal nociceptive neurones

• on the basis of our results we are proposing a new hypothesis of OA pain: that encompasses all symptoms associated with OA and departs from all earlier hypotheses on mechanisms of OA pain

• involved in commercial development of novel compounds for treatment of OA pain

of 52

Who is involved? This project is being carried out by Dr. Qi Wu , Dr. Kiran Yashpal and Yufang Wang, as well as collaborators Drs. Aexander Ball, Heather Arnett, Frank Beier and David Holdsworth.

Dr. Qi Wu received an M.D. degree in 1997 and an M.S, Anaesthesiology in 2000, from the Second Military Medical University, Shanghai, China. In 2005 he joined a graduate programme at McMaster and is currently a senior Ph.D. student running electrophysiological experiments on dorsal root ganglion neurones.

Three-dimensional reconstruction of micro-computed tomographic images of an osteoarthritic knee from a model animal.

of 52

Peripheral Neuropathic Pain Research

“Pain is a major healthcare problem in Europe. Although acute pain may reasonably be considered a symptom of disease or injury, chronic and recurrent pain is a specific healthcare problem, a disease in its own right”

European Federation of IASP Chapters

“Ten years following the initial neck injury I painted this self-portrait; a study in the unceasing coldness that set in after surgery and the continuing awareness of the area of

surgery, a self-consciousness about the resulting scar and the residual pain. This is despair and resignation combined with a determination that saw me through many years

of surgeries and pain and treatment yet to come. ”

Courtesy of the PAIN Exhibit and www.PainExhibit.com © 2007 Chronic Pain Visual Arts Project. All Rights

of 52

Peripheral neuropathic pain – what is it?

• peripheral neuropathic pain is due to damage or dysfunction to the peripheral nervous system

• types of peripheral neuropathic pain include: painful diabetic neuropathy, post-herpetic neuralgia, post-amputation pain, HIV-related neuropathies, chemotherapy-related neuropathies, complex regional pain syndrome, traumatic and compressive nerve injuries, nerve tumours including neuromas, trigeminal neuralgia, syringomyelia, failed back surgery syndrome, traumatic brachial plexus injury,

What is its impact?

• as much as 7% to 8% of the of the population is affected by neuropathic pain and in 5% it may be severe

• neuropathic pain is associated with a number of other comorbdities, including depression, sleep disorder and development of other types of pain, and is a major contributor to absenteeism and decreased productivity at work

• neuropathic pain is relatively refractory to medical treatment, with only 50% of patients achieving even modest pain relief

• mechanisms underlying peripheral neuropathic pain are unknown


• studies undertaken to address the lack of mechanism-based treatments • we have been running a unique animal model of peripheral neuropathic pain • measuring influence of neuronal dysfunction on pathology of peripheral tissues • reflex testing using standard tests of

o tactile hypersensitivity o mechanical hyperalgesia o cold place preference test o differential weight-bearing test

• recording from spinal nociceptive neurones o data indicate that the spinal substrate of nociception undergoes increased

excitation to noxious and innocuous stimuli • recording from primary afferent neurones

o data indicate that the primary pathology is not in normally nociceptive neurones, but that large diameter non-nociceptive neurones undergo a phenotypic change and relay a ‘pain’ signal to spinal nociceptive neurones

• mechanisms implicated specifically from our studies indicate substance P and other structure-related chemical pathways in peripheral neuropathic pain

• on the basis of our results we are proposing a new hypothesis of neuropathic pain that pain is due to mechanisms that evolve over days, giving a therapeutic window of “a golden day and a silver week”, after which the pain will be difficult to treat

• involved in commercial development of novel compounds for treatment of peripheral neuropathic pain

of 52

Who is involved? This project is being carried out by Liliane Dableh, YongFang Zhu, Yufang Wang and Dr. Kiran Yashpal as well as collaborators Drs. Alexander Ball and Steve Bain.

Liliane Dableh received her B.Sc. at the University of Toronto, with a specialization in Physiology and a minor in Life and Environmental Physics. She completed her M.Sc. under the supervision of Dr. James Henry, at McGill University. She is currently completing her Ph.D. in Dr. Henry’s lab at McMaster University. Her research is focused on early intervention after nerve injury as a means to prevent the development of neuropathic pain.

YongFang Zhu is currently in her second year of the Ph.D. Medical Sciences program at McMaster University. She has previously completed a Master’s degree in Biochemistry and Biomedical Science as well as Bachelor’s degrees in Biology and Computer Science. Yong Fang is very proud to be working for the Pain Institute and is working hard to become an excellent electrophysiologist.

of 52

Artist rendering of peripheral neuropathic pain


of 52

Central Post-stroke Pain Research

A wretched soul, bruised with adversity, We bid be quiet when we hear it cry; But were we burdened with like weight of pain, As much or more would we ourselves complain

The Comedy of Errors, Act 2, Scene.1, 34-7.

Self-portrait by artist with central post-stroke pain

From: http://www.painonline.com

of 52

Central post-stroke pain – what is it? CPSP occurs from stroke or cerebrovascular accident that injures the sensory thalamus or specific sensory pathways (spino-thalamo-cortical pathways) What is its impact?

• CPSP develops in 8% of stroke victims • burning seems to be the commonest descriptor of pain • most patients have more than one kind of pain • pain is moderate to severe at least in 50% of victims • appears immediately after stroke in more than 1/3 of patients, up to 12 months

later in half, 2 years in 9.5% and more than 2 yrs in 4.5% • accompanied by sensory abnormalities

o hypoesthesia o hyperesthesia o paresthesiae o dysesthesiae

• limited success with traditional neuropathic pharmacotherapy and opioids as well as deep brain stimulators


• we have established the first animal model of CPSP • have plotted the time course of development of tactile and cold hypersensitivity,

confirming parallel to the human condition • have measured the time course of apoptosis following stroke in the sensory

thalamus • have measured the time course of necrosis following stroke in the sensory

thalamus • have measured the time course of vascular permeability following stroke in the

sensory thalamus • have identified the changes in vascularization of the brain following stroke in the

sensory thalamus • have implicated nitric oxide synthase in early stages of CPSP • involved in commercial development of novel compounds for treatment of central

post-stroke pain

of 52

Who is involved? This project is being carried out by Dr. Kiran Yashpal, Vasek Pitelka and Yufang Wang, as well as collaborators Drs. David Holdsworth and Jose Nobrega.

Kiran Yashpal is an Academic Research Scientist at the Pain Institute. She obtained her PhD from the Montreal Neurological Institute at McGill University. She received a postdoctoral fellowship from the Canadian Heart and Stroke Foundation to study with Dr. Remi Quirion at McGill. She is best known for her behavioural and physiological reflex studies in rodent models of acute and chronic pain, as well as her work on the functional neuroanatomy of pain pathways. She recently designed an animal model of central post-stroke pain.

of 52

Rheumatoid Arthritis Pain Research Rheumatoid arthritis – what is it?

• rheumatoid arthritis is a painful inflammatory joint disease attributed to a systemic autoimmune disorder that causes the immune system to attack the joints – the cause is unknown

What is its impact?

• reported to affect approximately 1 % of the adult population worldwide • pain is a major disabling factor, leading to:

o limitations on quality of life o additional chronic health problems o substantial consumption of health care resources o loss of productivity in the workplace

• there is no known cure for RA although some disease-modifying drugs are available

• there are currently limited treatments for RA pain

What are we contributing? • studies to address the lack of mechanism-based treatments

• measuring neuronal influence on pathology of peripheral joint tissue

• recording from spinal nociceptive neurones o hyperexcitability of spinal nociceptive neurones o joint movement causes long-lasting excessive response to synaptic inputs

• mechanisms-based research o implicates nitric oxide synthase mechanisms in RA pain o implicates cycooxygenase mechanisms in RA ain o implicates growth factors in RA pain

• involved in commercial development of novel compounds for treatment of RA pain

of 52

Who is involved? This project is being carried out by Julie Mudryk and Dr. Kiran Yashpal.

Julie Mudryk recently completed an undergraduate degree in Health Sciences at the University of Ottawa. She is now pursuing a Master’s degree in the Medical Sciences program at McMaster under the supervision of Dr. Kiran Yashpal and Dr. James L. Henry. Her project involves the elucidation of nociceptive mechanisms and associated therapeutic treatments in rheumatoid arthritis.

of 52

Bone Cancer Pain Research

“The act of verbally expressing pain is a necessary prelude to the collective task of diminishing pain.”

Elaine Scarry

Artist rendering of diffuse pain


Bone cancer pain – what is it?

• bone cancer pain most commonly occurs when tumors originating in breast, prostate, or lung metastasize to long bones, spinal vertebrae, and/or pelvis

• bone pain is commonly the first symptom of bone metastases and may lead to tests that will confirm the diagnosis

• primary and metastatic cancers involving bone account for an estimated 40,000 new cancer cases per year in Canada

• >70% of patients with advanced breast or prostate cancer have skeletal metastases • pain resulting from bone cancer can dramatically impact an individual’s quality of

life • generally two major components to bone cancer pain

of 52

o an early dull ache or throbbing in character, usually ongoing and increases in severity over time

o a later breakthrough or incident pain occurs either spontaneously, with intermittent exacerbations of pain, or by movement of the cancerous bone - one of the most serious and highly debilitating sequelae of cancer and one of the most difficult cancer pains to treat

• radiotherapy remains the cornerstone for the treatment of bone cancer pain, it is most effective for the symptomatic treatment of local bone pain but is accompanied by severe adverse effects

• control of breakthrough pain can be problematic because doses required are usually high and accompanied by adverse side effects such as severe cognitive impairment, sedation, and constipation

• little is known about the mechanisms that generate and maintain this pain What is its impact?

• bone cancer pain significantly impacts quality of life • costs of metastatic bone disease are estimated at 17% of total oncology

expenditures • metastatic bone disease imposes a significant impact on the health care delivery

system What are we contributing?

• Dr. Gurmit Singh has established a unique animal model of bone cancer pain in which we are investigating mechanisms of pain

• as one of the first research groups to focus specifically on mechanisms of the pain associated with bone metastasis we are measuring nociceptive scores and administering analgesic agents to determine how this model parallels the human condition

• future studies will focus on the chemical basis of altered nociceptive mechanisms and the phenotypic changes that occur in sensory pathways

of 52

Who is involved? This project is being carried out by Paolo De Ciantis, Dr. Kiran Yashpal and Dr. Gurmit Singh.

Paolo De Ciantis obtained an Honours Bachelor of Science degree from the University of Toronto majoring in Life Science (Human Biology) and Sociology. He is currently completing a Master of Science degree in the Medical Sciences Graduate Program at McMaster under the co-supervision of Dr. Gurmit Singh and Dr. James L Henry. His time as a graduate student has been divided between research and extracurricular activities such as Co-president for the Health Science Graduate Student Federation (HSGSF) and sitting on the Graduate Policy and Curriculum Committee.

of 52

Dr, Gurmit Singh is a full professor in McMaster’s Department of Pathology & Molecular Medicine and an associate member of the departments of Biochemistry and Biology. A member of various international science societies, he has published over 100 papers and edited 3 books. He holds grants from National Institute of Health (US), Canadian Institute of Health Research, Canadian Breast Cancer Alliance, Cancer Research Society, and Ontario Cancer Research Network. His research focuses on experimental therapeutics with an emphasis on breast and prostate cancer. He was recruited to become the Juravinski Cancer Centre’s first Career Scientist in 1984 and initiate the Terry Fox Laboratories at McMaster with Dr. Bill Orr. He became Director of Research in 1993, and a Senior Scientist for Cancer Care Ontario in 1996.

of 52

Low Back Pain Research

“To experience pain is to have certainty; to hear about pain is to have doubt.”

Elaine Scarry

Low back pain Low back pain – what is it?

• back pain arises from trauma to the back or a disorder such as arthritis o a sports injury o work around the house or in the garden o sudden jolt such as a car accident o other stress on spinal bones and tissues

• nearly everyone at some point has back pain that interferes with work, routine daily activities, or recreation

of 52

What is its impact?

• back pain is the most common cause of job-related disability • back pain is the second most common neurological ailment • back pain costs the Canadian economy an estimated $5 billion annually • treatment involves using analgesics, reducing inflammation, restoring proper

function and strength to the back, and preventing recurrence of the injury • bed rest is NOT recommended for back pain • may be due to stress or pressure on dorsal roots • pain may be associated with

o loss of bowel or bladder control o pain when coughing o progressive weakness in the legs


• we have recently established a unique derangement animal model of low back pain

• have developed novel tests to measure low back pain in the rat o algometer-monitored vocalization o movement-induced hypersensitivity o side-to-side progression test

• movement-induced hypersensitivity confirms parallel to the human condition • histological approach to identify structural changes associated with the model • imaging to identify structural changes associated with the model • studying mechanisms underlying hypersensitivity

of 52

Who is involved? This project is being carried out by Prateek Kalani, Dr. Kiran Yashpal, Vasek Pitelka and collaborator Dr. Howard Vernon.

Prateek Kalani is presently enrolled in his fourth year of undergraduate studies in the (Honours) Bachelor of Health Sciences Program at McMaster University. He is currently undertaking a thesis project under the supervision Drs. Yashpal and Henry, studying and evaluating an animal model of lower back pain in rats.

of 52

Iconic Pain Assessment Tool

It is said that few die from pain; yet many die in pain and even more live in pain. What is the Iconic Pain Assessment Tool?

• unlike other major health disorders, there is a general lack of objective measures for pain, particularly chronic pain

• we are reliant on translation tools for the accurate and efficient interpretation of patient experience, which must operate within a user-friendly framework and demonstrate the properties of validity, reliability, and patient adherence

• an ideal pain assessment instrument should: o provide a quantitative measure for analysis o capture the different qualitative dimensions of pain o be free from reliance on linguistic competence o be related to the patient’s disease experience

of 52

REFERENCES McMahon E. (2006). The challenge of visualizing pain: a web-based educational module and iconic pain assessment tool targeted towards patients with central post-stroke pain. Master’s Research Paper. Biomedical Communications, University of Toronto. McMahon E, Wilson-Pauwels L, Henry JL, Jenkinson J, Sutherland B, Brierley M, BFA. The iconic pain assessment tool: facilitating the translation of pain sensations and improvising patient-physician dialogue. J Biocommunication (in press), 2008. What are we contributing?

• The Iconic Pain Assessment Tool (IPAT) was designed in 2006 by Emilie McMahon, a former graduate student in the Department of Biomedical Communication at the University of Toronto, co-supervised by Dr. Henry

• Features of the IPAT: freely accessible on the World Wide Web, facilitates the assessment of pain quality, intensity and location, four assessments available over the diurnal cycle, completed templates can compiled into a longitudinal record of pain status

• Central Hypothesis states that the IPAT is a valid and reliable instrument for the assessment of persistent pain

• Pilot Study: designed to assess the face and content validity of the IPAT

• Validation Study: intended to demonstrate the properties of criterion and construct validity, test-retest reliability and patient adherence

of 52

Who is involved? This project is being carried out by Chitra Lalloo and Dr. James L. Henry.

Chitra Lalloo completed her undergraduate studies in the Bachelor of Health Sciences Program at McMaster University in May 2008. She is currently pursuing a Master’s degree in the Medical Sciences Program under the supervision of Dr. James Henry. Her project involves the assessment and validation of an iconic pain assessment tool in a population of neuropathic pain patients. Chitra’s research is supported by the Alexander Graham Bell Canada Graduate Scholarship (NSERC).

of 52

Technical support for the research group

Sheila Bouseh, Senior technician, received a BSc. from Trinity College in Hartford, CT with a double major in Neuroscience and Psychology and a minor in Human Rights. She currently manages the Institute’s main laboratory.

Vasek Pitelka, Senior technician, oversees the laboratory at the University of Western Ontario and plays a leading role in several of the projects on-going at McMaster.

of 52

Elsa Mammen received a BSc. from Bharathiar University in India, majoring in Microbiology. She is a graduate of the Biotechnology diploma program at Centennial College in Scarborough. She is the newest member of the Henry lab, working as a research assistant.

Yu Fang Wang graduated from Shanghai Medical University in China with training as a nephrologist. She has been performing morphology work including immunohistochemistry and histochemistry for more than ten years since coming to McMaster University. She is currently working on dorsal root ganglion (DRG) and brain tis sues with Laser Scanning Confocal Microscopy in Dr. Henry’s lab.

of 52

Community Alliances for Health Research and Knowledge Translation in Pain This is a research project in knowledge translation funded by the CIHR Institute of Musculoskeletal Health and Arthritis and the CIHR Institute of Neuroscience Mental Health and Addiction.

Clause 4 of Bill C-13, the CIHR Act of the Canadian Parliament states:

“The objective of the CIHR is to excel, according to internationally accepted standards of scientific excellence, in the creation of new knowledge and its translation into

improved health for Canadians, more effective health services and products and a strengthened Canadian health care system …”

Research generating knowledge in pain is attempting to understand mechanisms, complexities, incidence and prevalence, the personal, social and economic costs, etc. While much remains to be learned, at the same time we must recognize that we are much further ahead than we were 20 years ago, even 10 years ago. An important question, though, is how much this mounting knowledge is being applied to those who suffer debilitating pain, which is the presumed end-purpose of knowledge generation. This is the entry point for ‘knowledge translation‘, the term widely used to refer to the process of research use, or the application of knowledge to receptor communities. More formally, knowledge translation at CIHR is defined as the exchange, synthesis and ethically sound application of research findings within a complex set of interactions among researchers and knowledge users - to accelerate the capture of the benefits of research for Canadians through improved health, more effective services and products, and a strengthened health care system. Canada, the Canadian health care system, Canadian society and the Canadian economy are in dire need of application of knowledge translation and exchange to debilitating pain. In fact, a national strategy is needed to promote implementation of research findings,

of 52

application and appraisal of clinical practice guidelines, and uptake of decision support tools by health care practitioners and decision-makers. What we are doing about it? CAHR-pain is a Canadian research network funded by the Canadian Institutes of Health Research to provide knowledge translation to receptor communities in the area of pain. The six themes are each led by internationally-recognized leaders in the field, and you are invited to learn about what each theme has as its research objectives, who the participants are in each research theme, what the respective receptor communities are, what the long-term objectives are and how these will be carried out. This information is available by clicking on the respective section of this web site. The overarching impact from the outputs of this CAHR is to promote and sustain a balanced portfolio of curiosity-based and needs-based research, which along with existing knowledge will be mobilized and applied for the benefit of Canadians, the health system and the economy. The value-added of the CAHR is as follows:

• Creation of a unified stakeholder voice to make recommendations for public and voluntary sector policy development to address the huge burden of chronic pain

• Creation of the defensible case for research-community interactions in this domain to ensure that reliable knowledge addresses burden by being socially robust

• Enhancement of the funding base supporting operations and, on this basis, potential for leverage from the public purse, for incremental funding

Chronic pain as a chronic disease

of 52

The burden of chronic diseases is tremendous, and traditional methods of healthcare delivery are unsuitable for addressing these needs. Chronic disease management has emerged as a new strategy for chronic disease care. Chronic disease management in the clinical setting is defined as an organized, proactive, multi-component, patient-cantered approach to healthcare delivery that involves all members of a defined population who have a specific disease entity (or a subpopulation with specific risk factors). Care is focused on, and integrated across the entire spectrum of the disease and its complications, the prevention of comorbid conditions, and relevant aspects of the delivery system. Essential components include identification of the population, implementation of clinical practice guidelines or other decision-making tools, implementation of additional patient-, provider-, or healthcare system-focused interventions, the use of clinical information systems, and the measurement and management of outcomes. The European Federation of IASP Chapters (International Association for the Study of Pain) views chronic pain as a disease, and they have successfully lobbied the European Parliament to declare chronic pain as a disease.

“Pain is a major healthcare problem in Europe. Although acute pain may reasonably be considered a symptom of disease or injury, chronic and recurrent pain is a specific healthcare problem, a disease in its own right”

Who is involved? The following are key leaders in the CAHR-pain initiative: Theme I – Drs. Sandra LeFort and Shirley Solberg, Memorial University of Newfoundland, Dr. Thomas Hadjistavropoulos, University of Regina. Theme II - Drs. Judy Watt-Watson, Judith Hunter, Michael McGillian and Leila Lax, University of Toronto. Theme III – Dr. Allan Gordon, University of Toronto. Theme IV – Dr. Paul Taenzer, University of Calgary and Dr. Saifee Rashiq, University of Alberta. Theme V – Drs. Joy MacDermid, Linda Woodhouse, Patricia Solomon, McMaster Theme VI – Dr. John Lavis, McMaster. Special Advisers – Dr. Linda Li, University of British Columbia, Dr. Peter Tugwell, University of Ottawa, and Drs. Anthony Levinson and Jean-Eric Tarride, McMaster.

of 52

An overview of the mandates of the respective Research Themes is as follows: CAHR-pain will build capacity integrating community through to decision, as a state of readiness to partner with process to improve the quality of life of those living with the burden of chronic pain. At a national meeting in 2006 that included academics, clinician researchers, pain management professionals, patients, epidemiologists, experts in KT, health economists and industry representatives, it was agreed that to make meaningful progress action must be taken to address the quality care gap for the one in five Canadians suffering chronic pain. This initiative will create a favourable environment to drive innovation in KT directed at improving measurable outcomes through six Research Themes within three operating principles. Research Theme 1 – “From the Ground Up: Alliances to Address Chronic Pain in the Community”. This Theme will engage communities of chronic pain sufferers and families, providers of health care and relevant organizations in participatory action research to explore the chronic pain experience, the interface of chronic pain patients/families with the health system, the needs of people with chronic pain, and perspectives about client, provider and system expectations regarding care. We will conduct an in-depth review of the scientific, policy and lay literature to identify existing resources and emerging technologies for both patients and providers of care, and best practice and models of community-based care for chronic pain Research Theme 2 – “E-learning interprofessional pain curriculum for pre-licensure health science students”. The overall objective is to improve the health of Canadians who are experiencing pain, through the development and evaluation of an E-learning pain curriculum for pre-licensure health science students in universities across Canada. This study will be developed to: develop an E-learning pain curriculum for pre-licensure health science students; evaluate its transferability to pre-licensure health science students in selected universities across Canada; develop KT strategies for implementation of this curriculum in each site, including facilitator training; implement a pilot study to evaluate the final curriculum product. Research Theme 3 – “Preceptorship Programmes in Pain Management - Longitudinal Evaluation of Pain Management Education in Medical Trainees through Undergraduate and Post Graduate Programs and Creating Pain Management Clinics Practicing Evidence-Based Standards of Care”. The present research project is to: intervene at different levels of the career development of physicians and other health care practitioners to measurably improve the skills and competencies in pain management both locally and nationally; measure the impact of our various preceptorship programs on the physicians that we educate, particularly in the field of Pain and Addiction; demonstrate that pain clinics can follow acceptable standards of care and document that these standards of care were influenced by this training. Research Theme 4 – “Partnering with the Alberta HTA Chronic Pain Ambassador Programme”. The project team is committed to evaluating the impact of the “Ambassador Workshop KT Strategy” on: provider knowledge of evidence-based assessment and treatment strategies; provider clinical practices/activities when working with patients with these symptoms; patient outcomes. The results of the initial study will

of 52

be used to plan a two group cluster randomized trial and additional cluster randomized controlled trials comparing the Ambassador program to other promising knowledge translation strategies. Research Theme 5 – “Integrating Evidence into Effective Collaborative Practice to Enhance Quality of Life”. The objective is to apply innovative KT strategies engaging the chronic pain community to effectively mobilize explicit and tacit knowledge to assist those living with chronic pain to attain the best possible quality-of-life. We will develop and evaluate: a push-out technology (MacPlus-P) to capture and push-out the best evidence on management of chronic pain to clinicians, patients and policy makers; a Community of Practice approach to mobilizing the tacit knowledge required to implement best practice in chronic pain management (including community-based and knowledge developed in our Themes / groups). Research Theme 6 – “Engaging in Knowledge Translation Through Deliberative Processes”. The project team proposes: to develop and test a simple tool to describe and evaluate key elements of deliberative processes that bring together public policymakers, health system managers, clinical leaders, consumer group representatives and others to discuss key challenges in responding to chronic pain (e.g., goals, group composition, and group process); and to conduct formative evaluations of all deliberative processes and after two and four years a summative evaluation of a concerted effort to match key design elements to particular contexts.

of 52

The research listed in this booklet was made possible through funding from the following:

of 52

Community Outreach – Health Care Professionals

“Who understands pain, knows medicine” –Sir William Osler

Rationale: Pain imposes a heavy burden on health care services across the board. The 1994-1995 National Population Health Survey indicated that 3.9 million Canadians, or 17% of the population over the age of 15, suffer chronic pain. Sadly, though training in pain management is barely alluded to in most health professional training programmes (veterinarian trainees are reported to average five times more training than the average for physician trainees). Although 40-65% of visits to family physicians have a pain component, patients typically report that communication with doctors is poor. In a study that attempted to quantify the total cost of chronic non-cancer pain to the Irish economy in 1995, a study from a sample of 95 patients estimated that chronic pain had already cost the economy £1.9 million by the time of their referral to a multidisciplinary pain clinic. A reportedly high use of specialist care by chronic pain patients has been attributed to the absence of a functioning primary care gate-keeping system for patient selection. Management of low back pain in a cohort of general practitioners in Ireland was not consistent with European clinical guideline recommendations and it was found that most of the costs incurred by the National Health Services were attributable to physician non-adherence. The information in this paragraph is presented in detail in Henry, Pain Research & Management (in press) 2008. Clearly, knowledge translation to health care professionals remains a high priority if we are to address the needs of those who live with chronic pain. Goals: The principal goal of the community outreach to health care professionals is to address the gap between evidence and practice. A secondary goal is to create visibility and credibility of the Michael G. DeGroote Institute for Pain Research and Care as a leader in continuing health education in chronic pain. What are we contributing? This initiative is addressing knowledge translation to family physicians, specialists, nurses, nurse practitioners, physiotherapists, pharmacists and other interested professionals. In particular, Continuing Health Education Courses are being held to address issues facing health care professionals vis a vis chronic pain management. Topics in these courses have covered early and effective assessment, dealing with the complex patient, use and abuse of opioids in pain management, focus on rehabilitation and life habits, cannabinoids as drug or weed, the multidisciplinary approach to pain management, addiction and drug-seeking vs. the bone fide need, alternative approaches to

of 52

pain management, interrelation of the family physician and the pain clinic, non-pharmacological approaches to pain management, interprofessional interaction, etc. To carry out this programme a series of continuing health education events has been held each year since the first year of the National Pain Awareness Week in 2005. Participation in these courses has consistently drawn 80 to 110 from across the health care spectrum. Distinguished speakers have been attracted to the Hamilton/Burlington area nationally and internationally to provide fertilisation of local health care professionals with new and advancing ideas. The annual Academic Pain Day poster for 2008 is found on the next page. In addition, continuing health education courses have been offered during the Global Day Against Pain, as declared collectively by the World Health Organization and the International Association for the Study of Pain (IASP). Other continuing health education courses have been held at other times throughout the year. These events have been made possible largely through industry partners and the Ontario Pain Foundation, which was established to promote educational activities in the local community. These events and courses have been organized and run by Dr. Kiran Yashpal and Dr. James L. Henry. In 2006 the Michael G. DeGroote Institute for Pain Research and Care held an two and a half day international meeting in Toronto on central neuropathic pain. This attracted the thought leaders on central neuropathic pain from around the world. Funding was provided from the IASP as that year’s IASP Research Symposium, as well as funding from a number of industry partners. Attendance included mainly researchers and physicians and the programme provided an update on mechanisms, diagnosis and management of central neuropathic pain, particularly central post-stroke pain. The proceedings were published as a book and circulated widely by the IASP Press.

of 52

Community Outreach – Chronic Pain Patients

“Knowing is not enough; we must apply.

Willing is not enough; we must do.” - Goethe

“This sculpture symbolizes being trapped by chronic pain. The rebar represents a prison and I am attempting a desperate escape by pushing my face through the bars but there is never an escape.”


Rationale: In 2005 a patient support group was established in the Hamilton/Burlington area. The first thought of doing so came from a chronic pain patient performance in Toronto, based on stories of patients who were associated with the Wasser Pain Management Centre in Mount Sinai Hospital in Toronto, directed by Dr. Allan Gordon. It was apparent that patients needed to express themselves, they had stories to tell and they gained benefit from being and working together. It became clear that traditional health care delivery was important and critical to these patients and that self-management courses were also important. However, beyond these

of 52

it appeared to us that socializing with peers was also important. This is not offered by other resources and it was decided to establish the local group. To achieve this, we set up a vehicle to fund these activities, the Ontario Pain Foundation; with a Board of Directors and an accounting firm to ensure compliance, the OPF functions to promote educational activities in the local communities. Reference to some of these activities is made in the previous section on CHEs. Goals: The principal goal of this initiative is to create community alliances for health research and knowledge translation in pain, engaging all stakeholders with an interest in chronic pain. A secondary goal is to create visibility for the Michael G. DeGroote Institute for Pain Research and Care as a community leader in the cause against chronic pain. What are we contributing? Initially, we worked with the Chronic Pain Association of Canada to incorporate established principles to set up a support group with a catchment area including Hamilton and Burlington, although some patients have come from Kitchener/Waterloo, Brampton, Mississauga and the Niagara/St. Catharines area. The group has monthly meetings, on Tuesday nights. Each event includes a period of social networking. In addition, meetings include invited speakers of special interest to chronic pain patients. Past speakers have included topics such as the physician approach to chronic pain, physiotherapy for chronic pain, principles of nutrition to lessen the burden of pain, principles of tai chi for those who suffer chronic pain, massage therapy for pain, natural healing approaches to lessen pain, the ins and outs of pharmaceuticals for pain, a programme in self-management for chronic pain, the science behind pain, traditional Chinese medicine for chronic pain, etc. Many meetings also have entertainment to lighten the atmosphere. In addition, the group is assembling stories of what it is to live with chronic pain and of their experiences with the health care system, the legal system, the insurance system as well as family and friends. An annual Public Forum is also held. In this case, in addition to the social networking there are invited speakers and exhibits of community organizations that relate to chronic pain. For example, this year invited speakers include the President of the Canadian Pain Coalition, the national organization of support groups and chronic pain sufferers, and a physician who also suffers chronic pain. Community organizations include those offering services to chronic pain sufferers. The Ontario Pain Foundation has also sent representatives of this support group to the Annual Meeting of the Canadian Pain Society to interact with a broader community of stakeholders and to bring back their own experiences to the group. These activities have been organized by Drs. Kiran Yashpal and James L. Henry.

of 52

McMaster as a Centre of Culture of Pain Research The generous gift to McMaster from Mr. DeGroote gave birth to the possibility of creating a world-class pain institute. To create such an institute it has been necessary to introduce to McMaster and Hamilton Health Sciences a culture of pain research. None had existed before. An advantage was that previous models existed at the time in Toronto and Montreal, and recruitment of the Scientific Director brought direct experience with creating a culture of pain research and a track record of success in doing so. In particular, a strategy was pursued to generate this culture from existing strengths. For example, the CIHR project on Community Alliances in Health Research, CAHR-pain, has enlisted the following researchers at McMaster in a unique blend of expertise, creating a McMaster team of 8 researchers to include Drs. Brian Haynes, John Lavis, Anthony Levinson, Joy Macdermid, Patty Solomon, Jean-Eric Tarride, Linda Woodhouse. In addition, a number of other research projects have been launched to create a pain research culture from existing strengths. These include the following McMaster researchers. Dr. Alexander Ball is collaborating on immunohistochemical studies on intracellularly-labelled dorsal root ganglion neurones in an entirely unique technical approach to understanding mechanisms of the pain of osteoarthritis.

Drs. Norm Buckley and Akbar Panju – To 2007 I co-supervised a graduate student to develop an internet-based pain assessment tool for central post-stroke pain. This tool is found at the following URL: http://www.emiliemcmahon.ca/mrp.html - together with Drs. Buckley and Panju, we completed a research project, beginning with a summer student project last summer, to determine the most appropriate receptor community for this tool and then to refine the tool for these end users and monitor its uptake and effectiveness for patients and managers of central post-stroke pain. Ultimately, this tool will be broadened for application to other types of chronic pain.

Dr. Margaret Fahnestock has been collaborating on a study of the involvement of brain-derived neurotrophic factor (BDNF) in mechanisms of altered nociceptive mechanisms in the spinal cord of our animal model of osteoarthritis.

Dr. Jan Huizinga is collaborating on a highly technical and unique project. In this case, we will be recording intracellularly from single dorsal root ganglion neurones and classifying these neurones in terms of their electrophysiological and physiological properties. Each neurone will be individually filled by intracellular injection of a cellular marker. The ganglion will be removed, the neurones dispersed and the filled neurone will be extracted. This neurone will then be analyzed using RT-PCR to determine changes in expression, particularly of ion channel species. This is because of some unique observations we have made that have led to a new and transformative hypothesis that explains how osteoarthritis

of 52

pain is brought about and how this type of pain remains refractory to medical treatment. The plan is to carry out pilot experiments and submit a joint grant application for this project.

Dr. Wolfgang Kunze is collaborating on another highly technical and unique project. We will be recording intracellularly from single dorsal root ganglion neurones and classifying these neurones in terms of their electrophysiological and physiological properties. Each neurone will be individually filled by intracellular injection of a visible dye, the ganglion removed and placed into an in vitro recording chamber. The neurone will then be re-visualized and recorded from using patch clamp technology to determine the ion species underlying the changes in excitability and neuronal properties identified in our osteoarthritis model. The plan is to carry out pilot experiments and submit a joint grant application for this project.

Dr. Carl Richards – Our collaboration focuses on molecular mechanisms of inflammation and pain in osteoarthritis, using our derangement rat model of osteoarthritis. Based on some of our recent data, our laboratory is proposing that the pain of osteoarthritis arises from a demyelination process in peripheral nerve fibres, and this collaboration is directed at determining the role of cytokines and cytokine receptors in this process, including the breakdown of the connective tissue matrix that insulates these fibres and also provides the basis for saltatory conduction in these fibres, and that shares a symbiotic metabolic relationship with nerve fibres.

Dr. Gurmit Singh is collaborating on a study on an animal model of bone cancer pain. The project involves running physiological nociceptive reflex tests on these animals and running unique operant behavioural tests to measure the level of pain experienced. This model will be used to identify novel targets for development of new and effective treatment of bone cancer pain. A new graduate student has been taken on for this project.

Dr. Linda Woodhouse is collaborating on a study to develop a unique animal model of axial pain. Most animal models pertain to distal pains, yet the most common of the debilitating pains is axial. In this study we are expanding on the joint derangement of the osteoarthritis model and modifying an existing spine immobilization model to create a flexible derangement model of vertebral pain. This study also involves Dr. Kiran Yashpal as well as Drs. Barry Sessle and James Hu, of the University of Toronto, and Dr. Howie Vernon, of the Canadian Memorial Chiropractic College. The plan is to carry out pilot experiments and submit a joint grant application for this project.

of 52

External Academic Collaborations Beyond the direct benefits of collaborations with research laboratories at other research centres, the Michael G. DeGroote Institute for Pain Research and Care is gaining widespread visibility as an eminent centre in this field. The following collaborations have on-going research projects on pain mechanisms.

• Dr. Heather Arnett, Amgen Corp., Seattle WA, USA – gene expression analysis in dorsal root ganglion neurones in an animal model of osteoarthritis

• Dr. Steve Bain, University of Washington, Seattle WA, USA – changes in bone

structure in an animal model of neuropathic pain

• Dr. Frank Beier, University of Western Ontario – gene expression analysis in knee structures in an animal model of osteoarthritis

• Dr. Jean-Paul Collet, University of British Columbia, and Dr. Mark White,

Canadian Institute for the Relief of Pain and Disability, Vancouver - a pilot randomized controlled trial assessing the effectiveness of intramuscular stimulation to treat chronic low back pain associated with peripheral neuropathy

• Drs. Allan Gordon and Judy Watt-Watson, University of Toronto – learning

preferences in continuing health education courses

• Dr. David Holdsworth, Robarts Research Institute, London ON – imaging the time course and development of structural change in an animal model of osteoarthritis

• Dr. Myron Levin, University of Colorado, Denver CO, USA – neuronal

subpopulations involved in herpes zoster activation and generation of post-herpetic neuralgia

• Dr. Ed Lui, University of Western Ontario physiological studies on effects and

on mechanisms of action of ginseng in animal models of pain and of inflammation

• Dr. Saifee Rashiq, University of Alberta, and Dr. Mark Ware, McGill University

– clinical study on intramuscular stimulation intervention on clinical signs of neck torticollis

• Dr. Hee-Jeong Im Sampen, Rush University Medical Center, Chicago IL, USA –

a prospective clinical study, “Dynamic Interactions Between Joint And Spinal Cord Neurons In Knee Joint Pain”

• Dr. Howard Vernon, Canadian Memorial Chiropractic College, Toronto, and Dr.

Barry Sessle, University of Toronto – sensory-motor changes in an animal model of facet joint derangement, studies directed to mechanisms of axial pains

of 52

Industry Collaborations for Drug Development and Drug Testing Knowledge translation includes the application of fundamental knowledge to new techniques, methodologies, as well as new therapeutic approaches and tools. On-going collaborations on research projects as well as on product efficacy and development have been established with a number of industry partners, including:

Amgen Corp. – osteoarthritis pain

Merck Frosst – painful diabetic neuropathy

NeurAxon Inc. – central post-stroke pain

Pfizer Canada – neuropathic pain

Michael G. DeGroote Institute for Pain Research and Carefhs.mcmaster.ca/paininstitute/documents/Open...

Documents

Transcript of Michael G. DeGroote Institute for Pain Research and Carefhs.mcmaster.ca/paininstitute/documents/Open...