Research and Education Highlights

Diurnal variations in chronic pain are mediated by glucocorticoid regulation of ATP

Posted on 09-11-2016 — Diurnal variations in symptoms of chronic pain patients have been widely reported. However, the underlying mechanisms for this phenonemon have yet to be delineated. UTCSP scientist Michael Salter has collaborated with scientists in Japan to help reveal the molecular mechanisms underlying diurnal variations in pain hypersensitivity.

Targeting adenylyl cyclase in bone cancer pain

Posted on 09-11-2016 — Scientists in China have collaborated with UTCSP scientist Min Zhuo to investigate the potential mechanisms of bone cancer pain, a greatly understudied form of chronic pain. Patients with bone cancer experience severe pain at the site of the cancerous tumour, manifesting as continuous and/or spontaneous pain, and allodynia. This pain often becomes worse as the cancer progresses, greatly decreasing patient quality of life. Previous studies of other types of chronic pain have shown a role of the anterior cingulate cortex (ACC) and a compound called adenylyl cyclase (AC) in the development of the chronic pain condition. AC is activated when a neuron is very active, which triggers the production of cAMP and PKA, two second messengers involved in increased gene transcription and translation. This process works to increase glutamate receptor expression at the post-synaptic membrane, effectively potentiating synapses and increasing the fidelity of pain signals reaching the brain. In this study, the authors sought to determine whether this AC cascade in the ACC is also occurring in bone cancer pain models.

Variability in fMRI BOLD signal is a novel indicator of pain sensitivity and coping

Posted on 28-09-2016 — Dr. Karen Davis and PhD student Anton Rogachov have recently discovered that regional blood oxygen level-dependent (BOLD) signal variability is a novel indicator of pain sensitivity and coping. Published online by PAIN in July, this study is the first to demonstrate a link between neural signal variability and an individual’s acute pain sensitivity and ability to cope with pain.

Connaught Summer Institute in Pain keynote lecture: Inhibition of tetrahydrobiopterin synthesis alleviates neuropathic and inflammatory pain

Posted on 28-09-2016 — The Connaught Summer Institute in Pain brought pain research trainees from across the globe to Toronto to learn about the integration of research and clinical practice. The weeklong pain school culminated in a scientific meeting with keynote speaker Dr. Clifford Woolf, a renowned preclinical pain researcher based out of Boston Children's Hospital and Harvard University. Dr. Woolf discussed his recent research published in Neuron which highlighted the potential viability of targeting the tetrahydrobiopterin (BH4) synthesis pathway to treat inflammatory and neuropathic pain in humans.

Cognitive Behavioural Training for Pain: Does it Change your Brain?

Posted on 06-05-2016 — UTCSP member Dr. Karen Davis and her colleagues, Drs. Aaron Kucyi and Tim Salomons, recently reported in PAIN on differences in the brain function of healthy individuals via fMRI before and after cognitive behavioural training and repeated painful heat stimulus application.

Poor Pain Outcomes After Musculoskeletal Surgery Can Be Predicted By Post-Injury Anxiety and PTSD

Posted on 06-05-2016 — New clinical research from UTCSP members Dr. Colin McCartney and Dr. Joel Katz, and PhD candidate Brittany Rosenbloom helps to shed light on the vulnerabilities in patients that may predispose them to have poor pain outcomes, including development of chronic neuropathic pain.

The Periaqueductal Gray Matter: Sub-regions and Functional Connectivity with Descending Pain Modulation Circuitry

Posted on 16-03-2016 — The experience of pain is highly variable between individuals for a multitude of physiological and psychological reasons. Evidence now suggests that part of this variability is due to interactions between ascending nociceptive signaling pathways and descending modulatory circuitry. The periaqueductal gray matter (PAG) is a critical brain region involved in top-down modulatory circuits. The laboratory of Dr. Karen Davis, and post-doctoral fellow Dr. Marie-Andree Colulombe recently investigated sub-regions of the PAG and their functional connectivity with other brain regions involved in pain processing.

Neural Mechanisms Underlying Anxiety-Chronic Pain Interactions

Posted on 16-03-2016 — In a recent article in Trends in Neuroscience, Dr. Min Zhuo discusses the link between anxiety and chronic pain. While chronic pain and anxiety are often comorbid, and treating anxiety can result in a reduction in pain, these conditions are usually studied separately. Dr. Zhuo proposes that these conditions are related via long-term potentiation (LTP) mechanisms in the anterior cingulate cortex (ACC).

Abnormal cross-network functional connectivity in chronic pain and its association with clinical symptoms

Posted on 20-01-2016 — Kasey Hemington, Keith Wu, Aaron Kucyi, Robert Inman and Karen Davis recently published a neuroimaging study, characterizing abnormalities between functional brain networks in chronic pain patients. The authors used resting state, functional magnetic resonance imaging to uncover abnormal connections between functional networks that were closely related to clinical symptom severity.

Longitudinal Study of Catastrophizing, Pain and Cortical Thickness in Chronic Pain Patients

Posted on 20-01-2016 — Neuropathic pain is a common chronic pain condition, which occurs following peripheral nerve injury (PNI). It is currently unknown why only some individuals with PNI develop chronic pain. However, it is predicted that both biological and psychological factors contribute to this process. The laboratory of Dr. Karen Davis recently conducted a longitudinal investigation of pan catastrophizing (i.e., when an individual has exaggerated negative thinking about painful experiences) and insula gray matter changes in patients with nerve injury.

Preventing chronic post-surgical pain through the Toronto General Hospital Transitional Pain Service

Posted on 23-11-2015 — Chronic postsurgical pain can develop in 5-10% of patients within a year of surgery. Chronic post-surgical pain is difficult to treat, and results in poor patient outcomes, including loss of work, increased medical leave, and loss of quality of life. The global annual cost of chronic post-surgical pain has been estimated in the billions of dollars, underscoring the need for better treatment for post-surgical pain.

Efficacy of celecoxib in the treatment of chronic nonspecific low back pain

Posted on 19-11-2015 — Dr. Robert D. Inman’s research group has demonstrated that celecoxib, a non-steroidal anti-inflammatory drug, which selectively inhibits COX-2, has superior efficacy as compared to acetaminophen in treating chronic nonspecific low back pain. Dr. Inman conducted a randomized controlled trial to compare the effects of a 4-week treatment of either celecoxib (200mg, 2x daily) or acetaminophen (500mg, 2x daily) on both pain scores and MRI scores in 50 patients with nonspecific low back pain. Patients receiving celecoxib had more relief of total back pain and nocturnal back pain as well as more significant improvements on disability measures and global assessment measures than patients receiving acetaminophen. Neither celecoxib nor acetaminophen treatment produced any changes on MRI scores of inflammatory lesions nor morning stiffness, suggesting that both treatments are only effective at reducing pain scores.

A New Method to Detect Dishonesty in Self-Report Measures of Pain

Posted on 18-09-2015 — Self-report is the most valid and frequently used measure of pain in both clinical and research settings. However, some individuals may be inclined to provide deceitful self-reports in certain situations (e.g. insurance fraud). Thus, it is desirable to have a reliable method to detect dishonesty in self-report. Recently, UTCSP alumni Dr. Aaron Kucyi demonstrated that the use of sensory interference during self-report may be a potential tool to identify feigned self-reports.

Different Mechanisms of Spinal Cord Neuron Disinhibition in Neuropathic Pain Models Require Different Therapeutic Interventions

Posted on 18-09-2015 — Exciting new research from Dr. Steven Prescott’s lab is working to bridge the gap between basic research on neuropathic pain etiology to possible clinical interventions to treat neuropathic pain. Dr. Steven Prescott is a UTCSP member and scientist at the Hospital for Sick Children. In this paper, lead author Dr. Kwan Lee uses a unique method to measure intact spinal cord neurons from alive, anaesthetized animals, overcoming disadvantages of ex-vivo methodologies.

Individual Differences In Temporal Summation Of Pain Are Associated With Brain Connectivity

Posted on 20-07-2015 — In a recent article in the Journal of Neuroscience, the lab of Dr. Karen Davis and UTCSP trainee member Joshua Cheng reported on their study of the association of temporal summation of pain (TSP) responses with structural differences in projections contributing to pain perception. TSP is characterized by an increased perception of pain resulting from a repeatedly administered painful stimulus. Previous research has reported significant individual differences in TSP. 

Sex Differences In The Spinal Mechanisms Mediating Neuropathic Pain -- Implications Ror Pre-clinical Research

Posted on 20-07-2015 — In a recently published article in Nature Neuroscience, the laboratory of Dr. Michael Salter and UTCSP trainee member Josiane Mapplebeck reported that female and male mice use different mechanisms in the mediation of neuropathic pain. Previous research has shown that microglia, a type of cell involved in neuroinflammatory processes, mediate pain hypersensitivity resulting from nerve injury. However, evidence for the role of microglia in neuropathic pain is based on pre-clinical research conducted predominantly using male rodents.  Consequently, Dr. Salter, in collaboration with Dr. Jeffrey Mogil at McGill University, investigated the spinal mechanisms mediating neuropathic pain in females. 

Diffusivity signatures characterize trigeminal neuralgia associated with multiple sclerosis

Posted on 19-05-2015 — Trigeminal neuralgia (TN) is described as a neuropathic pain disorder characterized by severe, lancinating, facial pain with no sensory deficits. This pain occurs in the fifth cranial nerve, typically at the root entry zone, in response to stimuli as innocuous as light brush or touch of the skin. Patients with MS are 20 times more likely than the general population to develop TN. However, the pathophysiology of MS-TN is unclear and may involve central nervous system demyelination. Thus, understanding the microstructural anatomy of trigeminal fibres is essential to determining the etiology of MS-TN, and how best to treat it. 

p38 MAPK Mediates the Increased Risk of Persistent Postsurgical Pain in Adults Who Experienced Neonatal Injury

Posted on 19-05-2015 —

Research is emerging that pre-term babies carry certain susceptibilities with them into adult life. Pre-term babies typically undergo many surgeries and incisions at a time when the peripheral nervous system is still developing; and it seems that even small insults to the body can have major effects on the development of these sensory systems. It has previously been shown that when pre-term babies grow up they have a greater sensitivity to noxious stimuli, greater pain intensity after surgery, and are at a greater risk for developing persistent postsurgical pain. However, the mechanisms behind this phenomenon are unknown.

A new view on pain and the brain: Defining the dynamic pain connectome

Posted on 02-03-2015 — UTCSP members Dr. Karen Davis, Senior Scientist at Toronto Western Research Institute; and Dr. Aaron Kucyi, a former PhD student in Dr. Davis’s lab, have fully defined the dynamic ‘pain connectome’ in a review recently published in Trends in Neurosciences. The authors elaborate on their recent work on pain and attention interactions, and address the need for a fresh perspective on pain in the brain.

A Synaptic Mechanism for the Interaction between Anxiety and Chronic Pain

Posted on 02-03-2015 — UTCSP scientist Dr. Min Zhuo has published exciting new research with a possible explanation for the interdependence of anxiety and chronic pain. It has been previously shown that chronic pain increases the incidence and severity of anxiety, and similarly, that those with anxiety are more predisposed to having more severe symptoms.