Pain | Opioids | glia

Research to improve the lives of those living with chronic pain.

The Problem of Pain

Chronic pain is pervasive and afflicts 1 in 5 adult Canadians. As the population ages and modern medicine allows people to survive serious illness, that number is expected to swell to 1 in 3. Chronic pain also affects young children, with 6–8% of children in Canada living with intense and frequent pain. That the problem of chronic pain persists, and is growing, is striking and highlights a major gap in our understanding of the fundamental neurobiology of pain.

Our work aims to answer key questions such as: How does our body tell us something is painful? Why do certain people go on to develop chronic pain whereas others, with apparently similar disorders or injuries, do not? Why is pain so difficult to treat? And how do opioids, which are the mainstay of pain therapy, cause their side effects?

To begin to unravel the paradox of pain, our research focuses on discovering the fundamental molecules and processes involved in chronic pain and enhancing the utility of opioid drugs in treating pain conditions. A strong focus of our research is the role of an understudied class of cells known as microglia, which are immune cells in the central nervous system, and the complex interplay between microglia and neurons in chronic pain and opioid analgesia.

Our Research Themes

1) Neurobiology of acute and chronic pain

2) Neurobiology of microglia (immune cells in the brain and spinal cord)

3) Opioid therapy and unwanted side effects associated with opioids

1. Brain and Spinal Cord - made with spinal cord sections and brain slices.png

TECHNIQUES

To study the cellular mysteries of pain, we use a range of techniques that encompass biochemical, molecular, live cell imaging, and behavioural manipulations. Cutting edge technology enables us to employ an integrative and comprehensive approach to dissect the key genes and proteins that drive chronic pain at the single cell and whole systems level.

Meet the Team

Featured

Dr. Tuan Trang, PhD

Professor

Dr. Churmy Fan, PhD

Research Technician

Dr. Erika Harding, PhD

Postdoctoral Fellow

Dr. Brendan McAllister

Postdoctoral Fellow

Dr. Aliny Pereira de Vasconcelos PhD

Postdoctoral Fellow

Sierra Stokes-Heck

Graduate student

Dr. Nynke Van Den Hoogen, PhD

Postdoctoral Fellow

Holly Vogel

Graduate student

Dr. Julia Canet Pons, PhD

Postdoctoral Fellow

Past Members

Kira Werder (Intern 2022)

Chloe Davidson (MSc 2021-2022)

Dr. Charlie Kwok (PDF 2016-2022)

Dr. Yuta Kohro (Visiting Professor 2019-2022)

Lauren Coulombe (Thesis Student 2020-2021)

Kristina Komarek (MSc 2017-2020)

Jeff Kates (Thesis Student 2018-2019)

Sydney Sparanese (Thesis Student 2018-2019)

Dr. Michael Mousseau (PhD 2013-2018)

Dr. Nicole Burma (PhD 2013-2018; MD 2021)

Dr. Nikita Burke (PDF 2015-2017)

Dr. Heather Leduc-Pessah (PhD 2012-2017; MD 2020)

Rebecca Dalgarno (MSc 2015-2017)

Cynthia Xu (MSc 2015-2017)

Rachel Redick (DVM Summer Student 2017)

Ally Pilapil (MSc 2014-2016)

Zoe Cairncross (Summer Student 2014-2015)

Jordan Haidey (Summer Student 2015)

David Lau (Summer Student 2014)

Joanna Rybicka (DVM Summer Student 2013)

Recent publications

Featured

Tackling the opioid crisis: Novel mechanisms and clinical perspectives

Leduc-Pessah, H., Trang, T. (2022)

Cannabinoids in Chronic Pain: Therapeutic Potential Through Microglia Modulation

van den Hoogen, N.J., Harding, E.K., Davidson, C.E.D., Trang, T. (2022)

Spinal A 3 adenosine receptor activation acutely restores morphine antinociception in opioid tolerant male rats

Leduc-Pessah, H., Xu, C., Fan, C.Y., Dalgarno, R., Kohro, Y., Sparanese, S., Burke, N.N., Jacobson, K.A., Altier, C., Salvemini, D., Trang, T. (2022)

Maternal and iatrogenic neonatal opioid withdrawal syndrome: Differences and similarities in recognition, management, and consequences

Isaac, L., van den Hoogen, N.J., Habib, S., Trang, T. (2022)

Role of Primary Afferents in Arthritis Induced Spinal Microglial Reactivity.

Kwok, C.H.T., Kohro, Y., Mousseau, M., O'Brien, M.S., Matyas, J.R., McDougall, J.J., Trang, T. (2021)

Identifying the Neurodevelopmental Differences of Opioid Withdrawal

van den Hoogen, N.J., Kwok, C.H.T., Trang, T. (2021)

Spinal interleukin-6 contributes to central sensitisation and persistent pain hypersensitivity in a model of juvenile idiopathic arthritis

Kwok, C.H.T., Learoyd, A.E., Canet-Pons, J., Trang, T., Fitzgerald, M. (2020)

Chapter 18: Changing Pain – Opioids and Pain. Dynamics of Pain. (Ed. Robert Sorge), Great River Learning.

Harding, E., Kwok, C.H.T., Trang, T. (2020)

Pannexin-1 channels as a therapeutic target: structure, inhibition, and outlook

Navis, K., Fan, C.Y., Trang, T., Thompson, R.J., Derksen, D. (2020)

Dopamine control of perinatal mammalian spinal network function is predominantly inhibitory

Sharples, S.A., Burma, N.E., Borowska-Fielding, J., Kwok, C.H.T., Eaton, S.E.A., Baker, G., Jean-Xavier, C.J., Zhang, Y., Trang, T., Whelan, P.J. (2020)

Chronic morphine-induced changes in signaling at the A3 adenosine receptor contribute to morphine-induced hyperalgesia, tolerance, and withdrawal

Doyle, T., Largent-Milnes, T., Chen, Z., Staikopoulos, V., Esposito, E., Dalgarno, R., Fan, C., Tosh, D., Cuzzocrea, S., Jacobson, K., Trang, T., Hutchinson, M., Bennett, M., Vanderah, T., and Salvemini, D. (2020)

Activation of the mu-opioid receptor by morphine promotes a PKCβ dependent potentiation of the TRPM8 channel

Iftinca, M., Basso, L., Flynn, R., Kwok, C.H.T, Roland, C., Ramachandran, R., Trang, T., Altier, C. (2019)

TRPV1 Promotes Opioid Analgesia During Inflammation

Basso, L., Aboushousha, R., Fan, C.Y., Iftinca, M., Melo, H., Flynn, R. Agosti, F., Hollenberg, M.D., Thompson, R., Bourinet, E., Trang, T., Altier, C. (2019)

Kappa Opioid Receptors Drive a Tonic Aversive Component of Chronic Pain

Liu, S., Pickens, S., Burma, N.E., Ibarra-Lecue, I., Yang, H., Xue, L., Cook, C., Hakimian, J.K., Severino, A.L., Lueptow, L., Komarek, K., Taylor, A.M.W., Olmstead, M.C., Carool, F.I., Bass, C.E., Andrews, A.M., Walwyn, W., Trang, T., Evans, C.J., Leslie, F.M., Cahill, C.M. (2019)

Microglial pannexin-1 channel activation is a spinal determinant of joint pain

Mousseau, M., Burma, N.E., Lee, K., Leduc-Pessah H., Kwok, C.H.T., Reid, A.R., O'Brien, M., Sagalajev, B., Stratton, J.A., Patrick, N., Stemkowski, P.L., Biernaskie, J., Zamponi, G.W., Salo, P., McDougall, J.J., Prescott, S., Matyas, J.R., Trang, T. (2018)

Intrathecal delivery of a palmitoylated peptide targeting Y382-384 within the P2X7 receptor alleviates neuropathic pain

Dalgarno, R., Leduc-Pessah H. (co-first author), Pilapil, A., Kwok, C.H.T., Trang, T. (2018)

Microglial P2X4R-evoked pain hypersensitivity is sexually dimorphic in rats

Mapplebeck, J.C.S., Dalgarno, R. (co-first author), Moriarty, O., Beggs, S., Tu, Y., Kwok, C.H.T., Mogil, J.S., Trang, T., Salter, M.W. (2018)

Macrophages Regulate Schwann Cell Maturation after Nerve Injury

Stratton, J. A., Holmes, A., Rosin, N.L., Sinha, S., Vohra, M., Burma, N. E., Trang, T., Midha, R., Biernaskie, J. (2018)

Site-specific regulation of P2X7 receptor function in microglia gates morphine analgesic tolerance

Leduc-Pessah H., Weilinger, N.L., Fan, C.Y., Burma, N.E., Thompson, R.J., Trang, T. (2017)

Neonatal injury results in sex-dependent nociceptive hypersensitivity and social behavioural deficits during adolescence, without altering morphine response

Burke, N.N., Trang, T. (2017)

Genetic deletion of microglial pannexin-1 attenuates morphine withdrawal, but not analgesic tolerance or hyperalgesia in mice

Burma, N.E., Leduc-Pessah, H., Trang, T. (2017)

Therapies and mechanisms of opioid withdrawal

Burma, N.E., Kwok, C.H.T., Trang, T. (2017)

Pain: From genes and proteins to cells in the living organism

Kwok, C.H.T., Trang, T. (2017)

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents

Burma, N.E., Bonin, R.P., Leduc-Pessah, H., Baimel, C., Cairncross Z.F., Mousseau, M., Vijaya Shankara, J., Stemkowski, P.L., Baimoukhametova, D., Bains, J.S., Antle, M.C., Zamponi, G.W., Cahill, C.M., Borgland, S.L., De Koninck, Y., Trang, T. (2017)