Geoffroy Laumet, Ph.D.
Dr. Laumet’s lab interest is focused on understanding the neurobiology of chronic pain. Improving our understanding of how pain transitions from acute to chronic will facilitate the development of novel disease-modifying drugs. Thereby improve the quality of life of those who suffer from chronic pain. Today, it affects between 11%–40% of North Americans. Chronic pain drastically impacts the quality of life, is frequently associated with mood disorders and is an expensive public health condition. Our inability to manage chronic pain gave birth to the opioid crisis.
Pain is an unpleasant sensory and emotional experience which is essential for our survival as it protects us or our body from injury. Pain is common in response to injury and in many pathological conditions. Usually, pain will resolve when the wound is healed or the disease cured. However, in a significant subset of patients, it fails to resolve and the patients develop chronic pain. Chronic pain is not simply a continuum of acute pain, the transition from acute to chronic pain requires persisting adaptations that govern the long-lasting plasticity of the nervous system.
In our laboratory, we use mouse models to decipher the molecular and cellular mechanisms underlying the transition from acute to chronic pain. We model pain states induced by injury, surgery, cancer, inflammation, or chemotherapy treatment to investigate how these insults disturb the plasticity of the somatosensory system with a focus on two mechanisms: neuro-immune interactions and epigenetics.
Neuro-immune interactions in chronic pain. Increasing evidence indicate that non-neuronal cells (such as immune cells) critically contribute to the transition from acute to chronic pain. Activated immune cells release pro-inflammatory factors which sensitize neurons leading to increased pain signaling. Less studied, but likely equally important is the role of anti-inflammatory immune cells in the resolution of pain. We are currently investigating the role of the anti-inflammatory cytokine interleukin-10 in the remission and relapse of neuropathic and postoperative pain.
Epigenetics of chronic pain. Epigenetic mechanisms enhance or suppress gene expression without alterating (or: without a need for alterations in) the primary DNA sequence. These mechanisms include DNA methylation, histone modification, and expression of non-coding RNAs. Epigenetic mechanisms can be dynamic and responsive to changes in experience, representing a complex interplay between an organism and its environment. We previously showed that epigenetic changes orchestrate large-scale gene expression changes in injured sensory neurons, including genes important for neuronal plasticity and opioid receptors.
Experimental approaches. To address the contribution of neuro-immune interactions and epigenetics to chronic pain, we combine molecular, biochemistry, immunostaining, pharmacology, genetically modified mice, viral gene therapy, cell transfer and animal behavior in experimental models of chronic pain.
Laumet G, Edralin JD, Chiang ACA, Dantzer R, Heijnen CJ and Kavelaars A. Resolution of inflammation-induced depression requires T lymphocytes and endogenous brain IL-10 signaling. Neuropsychopharmacology. 2018 Dec;43(13):2597-2605.
Garriga J*, Laumet G*, Chen SR, Zhang Y, Madzo J, Pan HL, Issa JP, and Jelinek J. Nerve injury-induced chronic pain is associated with persistent DNA methylation reprogramming in dorsal root ganglion. The Journal of Neuroscience in press (JN-RM-2616-17). * Equal contribution.
Laumet G*, Zhou W*, Dantzer R, Edralin JD, Huo XJ, Budac DP, Mao-Ying QL, O’Connor J, Lee AW, Heijnen CJ and Kavelaars A. Upregulation of Neuronal Kynurenine 3-Monooxygenase (KMO) Mediates Depression-like Behavior in a Mouse Model of Neuropathic Pain. Brain, Behavior, and Immunity 2017 Jul 11. pii: S0889-1591(17)30215-5. * Equal contribution.
Laumet G, Chen SR, Pan HL. NMDA Receptors and Signaling in Chronic Neuropathic Pain. Book chapter, The NMDA receptors, Kenji H (ed), ISBN 978-3-319-49795-2, Springer Nature.
Laumet G. Book Review: Modern Trends in Pharmacopsychiatry Vol. 30 “Pain in Psychiatric Disorders” edited by David P. Fin and Brian E. Leonard, Karger, Basel, Switzerland (2015). Psychoneuroendocrinology. 2016.
Laumet G, Garriga J, Chen SR, Zhang Y, Smith TS, Li DP, Jelinek J, Cesaroni M, Issa JP, and Pan HL. G9a is essential for epigenetic silencing of K+ channel genes and acute-to-chronic transition. Nature Neuroscience 2015 Dec;18(12):1746-55
Zhang Y, Laumet G, Chen SR, Hittelman WN, Pan HL. Pannexin-1 Up-regulation in the Dorsal Root Ganglion Contributes to Neuropathic Pain Development. Journal of BioChemistry 2015 Jun 5;290(23):14647-55