Editor’s note: This is the 17th in a series of weekly PRF seminars to help keep the pain research community connected during the COVID-19 pandemic and to provide all members of our community with virtual educational opportunities. The seminar series is supported by the Center for Advanced Pain Studies at the University of Texas at Dallas, US, and this particular seminar is also supported by Cellectricon. We thank both for their generous support.
On August 31, 2020, the IASP Pain Research Forum hosted a seminar with Thiago Cunha, PhD, University of São Paolo, Brazil. A Q&A session moderated by Marzia Malcangio, PhD, King's College London, UK, followed the presentation.
A recording of this webinar will soon be freely available to IASP members at the IASP Pain Education Resource Center (PERC).
Here is an abstract from Dr. Cunha:
Neuropathic pain, which is triggered by damage or disease of the somatosensory system, is one of the most important types of chronic pain. Nevertheless, critical pathophysiological mechanisms that maintain neuropathic pain are poorly understood. In this talk, I will show that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) is ablated pharmacologically or genetically. Mechanistically, an upregulation of indoleamine 2,3-dioxigenase in dendritic cells that accumulate in the dorsal root leptomeninges leads to an increase in levels of kynurenine (Kyn) in the spinal cord. In the spinal cord, Kyn is metabolized by astrocyte-expressed kynurenine-3-monooxygenase into a pro-nociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase-derived quinolinic acid, the final step of the canonical KYNPATH, is also involved in neuropathic pain development through the activation of glutamatergic NMDA receptors. In conclusion, these data reveal a previously undetermined role for KYNPATH as an important neuroimmune-glia communication mechanism involved in the maintenance of neuropathic pain. This novel paradigm offers potential new targets for drug development against this type of chronic pain.
About the presenter
Thiago Cunha, PhD, received his PhD in pharmacology at the University of São Paulo under the supervision of Prof. Sergio Ferreira. Currently, he is an Associate Professor in the same department. He did a sabbatical period in the Department of Immunology at Harvard Medical School. His lab is mainly focused on the neurobiology of chronic pain, especially the mechanisms by which immune and glial cells participate in this process. He received the 2020 Patrick D. Wall Young Investigator Award for Basic Science, a prestigious award given by the International Association for the Study of Pain (IASP).
About the moderator
Marzia Malcangio PhD, is professor of neuropharmacology at King’s College London, UK. Her research is devoted to the study of the positive and negative modulation of pain transmission, with an emphasis on chronic pain. Her research group is currently focusing on neuro-immune interactions in settings of chronic pain, covering a range of specific pain subtypes from neuropathic pain to cancer-induced bone pain. To date, she has published over 100 papers on pain and edited a book on synaptic plasticity in pain. In doing so, she has explained fundamental mechanisms and identified new targets in chronic pain, including protease and chemokine pathways in microglia and macrophage-mediated mechanisms. She also leads the Wolfson CARD, which groups together researchers whose work seeks to advance our understanding of sensory systems including pain, deafness, and nervous system injury, repair and regeneration.
Join the conversation about the seminar on Twitter @PainResForum #PRFSeminar
We thank the Center for Advanced Pain Studies at the University of Texas at Dallas, US, and Cellectricon, Mölndal, Sweden, for their support of this seminar.
