Editors' note: The October 30 webinar with speaker Michael Salter is now available for viewing. Access the presentation and panel discussion below.
Neuron-glia interactions are increasingly recognized as being key for physiological and pathological processes in the central nervous system. Microglia have been found to play a causal role in neuropathic pain behaviors resulting from peripheral nerve injury, and a core neuron-microglia-neuron signaling pathway has been elucidated. In an October 30 webinar, presenter Michael Salter, of the Hospital for Sick Children and the University of Toronto, Canada, discussed findings from his lab and others on neuron-glia crosstalk in pain, and how that activity might be targeted for pain therapy.
Within the dorsal horn, microglia suppress neuronal inhibition by a cascade involving activation of microglial P2X4 receptors, causing the release of brain-derived neurotrophic factor (BDNF). BDNF acts on trkB receptors, which leads to a rise in intracellular chloride concentration in dorsal horn nociceptive output neurons, transforming the response properties of these neurons. In addition to suppressing inhibition, peripheral nerve injury causes activity-dependent facilitation at dorsal horn glutamatergic synapses, which enhances nociceptive transmission. This enhancement is mediated by intracellular signaling networks involving serine/threonine and tyrosine kinases within nociceptive transmission neurons. Key for this enhancement is facilitation of NMDA receptor function by Src family tyrosine kinases. Microglia-to-neuron signaling is critical not only for pain hypersensitivity after peripheral nerve injury but also for the paradoxical hyperalgesic effect of morphine and other opioids. Salter and his colleagues anticipate that by targeting microglia-neuron signaling pathways, new therapeutic strategies for chronic pain as well as its comorbid sequelae may be developed.
Following the presentation, a distinguished panel discussed important issues raised by Salter's presentation. The discussion featured:
- Iain Chessell, MedImmune, Cambridge, UK
- Philippe Séguéla, McGill University, Montreal, Canada
- Marzia Malcangio, King’s College London, UK (moderator)
A recording of the webinar is available below.
Listen to the webinar.
Exploring Neuron-Glia Crosstalk in Pain is the fourth in a series of PRF webinars supported by the Mayday Fund. See previous PRF webinars.