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Multimodal functional neuroimaging techniques to probe the representation of pain in the human brain

Final Report Summary - PROBING-PAIN (Multimodal functional neuroimaging techniques to probe the representation of pain in the human brain)

The ability to perceive pain is crucial for survival, as exemplified by the injuries and reduced life expectancy of people with congenital insensitivity to pain. Furthermore, pain is a major healthcare issue and its treatment, especially in the context of pathological chronic pain, constitutes a very problematic challenge for physicians. Because of its aversive quality and its high prevalence, chronic pain affects the quality of life of millions of individuals and imposes a severe financial burden upon our societies. Yet, how the perception of pain emerges from human brain activity remains a largely unresolved enigma. Crucially, the nociceptive system, conducting noxious sensory input from the periphery to the brain, is not a static hardwired system. Following injury, inflammation or sustained noxious input, plastic changes in nociceptive pathways take place at both peripheral and central levels. These changes lead to sensitization and are thought to contribute largely to the establishment and maintenance of chronic pain.

In this project, we developed new methods to study non-invasively how pain is represented in the human brain, and how changes in brain function may lead to the development of chronic pain. A first approach consisted in using a novel “frequency tagging” technique to mark brain activity specifically related to the perception of sustained experimental pain in the human electroencephalogram. A second approach consisted in combining electroencephalography or functional magnetic resonance imaging with transcranial magnetic stimulation, transcranial direct current stimulation or transcranial focused ultrasounds to measure directly the changes in brain connectivity and excitability related to the development of chronic pain. A third approach consisted in recording pain-related neural activity directly within the human insula in patients implanted with depth electrodes for the diagnostic work-up of partial intractable epilepsy.

In addition to providing a better understanding of how pain emerges from brain activity, the project has generated a set of new tools that can be used for future research, some of which create important clinical perspectives. For example, PROBING-PAIN contributed to the development of a human biomarker of the central sensitization of the pain system that could be used in future projects to accelerate the development of novel analgesics, or to predict response to treatment.