Team Emmanuel BOURINET

Chronic pain, with a prevalence of 20-30%, is the world’s leading cause of human suffering. Current treatments for this pathological pain remain limited. To better understand neuronal pain pathways and their pathological dysfunction, our team is exploring the impact of ion channels regulating calcium entry into cells. These channels are essential proteins for the initiation, propagation and transmission of information from neuron to neuron. We aim to understand the impact of calcium channels in pain pathophysiology by focusing on peripheral sensory neurons and spinal circuits using mouse genetics, electrophysiology, pharmacology, biochemistry and behavior in preclinical models of chronic pain. Moreover, the presence of the Cav3.2 channel at the heart of our projects in subtypes of sensory neurons dedicated to the perception of mechanical stimuli integrates our work into the elucidation of the molecular mechanisms of the sense of touch beyond the pain theme. We are convinced that preclinical results need to be validated in human tissues to reinforce their credibility in clinical perspectives. In collaboration with the Montpellier Hospital, we are therefore developing ex vivo molecular and functional explorations in sensory neurons and human spinal cord taken from organ donors. At the same time, we are studying autoimmune disorders of peripheral nervous system neurons to understand the mechanism of action of patients’ autoantibodies. Thus, we are positioning our research on a translational strategy prioritizing molecular pathways conserved between animal models and humans to maximize our chances of uncovering the mechanisms of pain pathophysiology.

Axis 1
The questions addressed around the role of low-threshold calcium channels concern:
1) their impact on cutaneous and visceral mechanoreceptive sensory neurons
2) their role in spinal neural networks for the integration of sensory information
3) their participation in the excitability of supraspinal circuits activated by mechanoreceptors.
These questions are addressed using preclinical pain models close to the clinic, and using human tissue to validate preclinical work.

Axis 2
In parallel, we are studying autoimmune disorders of peripheral neurons, focusing on demyelinating nodopathies. This approach is directly integrated into the clinic by characterizing sera from patients suffering from these painful pathologies.