Subject: Role and regulation of ASIC channels in pain processes at the spinal cord level
Summary: ASICs (Acid-Sensing Ion Channels) are a family of excitatory ion channels (ASIC1 to ASIC3) widely expressed throughout the pain neuraxis. These channels are sensors of extracellular acidity and are activated by protons. Different subtypes of ASIC channels have been characterized in peripheral sensory neurons and nociceptors, the dorsal horn of the spinal cord or the brain. We have recently identified, in patients, endogenous lipids (Jacquot et al., 2021; Marra & Deval, 2016; Marra et al., 2016) capable of strongly modulating ASIC3 channel activity in the periphery, and of generating a chronic pain state in a preclinical model of joint pain (Jacquot et al., 2021). In this model, we were able to demonstrate a sensitization of spinal neurons and anxiety- pain comorbidity phenomena. This thesis project will study the role of central ASIC channels (mainly ASIC1 and ASIC2) in the mechanisms of central sensitization and anxiety-pain comorbidity associated with chronic pain states. Several approaches will be used, including electrophysiology, behavioral studies and localization experiments (RNAscope), in combination with pharmacological and genetic tools.
Financial support: This PhD thesis will be funded by the LabEx ICST and it will start on October 2021.