Molecular mechanisms of pain chronification

Chronic neuropathic pain (NP) resulting from peripheral nerve injury can cause prolonged suffering that significantly reduces the quality of life in patients.

Current treatments still consist of repurposed drugs with large spectrum which have poor efficacy on pain alleviation on the long run and have several side effects.

These limitations are clearly associated with a lack of knowledge of the molecular mechanisms and cell types being affected during the transition from acute-to-chronic pain.

Indeed, it is not at all clear what the exact cellular source of spontaneous and hyper-excitability is, whether it originates from nociceptors or non-nociceptor cells. Growing evidence also indicate a role for non-neuronal cells, including macrophages and glial cells.

The goal of this grant is to provide the first comprehensive and integrative map of the epigenomic modifications and transcriptomic changes in the peripheral sensory system, at the single cell level, in different NP models, and together or not with various physical activity regimes to determine the molecular underpinning of preventive and therapeutic trainings onto neuropathic pain pathways.The unique combination of leading-edge techniques such as scRNAseq, scATACseq, scCUT&Tag, among others, will allow us to provide insights into the temporal and cellular regulation of novel mechanisms that might be underlying the effects of peripheral nerve injury on pain sensation and its chronification.