Project description
Brain pain control
Modulation of pain varies significantly under the influence of different affective states and occurs through a descending pathway from the brain to the rostral ventromedial medulla (RVM) neurons for execution and projection to the spinal cord. The EU-funded DescendPain project will uncover the ability of the brain to control pain. It will classify RVM neurons and identify neuronal ensembles conferring analgesia and hyperalgesia under different affective states. Activity-based mouse genetics will reveal the engaged neurons and their role in pain modulation. Novel intersectional strategies for active neurons will determine how the descending RVM neurons control pain transmission in the ascending pathway in the spinal cord. The final objective will be the identification of the memory substrate for chronic pain.
Objective
Pain is a large societal and health problem. Although often thought of as an invariant representation of active nociceptors, pain varies a lot under the influence of different affective states, sometimes with near complete analgesia. Such modulation of pain is thought to occur through a descending pathway originating in the brain and to be executed by Rostral Ventromedial Medulla (RVM) neurons that project to the spinal cord. Deciphering the complexity of the cell types involved and how they contribute to the descending control of pain has been challenging, but recent advances in single-cell omics, computational biology and advanced genetic technologies now open for unbiased system-wide insights.
DescendPain will uncover the power of the brain to control pain. We will classify RVM neuron types by single-cell RNA-sequencing and use scRNAseq-based stimulus-to-cell-type mapping to identify neuronal ensembles conferring analgesia and hyperalgesia during morphine, naloxone, stress, sleep-deprivation and exercise. Using activity-based mouse genetics, we will reveal the full complexity of the combinations of neurons engaged and unravel their role in pain modulation, thus identifying for the first time the cellular basis for how affective states modulate pain. We will also use novel intersectional strategies for dual capturing of active neurons to determine how the descending RVM controls the transmission of pain in the ascending pathway of the spinal cord. Finally, we will identify the memory substrate underlying chronic pain, providing evidence for the existence of RVM neuron ensembles of chronic pain and revealing underlying cellular and molecular mechanisms.
This project takes a new system-wide strategy in the pain field that should fundamentally change the view of pain, by providing a cellular basis for how it is continuously scaled by mental states and uncovering mechanisms of chronic pain, which may provide strategies for designing effective pain therapies.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
171 77 STOCKHOLM
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.