Objective
Peripheral sensory neurons drive pain by detecting tissue damage throughout the body, with one notable exception: the brain. Instead, headache pain is thought to originate in the meninges – the protective membranes surrounding the brain, which are densely innervated by sensory neurons from the trigeminal ganglion. However, we still do not fully understand how these neurons are activated during migraine to produce headache pain. Most migraine research has focused on nociceptors that release the neuropeptide calcitonin gene-related peptide (CGRP). Yet the fact not all patients respond to therapies targeting CGRP suggests that additional cellular pathways contribute to migraine. In recent years, molecular profiling has revealed remarkable diversity among sensory neurons, including those that innervate the meninges. Unexpectedly, the meninges also contains neurons, known as NP2 and NP3 cells, that in the skin encode itch. Why these “itch” neurons target an internal tissue, what stimuli they detect, and whether they contribute to migraine pain remains entirely unknown.
In this programme, I will combine molecular genetics, functional imaging, and optogenetic behavioral assays in both male and female mice to define the sensory function of these specialized meningeal neurons. I propose that NP2 and NP3 neurons act as sensors of mast cells, a type of meningeal immune cell previously implicated in migraine. Thus, I will test the hypothesis that mast cells signal to NP2 and NP3 neurons to drive headache pain in migraine. This work challenges the prevailing nociceptor-centric view of migraine pain by postulating a new immunosensory circuit that links mast cell degranulation to the activation of specific meningeal sensory neurons. Ultimately, by revealing how the unique sensory innervation and neuroimmune landscape of the meninges gives rise to headache pain, this work will transform our understanding of migraine mechanisms and uncover new therapeutic targets.
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Keywords
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2026-STG
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WC1E 6BT London
United Kingdom
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