loading
loading
NIH grant 1RF1NS141712-01A1: The role of TRP ion channels in migraine pain
Institute: {'code': 'NS', 'abbreviation': 'NINDS', 'name': 'National Institute of Neurological Disorders and Stroke', 'admin_org_id': '12500053', 'admin_funding_url': ''}. PI: Carlene D Moore. Award: $3833890.
Start: 2026-07-22T00:00:00.
ABSTRACT
Migraine is a highly prevalent and complex neurological disorder that disproportionately affects women
and poses a significant economic burden, with annual treatment costs exceeding $20 billion in the United States
alone. Despite its impact, the precise mechanisms underlying migraine pathophysiology remain incompletely
understood. Our long-term goal is to define the mechanisms that underlie migraine pain, and to provide novel and
effective approaches to reduce its occurrence.
Emerging candidates in migraine research are the Transient Receptor Potential Vanilloid (TRPV) calcium
ion channels, among which TRPV4 is a member. TRPV4 is expressed in key components of the trigeminal sensory
system, including trigeminal (TG) sensory neurons, meningeal mast cells (MCs), and satellite glial cells (SGCs).
TRPV4 plays critical roles in pain perception and neuroinflammation, making it a promising target for investigating
migraine pathophysiology. However, the specific role of TRPV4 in the trigeminal sensory system in the context of
migraines remains a gap in knowledge. MCs and SGCs influence pain sensitivity and TG neuronal excitability,
making them prime candidates for exploring migraine pathophysiology. TRPV4 involvement in pain and migraine,
along with its expression in both MCs and SGCs, further supports its role in migraine-related processes.
The central hypothesis of this proposal is that TRPV4 Ca2+-permeable ion channels in MCs and SGCs
contribute to migraine pain and do so in a sex specific manner. To test this hypothesis, we aim to investigate the
TRPV4 in meningeal MCs as it impacts migraine-related pain and examine the sensitizing impact of TRPV4 in
SGCs on trigeminal sensory neurons. Feasibility for these models and techniques has been established by the
applicants and collaborators. Our innovative approach, which includes TG neuron-MC co-culture techniques, MC
and SGC-specific TRPV4 deletion in mice, in-vivo migraine pain behavioral assessments, in-vivo live animal
monitoring post-migraine induction, and AAV glia-targeted TRPV4 knockdown aims to elucidate the mechanisms
by which TPRV4 in these cell lineage candidates drive migraine and to evaluate the translational relevance to
human migraine pathology. The rationale of this research is that its successful completion will advance our
understanding of how TRPV4-mediated signaling influences the mechanisms underlying migraine
pathophysiology, offering promising avenues for the development of targeted therapeutic interventions to alleviate
the migraine burden and enhance patient outcomes worldwide.document fetched 2026-08-02 08:24