Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain
NINDS - National Institute of Neurological Disorders and Stroke
About This Grant
Project Abstract Neuropathic pain is a common complication of spinal cord injury (SCI), characterized by symptoms of allodynia and hyperalgesia experienced at- and below the level of injury. This type of chronic pain can be spontaneous or evoked, and currently accepted therapeutics display limited efficacy. Neuroimmune interactions are thought to play a central role in the development and maintenance of neuropathic pain. Increased production of proinflammatory mediators after SCI alters the expression of voltage-gated channels on primary nociceptors, driving hypersensitivity and spontaneous activity. This results in aberrant sensory signaling extending from the peripheral dorsal root ganglia (DRG) into the spinal dorsal horn and ascending to supraspinal centers, driving neuropathic pain. Intercellular communications between infiltrating macrophages and neuronal populations in the DRG after injury have drawn considerable interest in the study of neuropathic pain, as these cells have critical contributions to both the development and resolution of chronic pain. Recent work highlights the therapeutic potential of small extracellular vesicles (sEVs) derived from lipopolysaccharide (LPS)-stimulated macrophages in preclinical models of inflammation and pain. Preliminary data from our lab revealed a dramatic resolution of established SCI-induced neuropathic pain and a more normal distribution of nociceptive primary afferents in the spinal cord after intrathecal injection of sEVs released from RAW 264.7 macrophages treated with LPS. However, how sEVs affect nociceptors and/or other cells found along the sensory neuroaxis remains to be established. We hypothesize that sEVs from LPS-stimulated macrophages attenuate aberrant nociceptor plasticity and hyperexcitability to resolve neuropathic pain after SCI via 1: direct internalization by nociceptors in the DRG, or 2: indirectly by affecting endogenous macrophage/microglia mediated mechanisms. Two specific aims have been developed to explore this hypothesis. Our first aim will utilize patch clamp electrophysiology recordings to determine how DRG nociceptors are affected by sEV administration both in vitro and in vivo. The second aim will deplete endogenous macrophages and microglia in hypersensitive SCI rats to determine whether these cells are necessary for the analgesic effect of sEV administration. The data from this proposal will explore how macrophage derived sEVs interact with the neuroimmune environment after SCI in a way that facilitates treatment of neuropathic pain.
Grant Summary
Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain is a NINDS - National Institute of Neurological Disorders and Stroke grant providing up to $50K for university, nonprofit, healthcare org. Applications are due 2028-05-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $50K
2028-05-31
- 1Confirm your organization is eligible for Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain from NINDS - National Institute of Neurological Disorders and Stroke, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NINDS - National Institute of Neurological Disorders and Stroke before the deadline.
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Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain: Frequently Asked Questions
Who is eligible for the Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain?
Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain is offered by NINDS - National Institute of Neurological Disorders and Stroke and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain provide?
Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain provides up to $50K per award from NINDS - National Institute of Neurological Disorders and Stroke. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain deadline?
Applications for Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain are due 2028-05-31 (open). Because deadlines can change, verify the date with the funder, NINDS - National Institute of Neurological Disorders and Stroke, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain?
To apply for Macrophage Derived Small Extracellular Vesicles to Resolve Spinal Cord Injury Induced Pain, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NINDS - National Institute of Neurological Disorders and Stroke.