ArticleMolecular pain
Therapeutic potential of Pak1 inhibition for pain associated with cutaneous burn injury.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- RAGE mediates LPS-induced inflammatory pain in human skin - a double-blind, randomised, placebo-controlled full crossover study.Nature communications · 2026Trial
- PAK1 inhibitor NVS-PAK1-1 preserves dendritic spines in amyloid/tau exposed neurons and 5xFAD mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The impact of burn injury on the central nervous system.Burns & trauma · 2024Review
- Electroacupuncture inhibits dendritic spine remodeling through the srGAP3-Rac1 signaling pathway in rats with SNL.Biological research · 2023Article
- Human Immunodeficiency Virus Persistence in the Spleen: Opportunities for Pharmacologic Intervention.AIDS research and human retroviruses · 2021Article
- Conditional RAC1 knockout in motor neurons restores H-reflex rate-dependent depression after spinal cord injury.Scientific reports · 2021Article
- Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021Review
- Sculpting Dendritic Spines during Initiation and Maintenance of Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Review
- Dendritic Spine Dynamics after Peripheral Nerve Injury: An Intravital Structural Study.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Spinal cord motor neuron plasticity accompanies second-degree burn injury and chronic pain.Physiological reports · 2019Article
- Rac1/PAK1 signaling contributes to bone cancer pain by Regulation dendritic spine remodeling in rats.Molecular painArticle
- Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Painful burn injuries are among the most debilitating form of trauma, globally ranking in the top 15 leading causes of chronic disease burden. Despite its prevalence, however, chronic pain after burn injury is under-studied. We previously demonstrated the contribution of the Rac1-signaling pathway in several models of neuropathic pain, including burn injury. However, Rac1 belongs to a class of GTPases with low therapeutic utility due to their complex intracellular dynamics. To further understand the mechanistic underpinnings of burn-induced neuropathic pain, we performed a longitudinal study to address the hypothesis that inhibition of the downstream effector of Rac1, Pak1, will improve pain outcome following a second-degree burn injury. Substantial evidence has identified Pak1 as promising a clinical target in cognitive dysfunction and is required for dendritic spine dysgenesis associated with many neurological diseases. In our burn injury model, mice exhibited significant tactile allodynia and heat hyperalgesia and dendritic spine dysgenesis in the dorsal horn. Activity-dependent expression of c-fos also increased in dorsal horn neurons, an indicator of elevated central nociceptive activity. To inhibit Pak1, we repurposed an FDA-approved inhibitor, romidepsin. Treatment with romidepsin decreased dendritic spine dysgenesis, reduced c-fos expression, and rescued pain thresholds. Drug discontinuation resulted in a relapse of cellular correlates of pain and in lower pain thresholds in behavioral tests. Taken together, our findings identify Pak1 signaling as a potential molecular target for therapeutic intervention in traumatic burn-induced neuropathic pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.