ArticlePain2017
Therapeutic potential for leukocyte elastase in chronic pain states harboring a neuropathic component.
Article in Pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed.
- The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study.Diabetes & vascular disease researchTrial
- Post-Herpetic Neuralgia: Review of Pathophysiology, Mechanisms, and Drug Treatment.Current neuropharmacology · 2026Review
- Efficacy and safety of sivelestat sodium hydrate adjunct to remifentanil for analgesia in patients under mechanical ventilation (SIDING trial): protocol of a multicenter, randomized, double-blinded, placebo-controlled trial.Frontiers in medicine · 2026Article
- β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury.NeuroSci · 2025Article
- Steroid inhibited Serpina3n expression which was positively correlated with the degrees of spinal cord injury.Heliyon · 2024Article
- The dorsal root ganglion as a target for neurorestoration in neuropathic pain.Neural regeneration research · 2024Review
- Unraveling impact and potential mechanisms of baseline pain on efficacy of immunotherapy in lung cancer patients: a retrospective and bioinformatic analysis.Frontiers in immunology · 2024Article
- Immunotherapies in chronic pain through modulation of neuroimmune interactions.Pharmacology & therapeutics · 2023Review
- Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from theInternational journal of molecular sciences · 2023Article
- Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The role of neuroinflammation in the transition of acute to chronic pain and the opioid-induced hyperalgesia and tolerance.Frontiers in pharmacology · 2023Review
- Review
- Potential Neuroimmune Interaction in Chronic Pain: A Review on Immune Cells in Peripheral and Central Sensitization.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Sulfonated Nonsaccharide Heparin Mimetics Are Potent and Noncompetitive Inhibitors of Human Neutrophil Elastase.ACS omega · 2021Article
- Neuro-Immunity and Gut Dysbiosis Drive Parkinson's Disease-Induced Pain.Frontiers in immunology · 2021Review
- Ulinastatin Exhibits Antinociception in Rat Models of Acute Somatic and Visceral Pain Through Inhibiting the Local and Central Inflammation.Journal of pain research · 2021Article
- Sex differences in neuro(auto)immunity and chronic sciatic nerve pain.Biology of sex differences · 2020Review
- Novel Analgesics with Peripheral Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- MHCII-restricted T helper cells: an emerging trigger for chronic tactile allodynia after nerve injuries.Journal of neuroinflammation · 2020Review
- Cytotoxic Immunity in Peripheral Nerve Injury and Pain.Frontiers in neuroscience · 2020Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropathic pain is an integral component of several chronic pain conditions and poses a major health problem worldwide. Despite emerging understanding of mechanisms behind neuropathic pain, the available treatment options are still limited in efficacy or associated with side effects, therefore making it necessary to find viable alternatives. In a genetic screen, we recently identified SerpinA3N, a serine protease inhibitor secreted in response to nerve damage by the dorsal root ganglion neurons and we showed that SerpinA3N acts against induction of neuropathic pain by inhibiting the T-cell- and neutrophil-derived protease, leucocyte elastase (LE). In the current study, via detailed in vivo pharmacology combined with analyses of evoked- and spontaneous pain-related behaviors in mice, we report that on systemic delivery, a single dose of 3 independent LE inhibitors can block established nociceptive hypersensitivity in early and late phases in the spared nerve injury model of traumatic neuropathic pain in mice. We further report the strong efficacy of systemic LE inhibitors in reversing ongoing pain in 2 other clinically relevant mouse models-painful diabetic neuropathy and cancer pain. Detailed immunohistochemical analyses on the peripheral tissue samples revealed that both T-Lymphocytes and neutrophils are the sources of LE on peripheral nerve injury, whereas neutrophils are the primary source of LE in diabetic neuropathic conditions. In summary, our results provide compelling evidence for a strong therapeutic potential of generic LE inhibitors for the treatment of neuropathic pain and other chronic pain conditions harboring a neuropathic pain component.
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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.