ArticleAnesthesiology2013
Intrathecal substance P-saporin in the dog: distribution, safety, and spinal neurokinin-1 receptor ablation.
Article in Anesthesiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
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- Pain Treatment in the Companion Canine Model to Validate Rodent Results and Incentivize the Transition to Human Clinical Trials.Frontiers in pharmacology · 2021Review
- Detection of neurokinin-1 receptor by immunohistochemistry in canine mammary gland tumours.Veterinary medicine and science · 2020Article
- Frontiers in Pain Research: A Scope of Its Focus and Content.Frontiers in pain research (Lausanne, Switzerland) · 2020Article
- The Establishment of a CSF-Contacting Nucleus "Knockout" Model Animal.Frontiers in neuroanatomy · 2018Article
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- Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics.Anesthesia and analgesia · 2017Review
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- Current and Future Issues in the Development of Spinal Agents for the Management of Pain.Current neuropharmacology · 2017Review
- Current status and future directions of botulinum neurotoxins for targeting pain processing.Toxins · 2015Review
- High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs.Gene therapy · 2015Article
- The search for novel analgesics: targets and mechanisms.F1000prime reports · 2015Review
- Substance P-saporin for bone cancer pain in dogs: can man's best friend solve the lost in translation problem in analgesic development?Anesthesiology · 2013Article
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- Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular.International journal of toxicologyArticle
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13 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundNeurokinin-1 receptors (NK1-rs) located on superficial dorsal horn neurons are essential for integration of nociceptive input. Intrathecal injection of substance P-saporin (SP-SAP) leads to local loss of spinal NK1-r (+) neurons suggesting its potential as a therapeutic agent for chronic pain. The authors determined, in a canine model, effects of lumbar intrathecal SP-SAP.
methodsDistribution of SP-SAP and Saporin was determined in plasma, lumbar cerebrospinal fluid, and tissue. Safety of intrathecal SP-SAP was determined in four groups (six dogs each) administered 0 (0.9% saline), 1.5, 15, or 150 µg SP-SAP through lumbar intrathecal catheters. Behavioral, physiologic, and biochemical variables were assessed. Spinal tissues were collected at 7 and approximately 90 days, or earlier if significant morbidity developed, and analyzed for NK1-r (+) neuron loss and histopathology.
resultsSP-SAP and Saporin were detectable in lumbar cerebrospinal fluid for up to 4 and 24 h, respectively. Animals receiving intrathecal saline, 1.5, or 15 µg of SP-SAP showed no persistent neurologic deficits. Three animals receiving 150 µg of SP-SAP developed pelvic limb paraparesis and were euthanized prematurely. Immunohistochemistry and in situ hybridization cell counts confirmed a significant reduction in NK1-r (+) in superficial dorsal horn neurons from lumbar spinal cord after intrathecal administration of 15 and 150 µg of SP-SAP. A significant loss of NK1-r neurons in the lumbar ventral horn occurred only with 150-µg SP-SAP.
conclusionIntrathecal 15-µg SP-SAP reduced dorsal, but not ventral, NK1-r (+) neurons at the spinal level of delivery with minimal side effects, whereas 150-µg SP-SAP resulted in motor neuron toxicity.
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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.