Preclinical toxicity screening of intrathecal oxytocin in rats and dogs.
Background: Anatomic, physiologic, and behavioral studies in animals suggest that spinally released oxytocin should produce analgesia in humans and may also protect from chronic pain after injury. In this article, the authors report preclinical toxicity screening of oxytocin for intrathecal delivery...
| Publicado en: | Anesthesiology Vol. 120; no. 4; pp. 951 - 962 |
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| Autores principales: | , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
2014 Apr
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=107898658&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 107898658 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00033022 1V8 jtl: Anesthesiology issn: 00033022 maglogo: N pubinfo: dt: 2014 Apr vid: 120 iid: 4 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 107898658 107898658 NLM24492326 2012534284 10.1097/ALN.0000000000000148 NLM24492326 107898658 ppf: 951 ppct: 11 formats: tig: atl: Preclinical toxicity screening of intrathecal oxytocin in rats and dogs. aug: au: Yaksh, Tony L Hobo, Shotaro Peters, Christopher Osborn, Kent G Richter Jr, Philip J Rossi, Steven S Grafe, Marjorie R Eisenach, James C Richter, Philip J Jr affil: From the Department of Anesthesiology, University of California, San Diego, San Diego, California (T.L.Y.); Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.H., C.P., and J.C.E.); Diagnostic Laboratory, Animal Care Program, University of California, San Diego, San Diego, California (K.G.O.); Animal Care Program, Department of Pathology, University of California, San Diego, San Diego, California (P.J.R.); Anesthesiology Research Laboratory, University of California, San Diego, San Diego, California (S.S.R.); and Department of Pathology, Neuropathology Oregon Health Sciences University, Portland, Oregon (M.R.G.). sug: subj: Oxytocics Oxytocin Animal Studies Behavior, Animal Drug Effects Blood Pressure Drug Effects Dogs Dose-Response Relationship, Drug Drug Administration Schedule Drug Evaluation, Preclinical Female Heart Rate Drug Effects Injections, Intraspinal Male Oxytocics Administration and Dosage Oxytocin Administration and Dosage Prospective Studies Pruritus Chemically Induced Random Assignment Rats Toxicity Tests Female Male ab: Background: Anatomic, physiologic, and behavioral studies in animals suggest that spinally released oxytocin should produce analgesia in humans and may also protect from chronic pain after injury. In this article, the authors report preclinical toxicity screening of oxytocin for intrathecal delivery.Methods: Intrathecal oxytocin, 11 μg (6 U) or vehicle, was injected intrathecally in 24 rats, followed by frequent behavioral assessment and histologic examination of spinal contents 2 or 14 days after injection. In three dogs, a range of intrathecal oxytocin doses (18 to 550 μg in 0.5 ml) was injected followed by physiologic, biochemical, and behavioral assessments. Ten dogs were then randomized to receive five daily injections of intrathecal oxytocin, 550 μg in 0.5 ml, or vehicle with similar assessments and, necropsy and histologic analysis were conducted 2 days later.Results: In rats, intrathecal oxytocin resulted in transient scratching and itching behaviors, without other differences from vehicle. There was no behavioral, gross anatomic, or histologic evidence of neurotoxicity. Dose ranging in dogs suggested mild effects on motor tone, blood pressure, and heart rate at the 550 μg dose. Repeated boluses in dogs did not produce behavioral, biochemical, neurological, gross anatomic, or histologic evidence of neurotoxicity.Conclusions: Substances, including natural neurotransmitters, may be toxic when administered in pharmacologic doses in the spinal cord. This preclinical toxicity screen in two species suggests that bolus injections of oxytocin in concentrations up to 1,100 μg/ml are unlikely to cause neurotoxicity. The authors also support cautious clinical application of intrathecal oxytocin under regulatory supervision. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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