| Neonatal administration of a vaccine preservative, thimerosal, produces lasting impairment of nociception and apparent activation of opioid system in rats. | |
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MedLine Citation:
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PMID: 19747466 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thimerosal (THIM), an organomercury preservative added to many child vaccines is a suspected factor in pathogenesis of neurodevelopmental disorders. We examined the pharmacokinetics of Hg in the brain, liver and kidneys after i.m. THIM injection in suckling rats and we tested THIM effect on nociception. THIM solutions were injected to Wistar and Lewis rats in a vaccination-like mode on PN days 7, 9, 11 and 15 in four equal doses. For Wistar rats these were: 12, 48, 240, 720, 1440, 2160, 3000 microg Hg/kg and for Lewis: 54, 216, 540 and 1080 microg Hg/kg. Pharmacokinetic analysis revealed that Hg from THIM injections accumulates in the rat brain in significant amounts and remains there longer than 30 days after the injection. At the 6th week of age animals were examined for pain sensitivity using the hot plate test. THIM treated rats of both strains and sexes manifested statistically significantly elevated pain threshold (latency for paw licking, jumping) on a hot plate (56 degrees C). Wistar rats were more sensitive to this effect than Lewis rats. Protracted THIM-induced hypoalgesia was reversed by naloxone (5 mg/kg, i.p.) injected before the hot plate test, indicative of involvement of endogenous opioids. This was confirmed by augmented catalepsy after morphine (2.5 mg/kg, s.c.) injection. Acute THIM injection to 6-week-old rats also produced hypoalgesia, but this effect was transient and was gone within 14 days. Present findings show that THIM administration to suckling or adult rats impairs sensitivity to pain, apparently due to activation the endogenous opioid system. |
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Authors:
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Mieszko Olczak; Michalina Duszczyk; Pawel Mierzejewski; Maria Dorota Majewska |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-09 |
Journal Detail:
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Title: Brain research Volume: 1301 ISSN: 1872-6240 ISO Abbreviation: Brain Res. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-06 Completed Date: 2010-01-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 143-51 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Animals, Newborn Brain Chemistry Catalepsy / chemically induced Dose-Response Relationship, Drug Kidney / chemistry Liver / chemistry Mercury / analysis* Morphine / pharmacology Naloxone / pharmacology Narcotic Antagonists / pharmacology Narcotics / pharmacology Pain Measurement / drug effects Pain Threshold / drug effects* Preservatives, Pharmaceutical / administration & dosage Rats Rats, Wistar Receptors, Opioid, mu / metabolism* Species Specificity Thimerosal / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/Narcotic Antagonists; 0/Narcotics; 0/Preservatives, Pharmaceutical; 0/Receptors, Opioid, mu; 465-65-6/Naloxone; 54-64-8/Thimerosal; 57-27-2/Morphine; 7439-97-6/Mercury |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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