Document Detail


Neonatal administration of a vaccine preservative, thimerosal, produces lasting impairment of nociception and apparent activation of opioid system in rats.
MedLine Citation:
PMID:  19747466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mieszko Olczak; Michalina Duszczyk; Pawel Mierzejewski; Maria Dorota Majewska
Related Documents :
14642786 - Effect of drugs active at adenosine receptors upon chronic stress-induced hyperalgesia ...
15752576 - Antinociceptive and antipyretic effects of a derivatized tetrapeptide from lactoferrin ...
7832306 - The addition of 7.5% glucose does not alter the neurotoxicity of 5% lidocaine administe...
1407686 - Intrathecal midazolam versus intrathecal morphine in orofacial nociception: an experime...
20345766 - Pre-synaptic glutamate-induced activation of da release in the striatum after partial n...
18024786 - Characterization of the novel p-selectin inhibitor psi-697 [2-(4-chlorobenzyl)-3-hydrox...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-09
Journal Detail:
Title:  Brain research     Volume:  1301     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-06     Completed Date:  2010-01-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  143-51     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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


Previous Document:  The ventrolateral upper cervical cell group in cat projects to all rostrocaudal levels of the periaq...
Next Document:  Exposure to nitrous oxide stimulates a nitric oxide-dependent neuronal release of beta-endorphin in ...