Neonatal administration of a vaccine preservative, thimerosal, produces lasting impairment of nociception and apparent activation of opioid system in rats.
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.
Olczak
Mieszko
M
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Duszczyk
Michalina
M
Mierzejewski
Pawel
P
Majewska
Maria Dorota
MD
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry; D002375:Catalepsy / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008628:Mercury / Q000032:analysis*; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013045:Species Specificity; D013849:Thimerosal / Q000008:administration & dosage*
D009292:Narcotic Antagonists; D009294:Narcotics; D011310:Preservatives, Pharmaceutical; D017450:Receptors, Opioid, mu; D013849:Thimerosal; D009270:Naloxone; D009020:Morphine; D008628:Mercury