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Comparable antinociceptive effect of biphalin in mice selected for high and low swim stress-induced analgesia after blood-brain barrier disruption caused by hyperosmolar mannitol administration

Anna Klinowiecka 1Piotr Kosson 1Anna A. Leśniak 1Mariusz Sacharczuk 2Bogdan Sadowski 2Andrzej W. Lipkowski 1

1. Polska Akademia Nauk, Instytut Medycyny Doświadczalnej i Klinicznej (PAN), Warszawa, Poland
2. Institute of Genetics and Animal Breeding, ul. Postępu 5, Jastrzębiec 05-552, Poland

Abstract

Bidirectional selection of Swiss-Webster mice for high (HA) and low (LA) swim stress-induced analgesia caused substantial differences in endogenous pain inhibition mechanisms triggered by stress. In the HA line endogenous opioid peptides secreted during stress as well as exogenously administered opioid peptides cause considerable analgesia as opposed to the LA line. The mechanism of increased analgesia in HA mice resulting from exposure to stress is still unclear and demanded investigation. A hypothesis has been put forward that these lines differ in blood-brain barrier permeability, hence differences in analgesic potency of exogenous alkaloid and opioid peptides. Moreover, ultramicroscopic studies displayed pathological changes in morphology of BBB in HA and LA mice.  In our study we observed a differential response of HA and LA mice to a systemic administration of a dimeric enkephalin analog-biphalin. This study aimed to evaluate whether the analgesic potency of biphalin would alter after blood-brain barrier disruption caused by hyperosmolar mannitol. Intravenous administration of mannitol (20%) before biphalin (10 mg/kg) produced comparable antinociceptive effects in tail flick and hot plate tests in HA and LA mice. In LA mice pretreated with mannitol hot plate and tail-flick latencies were noticeably higher than in saline pretreated mice, whereas in HA mice the effect of mannitol pretreatment was very small. Our study suggests that changes in blond-brain barrier permeability are one of the major factors resulting from selection for high and low stress-induced analgesia.

 

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See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-18 13:08
Revised:   2010-03-25 14:00