Download the origin of nociception alteration in rats treated with betacytotoxic

THE ORIGIN OF NOCICEPTION ALTERATION IN RATS TREATED
WITH BETACYTOTOXIC DRUGS; COMPARISON OF HOT PLATE AND
PAW PRESSURE TEST
Melita Šalković-Petrišić, Ivana Ferber and Zdravko Lacković
Department of Pharmacology, Medical School and Croatian Institute for Brain
Research, University of Zagreb, Šalata 11, 10 000 Zagreb, Croatia
Betacytotoxics alloxan and streptozotocin are widely used drugs for induction of
experimental diabetes mellitus in rats following peripheral administration of high
doses, due to their selective toxicity for insulin producing/secreting cells. Diabetes
mellitus is often accompanied by diabetic neuropathy and altered nociception, usually
assumed to be a consequence of the peripheral abnormalities. However, recent
literature data suggest involvement of the central nervous system, as well. Rats treated
intracerebroventricularly (icv) with low doses of betacytotoxic drugs do not get
diabetes mellitus, but develop the state of so called “cerebral diabetes” manifested
with similar brain neurochemistry and cognitive alterations as those seen in diabetes
mellitus. In line with that and the existence of brain insulin system and betacytotoxics
selectivity for insulin producing/secreting cells, betacytotoxic icv – treated rats
present a good experimental model for investigating the central origin of diabetes
related abnormalities. We have investigated the spontaneous pain threshold by means
of two different tests (hot plate and paw pressure test) in rats treated with two
betacytotoxic drugs (alloxan and streptozotocin) following their peripheral,
diabetogenic and central, nondiabetogenic administration. Four weeks following the
drug treatment, the spontaneous pain threshold, determined as a reaction latency time
in the hot plate test was increased in alloxan (+52%)- and streptozotocin (+100%)diabetic rats. Similar, but less pronounced increase was also observed in the hot plate
test in alloxan (+46%) and streptozotocin (+62%) icv-treated rats. However, the
spontaneous pain threshold, determined as a reaction latency time in the paw pressure
test was decreased in alloxan (-45%)- and streptozotocin (-31%)-diabetic animals, as
well as in alloxan (-28%)- and streptozotocin (-23%) icv-treated ones, in comparison
to the respective control animals. Alloxan and streptozotocin have different
mechanisms of action. Therefore, the similarity of the effects they induce, and
moreover, the similarity of their effects after peripheral, diabetogenic and central,
nondiabetogenic administration, suggest that the observed nociception alterations
induced by these drugs are not the consequence of their nonspecific toxic effects.
Furthermore, the presented results support the hypothesis that alloxan- and
streptozotocin-induced alterations of nociception might be of a central origin and not
related to the beta cell destruction. However, it seems that betacytotoxic drugs
differently affect nociception induced by thermal and mechanic noxa, the molecular
mechanism of which remains to be discovered.
Supported by the projects of the Croatian Ministry of Science and Technology
(0108253 and 108134).