Influence of cadmium intoxication on rats' pain sensitivity before and after blocking D₂-, 5HT₃- and AT₁-receptors

During our experiments, the rats’ pain thresholds were determined against a background of cadmium chloride intoxication before and after blocking D2-, 5HT3- and AT1-receptors. We studied eight groups (10 animals in each group) of albino male rats weighing 230-240 g with an average locomotive activity. During seven days, four groups obtained CdCl2 (1 mg/kg) and saline was injected to four other groups of rats. Later, for three days, two groups (one with and another without intoxication) received injection of one of the antagonists: D2-receptors, haloperidol 2.5 mg/kg or 5HT3-receptors, osetron 2 mg/kg or AT1-receptor kandesar 0.2 mg/kg. One group was the control group, that received only saline. We gave each injection once a day intraperitoneally in a volume of 0.2 ml. On the tenth day an hour after appropriate injection the indicators of pain sensitivity were determined in rats in two tests: the “hot plate” (latent period of pain reaction - LP); and “electrical stimulation” (the pain threshold - PT). The significance of differences between parameters was determined by criterion of Mann-Whitney (U-test). Statistical procedures were performed with the help of StatSoft STATISTICA 6.0, and charting was made in EXEL. We did not identify LP changes after chronic accumulation of cadmium chloride in animals, but PT increased by 138%, so cadmium chloride influenced the formation of pain sensitivity only by electrical stimuli. It is known that in the case of a substance ability to pass the blood brain barrier test, “hot plate” reflects the peculiarities of their influence on supraspinal (SSp), and the test “electrical stimulation” - the SSp and spinal (Sp) levels. The absence of changes of LP parameter and increased PT after cadmium chloride intoxication indicated the action of cadmium on pain sensitivity mainly on Sp level. After blocking D2-receptor in unintoxicated rats LP increased by 227% and PT by 200%, i.e. D2-receptors on SSp and Sp levels were involved in the formation of pain sensitivity. The level of LP increased by 225% and PT by up to 133% in rats intoxicated by cadmium chloride after blocking D2-receptors against control. But comparing against parameters of intoxicated rats, significant differences of LP and BP were not detected; therefore there is a nonsignificant role of the D2-receptors in the formation of pain sensitivity. After blocking the 5HT3-receptors and AT1-receptors, no significant changes of LP were detected, but there was an increase in PT by up to 137% and 168%, respectively. Obviously, 5HT3- and AT1-receptors regulate pain sensitivity on Sp level. The cadmium chloride did not change the role of these receptors in the formation of pain sensitivity. Comparative analysis of the effects of blockers before and after intoxication of cadmium chloride in rats showed that against a background of cadmium chloride intoxication, the effect of antagonist D2-receptor was different, and the effects of antagonists 5HT3-and AT1- receptors did not change. According to the data in the literature, the main reason for the changes of the antagonist’s effects is impaired functioning of the neurotransmitter systems. Our results demonstrate that the dopamine system is the most sensitive system to the presence of cadmium in the body. The article contains 3 figures, 1 table, 23 ref.

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