Trace elements represent a group of essential metals or metaloids necessary for life, present in minute amounts. Analgesic adjuvants can enhance the effect of other pain drugs or be used for pain control themselves. Previous studies on the effects of trace elements on nociception and their potential use as analgesic adjuvants have yielded conflicting results. In this study, we tested the hypothesis that three vital trace elements (Zn²⁺, Mg²⁺, Cu²⁺) have direct antinociceptive effects. Groups of eight Swiss mice were intraperitoneally (i.p) injected with incremental concentrations of Zn²⁺ sulfate (0.5, 2.0 mg/kg), Zn²⁺ citrate (0.125, 0.5 mg/kg), Mg²⁺ chloride (37.5, 75, 150 mg/kg), Cu²⁺ chloride (0.5, 1.0, 2.0 mg/kg), and Cu²⁺ sulfate (0.5, 1.0 mg/kg) or saline (control). Evaluations were made by hot plate (HP) and tail flick (TF) tests for central antinociceptive effect, writhing test (WT) for visceral antinociceptive effect, and activity cage (AC) test for spontaneous behavior. Zn²⁺ induced pain inhibition in HP/TF tests (up to 17%) and WT (up to 25%), with no significant differences among the salts used. Mg²⁺ salts induced pain inhibition for all performed tests (up to 85% in WT). Cu²⁺ salts showed antinociceptive effects for HP/TF (up to 28.6%) and WT (57.28%). Only Mg²⁺ and Cu²⁺ salts have displayed significant effects in AC (Mg²⁺ anxiolytic/depressant effect; Cu²⁺ anxiolytic effect). We interpret these data to mean that all tested trace elements induced antinociceptive effects in central and visceral pain tests. Our data indicate the potential use of these cheap adjuvants in pain therapy.
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