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.
The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.
Background and Aims. Risk score questionnaires for the screening of type 2 diabetes mellitus (DM) present high accuracy, especially the Finnish Diabetes Risk Score (FINDRISC IMT (r=0.24, p=0.01), PWV (r=0.26, p=0.008) or LVMI (r=0.23, p=0.01)
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