Pharmacol Rep
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This study was aimed at determining the analgesic effect of gabapentin and tiagabine, two antiepileptic drugs that were administered alone and in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice. Linear regression analysis was used to evaluate the dose-response relationships between logarithms of antiepileptic drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, we calculated doses that increased the antinociceptive effect by 50% (ED(50) values) for gabapentin, tiagabine and their combination. ⋯ With isobolography, the experimentally derived ED(50 mix) value for the fixed ratio combination of 1:1 was 139.31 mg/kg and significantly differed from the theoretically calculated ED(50 add) value, which was 255.04 mg/kg (p < 0.05), indicating the synergistic interaction between gabapentin and tiagabine in the hot-plate test in mice. In conclusion, the combination of tiagabine with gabapentin at a fixed ratio of 1:1 exerted a synergistic interaction in the mouse model of nociceptive pain. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial for pain relief in humans.
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The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. ⋯ Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized "ROS and iron" hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.
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This study was aimed at determining the analgesic effects of vigabatrin (VGB, a newer antiepileptic drug) in the acute thermal pain model (hot-plate test) in mice. Linear regression analysis was used to evaluate a dose-response relationship between logarithms of VGB doses and their resultant maximum possible antinociceptive effects (MPAE) in the hot-plate test in mice. ⋯ In conclusion, VGB in a dose-dependent manner produces the analgesic effects in mice in the hot-plate test. The method allowing for the calculation of doses of VGB increasing the antinociceptive effects by 15%, 20% and 25% can be readily adapted to preclinical studies because these values perfectly characterize the potency of antiepileptic drugs with respect to suppression of acute thermal pain in mice.
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Randomized Controlled Trial Comparative Study
Comparison of the analgesic efficacy of preemptive and preventive tramadol after lumpectomy.
The aim of this study was to investigate the analgesic efficacy of tramadol administrated preemptively or preventively in the earlier period of lumpectomy. Four hundred American Society of Anesthesiologists (ASA) physical status I-II patients, undergoing lumpectomy, were screened and 317 were randomly assigned into one of two groups. In the preemptive tramadol (n = 158) group, patients received an iv injection of tramadol 100 mg 15 min before operation. ⋯ In conclusion, preemptive and preventive administration of tramadol expressed analgesia of similar efficacy up to 24 h after lumpectomy. The additional morphine requirement, the overall satisfaction and the frequency of side effects all did not display significant difference between the two groups. This implies that the administration of tramadol either before the start or before the end of the surgical procedures all can produce effective postoperative analgesia.
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Review
Modulation of microglia can attenuate neuropathic pain symptoms and enhance morphine effectiveness.
Microglia play a crucial role in the maintenance of neuronal homeostasis in the central nervous system, and microglia production of immune factors is believed to play an important role in nociceptive transmission. There is increasing evidence that uncontrolled activation of microglial cells under neuropathic pain conditions induces the release of proinflammatory cytokines (interleukin - IL-1beta, IL-6, tumor necrosis factor - TNF-alpha), complement components (C1q, C3, C4, C5, C5a) and other substances that facilitate pain transmission. Additionally, microglia activation can lead to altered activity of opioid systems and neuropathic pain is characterized by resistance to morphine. ⋯ IL-10 is very interesting since it reduces allodynia and hyperalgesia by suppressing the production and activity of TNF-alpha, IL-1beta and IL-6. Some glial inhibitors, which are safe and clinically well tolerated, are potential useful agents for treatment of neuropathic pain and for the prevention of tolerance to morphine analgesia. Targeting glial activation is a clinically promising method for treatment of neuropathic pain.