m-trifluoromethyl-diphenyl-diselenide and Pain

The organoselenium compound m-trifluoromethyl diphenyl diselenide (m-CF3-PhSe)2 has antinociceptive actions in several animal models, which are mediated by interaction with endogenous opioid systems. It also shows antidepressant-like action mediated by both opioid and serotonergic systems. Considering that serotonin (5-HT) plays an important role in the descending control of pain, this study further investigated the role of serotonergic systems in the antinociceptive action of (m-CF3-PhSe)2 in the glutamate-induced licking behavior model in mice. (m-CF3-PhSe)2 (1-50 mg/kg, p.o.), morphine (2.5 mg/kg, s.c.) or paroxetine (5 mg/kg, i.p.) reduced glutamate-induced nociception. Selective 5-HT1A and 5-HT2A receptor antagonists, WAY100635 (0.7 mg/kg, i.p.) and ketanserin (0.3 mg/kg, i.p.), but not the selective 5-HT3 receptor antagonist, ondansetron (0.5 mg/kg, i.p.), prevented the antinociceptive effect of (m-CF3-PhSe)2 (10 mg/kg) in the glutamate test. In biochemical studies, (m-CF3-PhSe)2 (10 and 50 mg/kg) decreased [(3)H]5-HT uptake in crude synaptosomes of mouse brains and slightly inhibited in vitro [(3)H]5-HT binding. In kinetic studies, the selenium (Se) distribution was determined at different time points after the administration of (m-CF3-PhSe)2 (500 mg/kg, p.o.) to mice. After 30 min, a high amount of Se was found in liver and kidneys, followed by the lung, red blood cells, serum and brain. A significant amount of Se accumulated in fat over the course of 8h. Urine was an important route of Se excretion originating from (m-CF3-PhSe)2. Collectively, results of this study indicate an involvement of the serotonergic systems in the antinociceptive effect of (m-CF3-PhSe)2 and a wide distribution of Se derived from this compound.

Topics: Analgesics; Animals; Female; Glutamic Acid; Mice; Organosilicon Compounds; Pain; Pain Measurement; Selenium; Serotonergic Neurons; Serotonin; Synaptosomes; Tissue Distribution

Pain is one of the most prevalent conditions, which limits productivity and diminishes quality of life. This study examined the antinociceptive effects of m-trifluoromethyl-diphenyl diselenide [(m-CF3-C6H4Se)2] on behavioral models of pain in mice. The involvement of opioid receptors in (m-CF3-C6H4Se)2-induced antinociception was evaluated in the tail-immersion test. (m-CF3-C6H4Se)2 exhibited significant inhibition of nociception induced by capsaicin (1.6 μg/paw, intraplantarly) (10-100 mg/kg, orally), and acetic acid (1.6%, 10 ml/kg, intraperitoneally) (1-100 mg/kg, orally), and in tail-immersion (50-100 mg/kg) and hot-plate (10-100 mg/kg) tests. The antinociception caused by (m-CF3-C6H4Se)2 in the tail-immersion test was significantly attenuated by naloxone (a nonselective opioid antagonist, 1 mg/kg, subcutaneously), naloxonazine (a selective μ-opioid receptor antagonist, 35 mg/kg, subcutaneously), or naltrindole (a selective δ-opioid receptor antagonist, 5 mg/kg, intraperitoneally). In contrast, (m-CF3-C6H4Se)2-induced antinociception was not affected by treatment with nor-binaltorphimine (a selective κ-opioid receptor antagonist, 10 mg/kg, subcutaneously) or naloxone methiodide (a peripherally restricted opioid antagonist, 1 mg/kg, subcutaneously). These results indicate that (m-CF3-C6H4Se)2-elicited antinociception in different models of pain through mechanisms that seem to involve an interaction with the central opioid system, more specifically μ-opioid and δ-opioid receptors.

Topics: Administration, Oral; Analgesics, Opioid; Animals; Behavioral Research; Capsaicin; Mice; Organosilicon Compounds; Pain; Pain Measurement; Receptors, Opioid, delta; Receptors, Opioid, mu; Sensory System Agents