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Background & Objective: Black pepper is frequently used in Iranian traditional medicine as an analgesic (E.g, for toothache). This investigation was conducted to evaluate the response of mice to pain induced by hot-plate and Formalin test either with or without Piperine (One of the active substances of the pepper). Materials & Methods: This randomized experimental study was performed on mice. Hot-plate and Formalin tests were planned to pain measurement. The mice were divided into 2 groups in each arm of study (Hot-plate and Formalin test group). The data of control (Saline) and drug (Piperine) groups were separately compared in each arm of study with student t-test and ANOVA. The difference between each point of data was considered significant at P-value under 0.05. Results: There was not a significant difference in tolerance time of subjects between hot-plate and saline groups. Piperine (25, 50 and 75 mg/kg) along with Morphine (10 mg/kg) causes significant increase to saline group in tolerance time and also significant increase to Morphine group, but in Formalin test Piperine could have significant effect in decreasing the pain induced by of Formalin on mice. These effects are comparable with Morphine. In Formalin test, pain has 2 phases. The first phase is acute and the 2nd one is chronic that begins from 15-20 minutes. Acute pain has central effect and chronic pain has peripheral pathway and Piperine causes decreasing response to Formalin test at the first phase of pain. Naloxone can prevent these effects in all groups. In Formalin test and hot-plate, the effect of Piperine were dose dependent. Conclusion: Piperine can centrally act on the nociception pathway and its effect on Opioid system exhibits as an enhancement Opioid effect. The effects are dose dependent and will be inhibited by Opioid antagonist.

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Background & Objective: Few studies concerning the effects of Opioid drugs on the function of immune system have been conducted and conflicting results have been reported. This study evaluates the in-vitro immune responses of drug abusers and investigates the pattern of production of IFN-? and IL-10, which represents the subsets of CD4+T-helper cells. Materials & Methods: Blood samples were taken from healthy drug addicted volunteers. Blood samples were also taken from healthy individuals with no history of drug abuse as control. Cell culture was performed in whole blood culture assay. Diluted blood samples were stimulated with phytohemagglutinin (PHA) and lipopolysaccharide (LPS) and the supernatants were collected to measure the Cytokine production. Results: The results demonstrated that a significant decrease in IFN-? production and increase in IL-10 production in Heroin addicts, whereas the production of these Cytokines in Opium addicts was not significant different from those in control group. Conclusion: The results indicated a significant decrease in mitogenic responsiveness of T-cells in Heroin addicts relative to control group, whereas mitogenic responsiveness of T-cells in Opium addicts was not significantly different from control group.

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Background and Objective: Methadone is a synthetic opioid which is used in opium addiction therapy and relief of acute and chronic pain. Side effects of Methadone were reported on heart and induction of Torsade De Pointes disease and increase QTc interval in electrocardiogram. This study was conducted to determine the effect of Methadone therapy on QTc interval in electrocardiogram and its relationship with dosage and duration of Methadone therapy. Method: This cohort study was conducted on 60 opium addicted patients (57 males, 3 females) whom referred to “Methadone Therapy Clinic” in 5 Azar teaching hospital in Gorgan, northern Iran during 2009-10. Patients were divided to three groups based on the dosage of methadone: 0-35 mg (27 cases), 35-55 mg (27 cases) and 55-120 mg (26 cases) per day. QTc interval in electrocardiogram was measured at the beginning of study, one month and 5 months afterward. Results: The mean±SD of QTc interval in patients at the beginning, one month and 5 months afterward of study was 0.42±0.027, 0.43±0.029 and 0.43±0.041 seconds, respectively. There was a significant increase in QTc interval after one month of methadone therapy, compared to the beginning of study. There was no significant difference in QTc interval between 1 month and 5 months following methadone therapy. There was no significant difference between QTc interval and different dosage of methadone. Conclusion: Methadone therapy increase QTc interval but there is not any relationship between dosage and duration of methadone therapy and QTc interval.

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Background and Objective: Chronic use of opioids leads to analgesic tolerance. Protein kinase C (PKC), adenylyl cyclase (AC), nitric oxide (NO) and glycogen synthase kinase 3 beta (GSK-3β) are involved in morphine tolerance. Lithium activates the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway that inhibits GSK-3β and reduces morphine-induced tolerance. This study was performed to evaluate the effects of lithium on morphine dependence symptoms and tolerance of its analgesic effects in Swiss mice by GSK-3β signaling.
Methods: This experimental study was performed on 56 Swiss male albino mice that were randomly allocated into 8 groups (each containing 7 mice). The intraperitoneal injection of morphine at different concentrations (50, 50 and 75 mg/kg) and different hours (08:00, 11:00 and 16:00, respectively) was performed for 4 days, and a single dose 50 mg/kg was administered on the 5th day. The effects of three doses of lithium (1, 5 and 10 mg/kg) given orally, 45 min before morphine injections on morphine-induced analgesic tolerance were evaluated. To evaluate analgesia latency on day 1, 3 and 5, tail flick and hot plate tests were done. The brain of each animal was removed to measure nitrite levels, and histological evaluation and immunohistochemistry for p-glycogen synthase (p-GSSer640) were performed on the last day of the study.
Results: Co-administration of lithium significantly increased the latency of analgesia in comparison with the morphine group on the 3rd and 5th day (P<0.05). Lithium reduced the morphine-induced increase of nitrite levels and also reduced brain damage. In addition, immunohistochemistry assay of p-GSSer640 indicated a significant reduction of the morphine-induced phosphorylation of GS at S640 by GSK in the lithium-treated mice.
Conclusion: Lithium administration can reduce morphine tolerance in adult male Swiss mice.