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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 and Objective: Paraquat toxicity can damage organisms through mechanisms that are not yet fully understood. Evidence shows that regular exercise and appropriate antioxidant supplements can help reduce the complications caused by paraquat toxicity. This study aimed to evaluate the effect of aerobic exercise training, along with piperine supplement, on the liver levels of tumor necrosis factor-alpha (TNF-a) and interleukin-10 (IL-10) in Wistar rats induced with paraquat.
Methods: In this experimental study, 40 adult Wistar rats were randomly placed into 5 groups of 8, including 1) sham, 2) negative control-paraquat, 3) paraquat + training, 4) paraquat + training + piperine, and 5) paraquat + piperine. Aerobic training included 7 weeks of walking on a treadmill (5 sessions per week for 30-40 min per session, at a speed of 10-18 m/min). Paraquat was administered to the rats by intraperitoneal injection at a dose of 5 mg/kg of body weight. The piperine supplement was daily gavaged at a dose of 10 mg/kg of body weight. The concentration of TNF-a and IL-10 was measured in the liver tissue.
Results: A significant increase in IL-10 and a decrease in TNF-a concentrations were observed between the paraquat-negative control groups compared to the sham, paraquat + exercise, paraquat + piperine, and paraquat + exercise + piperine groups (P<0.05). There was a significant difference between the mean concentrations of TNF-a in the liver tissue between the two negative control groups - paraquat with paraquat + piperine supplement (P<0.05), paraquat + exercise + piperine (P<0.05), paraquat + exercise (P<0.05), and sham (P<0.05). There was a significant difference in concentrations of IL-10 in the liver tissue between the two negative control groups - paraquat with paraquat + piperine supplement, paraquat + exercise + piperine, paraquat + exercise), and sham (P<0.05).
Conclusion: The concentration of TNF-a and IL-10 in male rats induced with paraquat were significantly decreased and increased, respectively, compared to paraquat + piperine supplement, paraquat + exercise + piperine, paraquat + exercise, and sham groups. Therefore, it seems that performing aerobic exercise, along with piperine supplementation, can be a proper way to reduce the inflammation caused by paraquat.