Antinociceptive Effect In Tail-flick Test Research Articles

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines

Context: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment.Objective: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action.Materials and methods: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30–180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1–8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence.Results: PC reduced (p < 0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE2. PC decrease total leukocyte migration (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and TNF-α (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively), besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p < 0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos-immunoreactive neurons in PAG.Discussion and conclusion: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.

Antinociceptive effects of combination of Tramadol and Acetaminophen on painful diabetic neuropathy in streptozotocin-induced diabetic rats

Objective The purpose of this study was to establish the streptozotocin (STZ)-induced diabetic model with rats and investigate the antinociceptive effect of combination of Tramadol (TR) and Acetaminophen (NAPA) on the animal model for the first time. Methods Diabetic model was induced by a single injection of STZ (60 mg/kg, intraperitoneal). Nociceptive thresholds were measured by means of electronic von Frey test, hot-plate test, and tail-flick test. On the 28th day of diabetes induction, diabetic rats with significant hyperalgesia were randomly divided into three groups: TR, NAPA, and TR-NAPA combination group. Each group was randomly divided into four subgroups. Three geometric series of drugs were given to each group respectively. Antinociceptive effects of the drugs were assessed at 15, 30, 60, 120, and 180 minutes after drug administration. 50% Maximum antinociceptive effect of each drug was determined by probit analysis, whereas interaction between TR and NAPA was evaluated by isobolographic analysis. Results Hyperalgesia, along with hyperglycemia, developed 4 days after STZ injection and persisted at all tested time points until 28 days. TR, NAPA, and TR-NAPA combination administration all produced dose-dependent antinociceptive effects. Isobolographic analysis showed a significant deviation of TR/NAPA 50% maximum antinociceptive effect (in tail-flick test, but not in von Frey test) from the additive line. Conclusions Combination of the two drugs produces an additive antinociceptive effect in tail-flick test, whereas probable additive antinociceptive effect in von Frey test in painful diabetic neuropathy rats.