The tail flick test is a common method used to evaluate acute pain in animal models. However, there seems to be a technical limitation to the use of this test, deserving a more detailed consideration. The problem is related to the use of physical restraints during the test, which in turn exposes the animal to stress and could therefore undesirably affect the obtained results. In the present report, a newly designed restraining chamber was used to improve the tail flick test regarding the mentioned limitation. Also, the baseline tail flick latency in animals undergoing the test using the classic restrainers was compared to that in those restrained by the newly designed chamber. The results indicated that the baseline tail flick latency was significantly lower in animals restrained by the newly designed box compared to those restrained by the tube-shaped version, which could be attributed to stress-induced analgesia. In conclusion, it is recommended that researchers use boxes similar to the custom-made box used in this study to prevent stress-induced errors when measuring nociceptive thresholds in rats.

Background - Benzodiazepines have been used with opiates to give better pain relief than opiates alone. However, the interaction between the two groups of drugs is controversial. The aim of this study was to investigate whether midazolam potentiated the antinociceptive effect of morphine. Methods - Male albino mice were used in this study. Antinociception was measured using the tail-flick test. Results - Midazolam and morphine caused dose-dependent antinociceptive effects in mice. The combination of midazolam and morphine showed an increase in analgesia. The benzodiazepine receptor antagonist, flumazenil, decreased the response induced by midazolam or midazolam plus morphine but not that of morphine alone. However, the opioid receptor antagonist naloxone, reduced the antinociception induced by morphine, midazolam, or a combination of the two drugs. Methysergide or propranolol increased the analgesic effect of midazolam; ketanserin, phenoxybenzamine and atropine did not. Conclusion - Midazolam induced antinociception through both benzodiazepine and opioid receptors.

Background: Gabapentin has been recently considered as an analgesic in neurpathic pain through spinal site of action. In addition co-administration of low dose of morphine with gabapentin, is proposed not only to reduce side effects, tolerance, and dependency of morphine but also has some analgesic effects. In this study, the analgesic effect of intracerebroventricular (ICV) gabapentin and its effect on morphine antinociception were investigated in tail-flick test. Methods: An intraventricular cannula was surgically inserted into ventricle space of rat brain. The latency time was measured after microinjection of 100, 300, 600 and 1000 mg of gabapentin or normal saline (sham). After determination of subanalgesic dose of gabapentin (300 mg), the combinational groups received subanalgesic and low dose of morphine (2 and 7 mg /kg) intraperitoneally, thirty minutes prior to gabapentin administration. Time response curve and Area Under the Curve (AUC), as antinociceptive index, were compared among the groups. Results: Intraventricular gabapentin showed analgesic effects at 600 mg (ICV). The combination of subanalgesic doses of gabapentin (300 mg ICV) and morphine (2 mg /kg i.p) increased significantly time-response curve and AUC compared to other groups. In addition, the analgesic response following co-administration of gabapentin (300 mg ICV) and analgesic dose of morphine was increased significantly compared to the sham and gabapentin group. Conclusion: The results demonstrated that intraventricular gabapentin has analgesic effect in transient model of pain and enhances morphine antinociception through cerebral site of action.