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Abstract Introduction: Chronic heterogeneous stress may be better for evaluation of the effect of chronic stress situations on the nociceptive behaviour. The present study investigated the effects of chronic heterogeneous sequential stress on thermal-induced nociception and formalin induced pain behavior in rats. Methods: In the present study, adult rats (220-300 g) were used. Animals were divided in stressed and non-stressed groups. Heterogeneous sequential stress including food deprivation, water deprivation, restraint, restraint at room temperature, restraint at 4 ͦ C, forced swimming and social isolation stress. Formalin and hot-plate tests were used as chemical and thermal pain model effects in rats, respectively. Results: While non-stressed animals gained weight during the experiments, stressed rats lost their weight. Chronic heterogeneous sequential stress significantly increased latency to hot-plate test when compared to control, while it increased the nociceptive behaviour in phase 2 of formalin test in male rats compared to control ones. Conclusion: The model of chronic heterogeneous sequential stress presented here may be useful in evaluating the basic mechanisms linking stress and pain and suggest a method to assess the potential therapeutic efficacy of drugs targeting painful disorders with a strong stress component.

Keywords: chronic heterogeneous stress, formalin test, hot-plate, rat

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