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Introduction: Hyperalgesia is considered as one the marked signs of subchronic diabetes mellitus that could affect the life style of patients. Considering the evidence on the antidiabetic and analgesic effects of Nigella sativa (NS), this study was designed to investigate the analgesic effects of NS on formalin-induced nociceptive responses (standard formalin test) in streptozotocin (STZ)-induced diabetic rats. Methods: In this experimental study, male rats (n = 60) were randomly divided into control, NS-treated control, diabetic, sodium salicylate (SS)-treated diabetic, and NS-treated diabetic groups. For induction of diabetes, streptozotocin was used at a single dose. The treatment groups received oral administration of NS seed-mixed pelleted food (6.25%) for two months. Results: Diabetic rats exhibited a higher score of pain at both phases of the formalin test (p = 0.031 and p = 0.034 respectively) and NS-treated diabetic rats exhibited a lower nociceptive score as compared to untreated-diabetic ones at both acute and chronic phases (p = 0.008 and p = 0.009 respectively). Meanwhile, SS administration significantly reduced pain score only during the chronic phase of the test (p = 0.009). On the other hand, NS administration in control rats caused a lower nociceptive score as compared to untreated controls (p= 0.046 and p = 0.039). Conclusion: Two-month oral administration of NS seeds can attenuate nociceptive scores in an experimental model of diabetes mellitus and therefore could be considered as a potential treatment for painful diabetic neuropathy

Keywords: Nigella Sativa, Hyperalgesia, Diabetes mellitus, Streptozotocin, Rat

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