en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction:</strong> Hyperalgesia is among the current complications of diabetes mellitus; oxidative stress and inflammation were influential in its development. As an herbal component, Ellagic Acid (EA) has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hypernociception in Streptozotocin (STZ)-induced hyperglycemic rats.<br> <strong>Methods:</strong> Forty-eight male Wistar rats were divided into the control (receiving vehicle), hyperglycemic, EA (25 mg/kg)-treated control, EA (50 mg/kg)-treated control, EA (25 mg/kg)-treated hyperglycemic, and EA (50 mg/kg)-treated hyperglycemic groups. Hyperglycemia was induced by a single Intraperitoneal (IP) injection of STZ (60 mg/Kg). EA was administered daily by oral gavage for four weeks. The nociceptive response was assessed using Tail-Flick (TF) and Hot-Plate (HP) tests. Also, oxidative stress markers, including Malondialdehyde (MDA), Total Oxidant Status (TOS), and Total Antioxidant Capacity (TAC) in the serum, were evaluated.<br> <strong>Results:</strong> Hyperglycemic animals were found with significant changes, including a reduction in TF and HP latencies, an elevation in serum MDA level and TOS, and a decrease in serum TAC compared with controls. The treatment of hyperglycemic rats with EA facilitated the reduction of TF latency at the dose of 25 mg/kg and HP latency at 50 mg/kg. Furthermore, EA significantly increased TAC and decreased MDA level at a 50 mg/kg dose and reduced TOS at both doses in the serum of hyperglycemic animals. No significant alterations were found in the parameters studied in EA-treated normal rats.<br> <strong>Conclusion:</strong> These results displayed the antinociceptive effect of EA in hyperglycemic rats via attenuating oxidative stress. Therefore, EA appears to be a promising agent for managing. Hyperglycemic hypernociception.</div> Diabetes mellitus, Ellagic acid, Hyperalgesia, Rat, Oxidative stress 861 872 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2413-1&slc_lang=en&sid=1 Siamak Shahidi Siamakshahidi@yahoo.com 13700319475328460039229 13700319475328460039229 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Alireza Komaki Alirezakomaki@gmail.com 13700319475328460039230 13700319475328460039230 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Safoura Raoufi safooraraufi@yahoo.com 13700319475328460039231 13700319475328460039231 Yes Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Iraj Salehi irsalehi@yahoo.com 13700319475328460039232 13700319475328460039232 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Mohammad Zarei mmmzarei@yahoo.com 13700319475328460039233 13700319475328460039233 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Mohamadreza Mahdian mohamadrezamahdian@yahoo.com 13700319475328460039234 13700319475328460039234 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.