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Background: Damages to the peripheral fibers of sensory nerve cells and central neurons cause neuropathic pain. Manifestations of neuropathic pain occur in various conditions, including diabetes mellitus, chemotherapy, and as the side effects of some medications. Cressa cretica has long been used in traditional medicine for pain control. This study was conducted to determine the role of opioid receptors in the analgesic effect of the hydroalcoholic extract of C. cretica in an experimental model of neuropathic pain. Methods: The hydroalcoholic extract of C. cretica was prepared, and its total phenolic and flavonoid contents were standardized. Painful peripheral neuropathy was induced in rats by Chronic Constriction Injury (CCI) of the sciatic nerve. To evaluate the effects of the extract, the animals were orally given C. cretica extract (300 mg/kg), gabapentin (70 mg/kg) or normal saline (4 mL/kg) on days 3, 7, 14, and 21 after surgery, and behavioral tests were performed 45 minutes after taking the medications. To evaluate the role of the opioid receptors, Naloxone (1 mg/kg, IP) was given to rats treated with the extract 30 minutes after the extract and then the behavioral tests were performed after 15 minutes. Results: The hydroalcoholic extract of C. cretica attenuates neuropathic pain induced by CCI in rats. The extract works acutely and chronically, depending on the dosage and duration of use. Conclusion: The hydroalcoholic extract of C. cretica reduces CCI-induced neuropathic pain in rats, and Naloxone, as an opioid receptor antagonist, inhibits this effect.

Analgesic Effects of the Cressa Cretica Extract on Induced Neuropathic Pain in Rats, and the Potential Role of Opioid Receptors