Role of naringenin in protection against diabetic hyperalgesia and tactile allodynia in male Wistar rats.

Hyperalgesia and allodynia are among the common manifestations of painful diabetic neuropathy. Naringenin (NA) has some biological activities, including anti-inflammatory, analgesic, and antidiabetic effects. We investigated the effects of NA administration at different doses, 20, 50, and 100 mg/kg, on streptozotocin (STZ)-induced hyperalgesia and allodynia in rats. The animals received saline or NA (20, 50, and 100 mg/kg, p.o.; once daily) for 8 weeks. Hyperalgesia was assessed by tail flick (TF) and formalin tests. Von Frey filaments were used for tactile allodynia evaluation. At the end, all rats were weighed and underwent plasma glucose and superoxide dismutase measurement. Diabetes caused significant hyperalgesia and allodynia during the above tests. NA 50 and 100 mg/kg reversed chemical and thermal hyperalgesia in diabetic rats. There were no significant differences in pain responses between NA (50 and 100 mg/kg)-treated diabetic rats and pregabalin-treated diabetic animals. Administration of NA 20 mg/kg did not alter pain-related behaviors in control and diabetic groups compared to the respective control ones. NA 50 and 100 mg/kg restored hyperglycemia as well as the decreased levels of (superoxide dismutase) SOD activity in diabetic rats. The body weight of treated diabetic rats increased significantly compared to untreated diabetics. Prolonged oral administration of NA (50 and 100 mg/kg) ameliorated some aspects of diabetic neuropathy by causing hypoglycemia and increasing the levels of antioxidant enzyme SOD. Therefore, NA makes a good candidate for treatment of diabetic neuropathy in clinical studies.