Central and Local Administration of Gingko Biloba Extract EGb 761® Inhibits Thermal Hyperalgesia and Inflammation in the Rat Carrageenan Model

BACKGROUND: Oral administration of the standardized Ginkgo biloba extract EGb 761 (R) has been shown to inhibit thermal hyperalgesia in rodent models of inflammatory and postsurgical pain, but the mechanism underlying these effects is not known. We sought to determine the site of action of EGb 761 by investigating the antihyperalgesic and antiinflammatory properties of EGb 761 after local and central drug administration in the rat carrageenan model of inflammation. METHODS: Adult male Wistar rats received an intraplantar injection of carrageenan (3%) or saline into the left hindpaw followed 3 hours later by an intraplantar injection of EGb 761 (30, 100, or 300 mu g) or vehicle into the left paw; or intrathecal injection of EGb 761 (0.5, 1, 3, 10, or 100 mu g) or vehicle into the lumbar spinal cord region. Diclofenac (100 mu g) was administered as a positive control. Hindpaw withdrawal latency (in seconds) to thermal stimulation, response threshold (in grams) to mechanical stimulation, and paw volume were measured at 0, 2, 4, 6, and 24 hours after carrageenan injection. RESULTS: Both intraplantar (30, 100, and 300 mu g) and intrathecal (0.5 and 1 mu g) EGb 761 significantly inhibited carrageenan-induced thermal hyperalgesia and were equally as effective as diclofenac, but had no effect on mechanical hypersenitivity. Application >= 3 mu g EGb 761 to the spinal cord induced adverse behavioral effects, which precluded further nociceptive testing. Intraplantar (300 mu g) and intrathecal (1 mu g) EGb 761 also significantly reduced paw edema. CONCLUSION: These studies show that EGb 761 acts both at the site of inflammation and centrally at the spinal cord level to inhibit inflammation and thermal hyperalgesia, and may be useful in the treatment of inflammatory pain. (Anesth Analg 2011; 112: 1226-31)