Analgesic potency of intrathecally administered punicalagin in rat neuropathic and inflammatory pain models

Punicalagin, a natural polyphenolic compound classified as an ellagitannin, is a major ingredient of pomegranate (Punica granatum L.). Punicalagin has potent antioxidant and anti-inflammatory effects. Although the antinociceptive effects of orally administered pomegranate extracts have been reported, little is known about the effect of punicalagin on nociceptive transmission in the central nervous system. We examined whether punicalagin ameliorates neuropathic pain and inflammatory pain in the spinal cord. Male Sprague-Dawley rats were subjected to chronic constriction injury (CCI) of the sciatic nerve, and an intrathecal catheter was implanted for drug administration. The electronic von Frey test and cold-plate test were performed in CCI rats to evaluate mechanical and cold hyperalgesia in neuropathic pain, and the formalin test was performed in normal rats to evaluate acute and persistent inflammatory pain. An open-field test was conducted to explore whether punicalagin affects locomotor activity in CCI rats. Punicalagin administered intrathecally attenuated mechanical and cold hyperalgesia to the same degree as gabapentin in CCI rats and reduced pain-related behaviors in both the early and late phases in formalin-injected rats. Punicalagin did not affect motor function. These results suggest that punicalagin exerts an antinociceptive effect in the spinal cord without motor deficit, thus showing therapeutic potential for neuropathic pain and inflammatory pain.