Synergistic effect of ellagic acid and gabapentin in a rat model of neuropathic pain.

Abstract

Neuropathic pain is a subtype of chronic pain characterized by a primary lesion or dysfunction of the peripheral or central nervous system. The current pain management of neuropathic pain is inadequate and needs new medications. We studied the effects of 14 days of intraperitoneal ellagic acid (EA) and gabapentin administration in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the right sciatic nerve. Rats were divided into six groups: (1) control, (2) CCI, (3) CCI + EA (50mg/kg), 4) CCI + EA (100mg/kg), 5) CCI + gabapentin (100mg/kg), and 6) CCI + EA (100mg/kg) + gabapentin (100mg/kg). Behavioral tests, including mechanical allodynia, cold allodynia, and thermal hyperalgesia, were conducted on days - 1(pre-operation), 7, and 14 post-CCI. In addition, at day 14 post-CCI, spinal cord segments were collected to measure the expression of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and oxidative stress markers, including malondialdehyde (MDA) and thiol. CCI increased mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats which were reduced by treatment with EA (50 or 100mg/kg), gabapentin, or their combination. CCI increased TNF-α, NO, and MDA levels and decreased thiol content in the spinal cord, which all were reverted by administration of EA (50 or 100mg/kg), gabapentin, or their combination. This is the first report on ellagic acid's ameliorative effect in rats' CCI-induced neuropathic pain. This effect can be attributed to its anti-oxidative and anti-inflammatory, thus making it potentially useful as an adjuvant to conventional treatment.