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

Metab Brain Dis. 2023 Apr;38(4):1421-1432. doi: 10.1007/s11011-023-01190-x. Epub 2023 Feb 22.

Abstract

Background: 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.

Aim: 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.

Methods: Rats were divided into six groups: (1) control, (2) CCI, (3) CCI + EA (50 mg/kg), 4) CCI + EA (100 mg/kg), 5) CCI + gabapentin (100 mg/kg), and 6) CCI + EA (100 mg/kg) + gabapentin (100 mg/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.

Results: CCI increased mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats which were reduced by treatment with EA (50 or 100 mg/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 100 mg/kg), gabapentin, or their combination.

Conclusion: 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.

Keywords: Chronic constriction injury; Ellagic acid; Gabapentin; Inflammation; Neuropathic pain; Neuroprotective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ellagic Acid / pharmacology
  • Ellagic Acid / therapeutic use
  • Gabapentin / metabolism
  • Gabapentin / pharmacology
  • Gabapentin / therapeutic use
  • Hyperalgesia* / drug therapy
  • Hyperalgesia* / metabolism
  • Neuralgia* / drug therapy
  • Neuralgia* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Gabapentin
  • Ellagic Acid
  • Tumor Necrosis Factor-alpha