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Intracerebroventricular injection of propranolol blocked analgesic and neuroprotective effects of resveratrol following L5 spinal nerve ligation in rat

J Complement Integr Med. 2021 May 10;18(4):701-710. doi: 10.1515/jcim-2020-0393.

Abstract

Objectives: Resveratrol as a natural polyphenolic agent can alleviate neuropathic pain symptoms. The mechanism of analgesic activity of resveratrol is far from clear. The current study examine whether analgesic activity of resveratrol is mediated by its neuroprotective and anti-oxidant activity in the neuropathic pain. We further examine whether analgesic activity of resveratrol is mediated by β-adrenoceptors in the brain.

Methods: Neuropathic pain induced by L5 spinal nerve ligation (SNL). Male Wistar rats assigned into sham, SNL, SNL + resveratrol (40 μg/5 μL), and SNL + resveratrol + propranolol (a non-selective β-adrenoceptor antagonist, 30 μg/5 μL) groups. Drugs injected intracerebroventricular (ICV) at day SNL surgery and daily for 6 days following SNL. Thermal allodynia and anxiety examined on days of -1, 2, 4, and 6 following SNL. Electrophysiological study performed on day 6 following SNL for evaluation of resveratrol effects on sciatic nerve conduction velocity (NCV). The activity of catalase (Cat) and superoxide dismutase (SOD) enzymes in the brain assessed on days 6 following SNL.

Results: Resveratrol significantly decreased thermal allodynia (and not anxiety) in all experimental days. Additionally, resveratrol significantly increased NCV, and also normalized the disrupted Cat and SOD activities following neuropathic pain. Furthermore, propranolol significantly blocked the analgesic and neuroprotective effects of resveratrol.

Conclusions: It is suggested that the analgesic effects of resveratrol is mediated by its neuroprotective and antioxidant activities in the neuropathic rats. Furthermore, propranolol blocked the analgesic and neuroprotective effects of resveratrol.

Keywords: catalase enzyme; neuropathic pain; propranolol; resveratrol; superoxide dismutase enzyme.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Disease Models, Animal
  • Hyperalgesia / drug therapy
  • Ligation
  • Male
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Propranolol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Resveratrol
  • Spinal Nerves

Substances

  • Analgesics
  • Neuroprotective Agents
  • Propranolol
  • Resveratrol