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The Effect of Intrathecal Epigallocatechin Gallate on the Development of Antinociceptive Tolerance to Morphine

척수강 내로 투여한 Epigallocatechin Gallate이 모르핀의 항침해 작용에 대한 내성 발생에 미치는 효과

  • Kim, Woong Mo (Departement of Anesthesiology and Pain Medicine, College of Medicine, Chonnam National University) ;
  • Bae, Hong Beom (Departement of Anesthesiology and Pain Medicine, College of Medicine, Chonnam National University) ;
  • Choi, Jeong Il (Departement of Anesthesiology and Pain Medicine, College of Medicine, Chonnam National University)
  • 김웅모 (전남대학교 의과대학 마취통증의학교실) ;
  • 배홍범 (전남대학교 의과대학 마취통증의학교실) ;
  • 최정일 (전남대학교 의과대학 마취통증의학교실)
  • Received : 2009.07.28
  • Accepted : 2009.09.23
  • Published : 2009.12.01

Abstract

Background: A major ingredient of green tea is epigallocatechin-3-gallate (EGCG), and this is known to have many beneficial effects for cancer prevention and also on the cardiovascular system and neurodegenerative diseases through its anti-oxidant, anti-angiogenic, anti-inflammatory, lipid-lowering and neuroprotective properties. Its actions on nociception and the spinal nervous system have been examined in only a few studies, and in these studies EGCG showed an antinociceptive effect on inflammatory and neuropathic pain, and a neuroprotective effect in motor neuron disease. This study was performed to investigate the effect of EGCG on acute thermal pain and the development of morphine tolerance at the spinal level. Methods: The experimental subjects were male Sprague-Dawley rats and the Hot-Box test was employed. A single or double-lumen intrathecal catheter was implanted at the lumbar enlargement for drug administration. An osmotic pump was used to infuse morphine for 7 days for induction of morphine tolerance. EGCG was injected repeatedly for 7 days at twice a day through the intrathecal catheter. Results: Intrathecal EGCG increased the paw withdrawal latency (PWL) after repeated administration for 7 days at twice a day, but this did not happen with administering on single bolus injection of EGCG. In addition, the antinociceptive effect of intrathecal morphine was not affected by co-administration with EGCG. A continuous 7-day infusion of morphine caused a significant decrease of the PWL in the control group (M + S, morphine plus saline). In contrast, intrathecal EGCG injection over 7 days blocked the decrease of the PWL in the experiment group (M + E, morphine plus EGCG). Conclusions: Intrathecal ECGC produced a weak antinociceptive effect for acute thermal pain, but it did not change the morphine's analgesic effect. However, the development of antinociceptive tolerance to morphine was attenuated by administering intrathecal EGCG.

Keywords

Acknowledgement

Supported by : 전남대학교

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