The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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The Effect of ATP-sensitive Potassium Channel on R-PIA Induced Mechanical Antiallodynia in a Peripheral Neuropathic Rat

신경병증 통증 모델의 백서에서 R-PIA의 기계적 항이질통 효과와 ATP-감수성 칼륨 통로와의 연관성에 대한 연구

  • Min, Hong Gi (Department of Anesthesiology and Pain Medicine, Asan Medical Center, Ulsan University School of Medicine) ;
  • Seong, Seung Hye (Department of Anesthesiology and Pain Medicine, Asan Medical Center, Ulsan University School of Medicine) ;
  • Jung, Sung Mun (Department of Anesthesiology and Pain Medicine, Asan Medical Center, Ulsan University School of Medicine) ;
  • Shin, Jin Woo (Department of Anesthesiology and Pain Medicine, Asan Medical Center, Ulsan University School of Medicine) ;
  • Gwak, Mi Jung (Department of Anesthesiology and Pain Medicine, Asan Medical Center, Ulsan University School of Medicine) ;
  • Leem, Jeong Gill (Department of Anesthesiology and Pain Medicine, Asan Medical Center, Ulsan University School of Medicine) ;
  • Lee, Cheong (Department of Anesthesiology and Pain Medicine, Asan Medical Center, Ulsan University School of Medicine)
  • 민홍기 (울산대학교 의과대학 마취통증의학교실) ;
  • 성승혜 (울산대학교 의과대학 마취통증의학교실) ;
  • 정성문 (울산대학교 의과대학 마취통증의학교실) ;
  • 신진우 (울산대학교 의과대학 마취통증의학교실) ;
  • 곽미정 (울산대학교 의과대학 마취통증의학교실) ;
  • 임정길 (울산대학교 의과대학 마취통증의학교실) ;
  • 이청 (울산대학교 의과대학 마취통증의학교실)
  • Received : 2005.09.22
  • Accepted : 2005.12.01
  • Published : 2005.12.10
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Abstract

Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.

Keywords

Acknowledgement

Supported by : 아산생명과학연구소

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