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The Antiallodynic Effect and the Change of the α2 Adrenergic Receptor Subtype mRNA Expression by Morphine Administration in a Spinal Nerve Ligation Rat Model

백서의 척수신경결찰모델에서 Morphine의 투여가 항이질통 효과와 척수 α2 아드레날린계 수용체 아형 mRNA 발현에 미치는 영향

  • Chung, Kyu Yeon (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Shin, Sang Wook (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Kwon, Su Ah (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Kim, Tae Kyun (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Baek, Seung Hoon (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Baik, Seong Wan (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University)
  • 정규연 (부산대학교 의학전문대학원 마취통증의학교실) ;
  • 신상욱 (부산대학교 의학전문대학원 마취통증의학교실) ;
  • 권수아 (부산대학교 의학전문대학원 마취통증의학교실) ;
  • 김태균 (부산대학교 의학전문대학원 마취통증의학교실) ;
  • 백승훈 (부산대학교 의학전문대학원 마취통증의학교실) ;
  • 백승완 (부산대학교 의학전문대학원 마취통증의학교실)
  • Received : 2009.02.03
  • Accepted : 2009.03.25
  • Published : 2009.04.01

Abstract

Background: The neuropathic pain arising from nerve injury is difficult to treat and the therapeutic effects of opioid drugs remain debatable. Agonists acting at the ${\alpha}_2$ adrenergic and opioid receptors have analgesic properties and they act synergistically when co-administered in the spinal cord. The lack of subtype-selective pharmacological agents has previously impeded the synergistic effects that are mediated by the adrenergic receptor subtypes. Methods: We created neuropathic pain model by ligating the L5 spinal nerve in Sprague-Dawley rats (n = 18). We divided the rats into three groups (n = 6 for each group), and we administered intraperitoneal morphine (1 mg/kg, 3 mg/kg, 5 mg/kg) and then we measured the mechanical allodynia with using von-Frey filaments for 8 hours. We then injected morphine (5 mg/kg) intraperitoneally, twice a day for 2 weeks. We measured the tactile and cold allodynia in the morphine group (n = 9) and the saline group (n = 9). After 2 weeks, we decapitated the rats and harvested the spinal cords at the level of lumbar enlargement. We compared the ${\alpha}_2$ subtype mRNA expression with that of control group (n = 6) by performing real time polymerase chain reaction (RTPCR). Results: Intraperitoneal morphine reduced the neuropathic pain behavior in the dose-dependent manner. Chronic morphine administration showed an antiallodynic effect on the neuropathic pain rat model. The rats did not display tolerance or hyperalgesia. The expression of the mRNAs of the ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\alpha}_{2C}$ subtypes decreased, and morphine attenuated this effect. But we could not get statistically proven results. Conclusions: Systemic administration of morphine can attenuate allodynia during both the short-term and long-term time course. Morphine has an influence on the expression of ${\alpha}_2$ receptor subtype mRNA. Yet we need more research to determine the precise effect of morphine on the ${\alpha}_2$ subtype gene expression.

Keywords

Acknowledgement

Supported by : 부산대학교

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