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척수신경 결찰 모형에서 Morphine 내성 유도가 Gabapentin의 항이질통 효과에 미치는 영향
최금화 ( Jin Hua Cui ),이형곤 ( Hyung Gon Lee ),김웅모 ( Woong Mo Kim ),배홍범 ( Hong Beom Bae ),윤명하 ( Myung Ha Yoon ),최정일 ( Jeong Il Choi ) 대한마취과학회 2009 Korean Journal of Anesthesiology Vol.56 No.1
Background: Morphine is more effective in inflammatory or acute pain than neuropathic pain. Recently, some reports demonstrated that the development and maintenance of opioid tolerance and neuropathic pain have similar aspects. Here, we evaluated whether morphine tolerance affects the anti-allodynic effect of gabapentin in spinal-nerve ligated rat. Methods: Male Sprague-Dawley rats weighing 100-120 g received L5,6 spinal nerve ligation to induce neuropathic pain. Rats showing allodynia were implanted with intrathecal (i.t.) catheter to administer the experimental drugs into the subarachnoid space. To induce olerance to morphine, 15 μg of morphine was injected via i.t. catheter twice a day for 7 days, and the effect of i.t. gabapentin on the paw withdrawal threshold was examined using the von Frey test before and after the development of morphine tolerance. Results: Ligation of spinal nerves decreased the paw withdrawal threshold. Intrathecal morphine initially increased the paw withdrawal threshold, but this effect decreased gradually over time. However, morphine tolerance did not influence the effect of gabapentin on withdrawal threshold. Conclusions: Morphine tolerance did not affect gabapentin efficacay in a neuropathic pain model. (Korean J Anesthesiol 2009;56:74~8)
쥐의 포르말린 시험에서 척수강 Sildenafil의 항통각효과에 대한 GABA<sub>B</sub> 수용체 조절성
김웅모,윤명하,이형곤,한용구,김여옥,황란희,최금화,Kim, Woong Mo,Yoon, Myung Ha,Lee, Hyung Gon,Han, Yong Gu,Kim, Yeo Ok,Huang, Lan Ji,Cui, Jin Hua 대한통증학회 2007 The Korean Journal of Pain Vol.20 No.2
Background: A phosphodiesterase 5 inhibitor, sildenafil, has been effective against nociception. Several lines of evidence have demonstrated the role of the GABAergic pathway in the modulation of nociception. The impact of the GABA receptors on sildenafil was studied using the formalin test at the spinal level. Methods: Male SD rats were prepared for intrathecal catheterization. The formalin test was induced by subcutaneous injection of formalin solution. The change in the activity of sildenafil was examined after pre-treatment with GABA receptor antagonists ($GABA_A$ receptor antagonist, bicuculline; $GABA_B$ receptor antagonist, saclofen). Results: Intrathecal sildenafil dose-dependently attenuated the flinching observed during phase 1 and 2 in the formalin test. The antinociceptive effect of sildenafil was reversed by the $GABA_B$ receptor antagonist (saclofen) but not by the $GABA_A$ receptor antagonist (bicuculline) in both phases. Conclusions: Intrathecal sildenafil suppressed acute pain and the facilitated pain state. The antinociception of sildenafil is mediated via the $GABA_B$ receptor, but not the $GABA_A$ receptor, at the spinal level.
실험연구 : 쥐의 척수에서 Zaprinast의 항통각효과에 대한 아드레날린성 및 콜린성 수용체 역할
윤소정 ( So Jeong Yoon ),김여옥 ( Yeo Ok Kim ),황란희 ( Lan Ji Huang ),최금화 ( Jin Hua Cui ),허봉화 ( Bong Hwa Heo ),정성태 ( Sung Tae Jeong ),윤명하 ( Myung Ha Yoon ) 대한마취과학회 2007 Korean Journal of Anesthesiology Vol.53 No.1
Background: Spinal zaprinast, phospodiesterase inhibitor, has been shown to have an antinociception through an increase of cGMP. The aim of this study was to examine the role of spinal adrenergic and cholinergic receptors on the antinociceptive action of intrathecal zaprinast. Methods: Rats were implanted with lumbar intrathecal catheters. After formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. After observing the effect of intrathecal zaprinast, antagonism of intrathecal prazosin, yohimbine, atropine and mecamylamine for the effect of zaprinast were evaluated. Results: Intrathecal zaprinast produced a dose-dependent suppression of formalin-induced flinches in both phases of the formalin test. Intrathecal prazosin reversed the antinociception of zaprinast in phase 2, but not phase 1. Intrathecal yohimbine reversed the antinociception of zaprinast in both phases. Neither atropine nor mecamylamine reversed the antinocicetive action of zaprinast. Conclusions: Intrathecal zaprinast is against the nociceptive state evoked by formalin stimulus. Alpha 2 or alpha 1 adrenergic receptor, but not cholinergic receptors, may be related to the action of zaprinast in the spinal cord. (Korean J Anesthesiol 2007; 53: 85~90)