Nishiyama Tomoki, Matsukawa Takashi, Hanaoka Kazuo
Department of Anesthesiology, The University of Tokyo, Faculty of Medicine, Tokyo, Japan.
Can J Anaesth. 2004 Nov;51(9):899-904. doi: 10.1007/BF03018887.
Propofol is thought to act on gamma-aminobutyric acid receptors, which have some role in pain transmission in the spinal cord. In this study, we examined the effects of intrathecal propofol on acute thermally- or inflammation-induced pain in rats.
Lumbar intrathecal catheters were implanted in Male Sprague-Dawley rats. The tail withdrawal response to thermal stimulation (tail flick test) or paw flinching and shaking response by sc formalin injection into the hind paw (formalin test) were tested. Propofol 1000, 300 or 100 microg or saline (control) was administered as 10 microL intrathecally. Motor disturbance and behavioural side effects were also monitored in the rats during the tail flick test. Eight rats were used for each dose in each test.
No analgesic effects were observed in the tail flick test. In the formalin test, 50% of effective doses were 449 mug (95% confidence interval, 80-3180 microg) in phase 1 and 275 microg (146-519 microg) in phase 2. Motor disturbance was observed in one rat with 100 microg and agitation and allodynia were seen in one rat with 300 microg. However, both were reversible in 120 min.
Intrathecal administration of propofol had analgesic effects on inflammation-induced acute and facilitated pain but not on thermally-induced acute pain. Transient motor and sensory disturbance could not rule out the possibility of neurotoxicity.
丙泊酚被认为作用于γ-氨基丁酸受体,该受体在脊髓疼痛传递中起一定作用。在本研究中,我们检测了鞘内注射丙泊酚对大鼠急性热诱导或炎症诱导疼痛的影响。
将腰椎鞘内导管植入雄性Sprague-Dawley大鼠。测试对热刺激的甩尾反应(甩尾试验)或通过后爪皮下注射福尔马林引起的爪退缩和抖动反应(福尔马林试验)。鞘内注射10微升1000、300或100微克丙泊酚或生理盐水(对照)。在甩尾试验期间还监测大鼠的运动障碍和行为副作用。每个试验中每个剂量使用8只大鼠。
在甩尾试验中未观察到镇痛作用。在福尔马林试验中,第1阶段50%有效剂量为449微克(95%置信区间,80 - 3180微克),第2阶段为275微克(146 - 519微克)。100微克组有1只大鼠出现运动障碍,300微克组有1只大鼠出现激动和异常性疼痛。然而,两者在120分钟内均可逆转。
鞘内注射丙泊酚对炎症诱导的急性和易化性疼痛有镇痛作用,但对热诱导的急性疼痛无作用。短暂的运动和感觉障碍不能排除神经毒性的可能性。