侧脑室或鞘内注射烟碱对恩氟烷催眠和镇痛作用的影响

目的初步分析恩氟烷的催眠和镇痛作用与神经元烟碱受体之间的关系。方法催醒实验:小鼠ip恩氟烷2.2mL.kg-1,翻正反射消失1min后,分别脑室注射烟碱10,20和40μg(5μL),记录翻正反射恢复时间(即睡眠时间)。镇痛实验:①甲醛实验:小鼠ip恩氟烷0.5mL.kg-1,5min后分别鞘内注射烟碱5,10和15μg(5μL),再5min后于足底皮下注射2%甲醛溶液20μL,记录60min内小鼠舔被注射足的累积时间。②热板实验:给药方法同甲醛实验,于注射烟碱后5,10,15,20和25min记录小鼠足部接触热板至开始添后足的时间作为后足痛阈。结果脑室注射烟碱能明显减少恩氟烷催眠小鼠的睡眠时间;鞘内注射烟碱不能拮抗甲醛实验中恩氟烷的镇痛作用,但可拮抗热板实验中恩氟烷的镇痛作用。结论神经元烟碱受体可能是恩氟烷催眠作用的重要靶位之一;也可能是恩氟烷对热刺激镇痛作用的重要靶位之一,而非对化学、炎性刺激镇痛作用的靶位。

Influence of intracerebroventricular or intrathecal injection of nicotine on hypnotic and analgesia effect of enflurane

AIM To investigate the relationship between neuronal nicotinic acetylcholine receptor and effects of analgesia and hypnosis induced by enflurane (EN) in mice. METHODS Analeptic test：mice received ip EN 2.2 mL·kg^-1. One minute after losing righting reflex, nicotine 0, 10, 20 and 40 μg dilluted in 5 μL artificial cerebrospinal fluid (ACSF) were intracerebroventricularly injected, and the time for the recovery of righting reflex (sleeping time) was recorded. Analgesic test: ① Formaldehyde test: 5 min after received ip EN 0.5 mL·kg^-1, mice were intrathecally injected nicotine 0, 5, 10 and 15 μg diluted in 5 μL ACSF, and another 5 min later, 2% formaldehyde 20 μL was injected subcutaneously into hind plantar. The accumulative time of licking injected paw was recorded from 0-10 min (phase Ⅰ) and 10-60 min (phase Ⅱ), respectively, and taken as analgesic time. ② Hot plate test: drug administrations were the same as in the formaldehyde test. The pain threshold (the time from mice were placed on the hot plate to licking paw) was recorded at 5, 10, 15, 20 and 25 min after administration of nicotine. RESULTS Intracerebroventricular injection of nicotine significantly decreased sleeping time in hypnotic mice induced by EN. Intrathecal injection of nicotine decreased significantly the pain threshold at the time points of 10 and 15 min in hot plate test, but did not affect analgesia induced by EN in formaldehyde test. CONCLUSION The neuronal nicotinic receptor may be one of the important targets of EN for hypnotism and analgesic effects in thermal nociceptive stimulation; but not for analgesic effect in chemical stimulus and inflammatory pain.