Bouaziz H, Tong C, Eisenach J C
Department of Anesthesia, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1009, USA.
Anesth Analg. 1995 Jun;80(6):1140-4. doi: 10.1097/00000539-199506000-00012.
Spinal neostigmine produces analgesia in chronically prepared rats, but not in sheep. However, since pain itself activates bulbospinal inhibitory pathways, neostigmine may be more effective in the postoperative period. We examined in sheep the antinociceptive effect of intrathecal neostigmine in the acute postoperative period and determined the muscarinic receptor subtype activated by neostigmine. A cervical intrathecal catheter was inserted via a laminotomy in 14 sheep that then received, in random order 1 mg of spinal neostigmine or saline on postoperative Day 1 and the other injection on postoperative Day 2. Three additional sheep received, on separate days, intrathecal neostigmine alone or with the muscarinic receptor subtype-specific antagonists pirenzepine (M1) 2 mg or AFDX-116 (M2) 2 mg. Antinociception was tested using a mechanical stimulus after each injection. Baseline withdrawal threshold did not change postoperatively. Intrathecal neostigmine, but not saline caused antinociception on both of the first two postoperative days. In contrast, intrathecal neostigmine caused no antinociception in another similar study performed at least 5 days after surgery. Pirenzepine, but not AFDX-116, abolished antinociception from neostigmine, suggesting an action on M1 subtype muscarinic receptors. Intrathecal neostigmine is antinociceptive in sheep during the acute postoperative period, and these data suggest that spinal cholinergic tone, and hence intrathecal neostigmine's analgesic effect, may be enhanced during the acute postoperative period.
脊髓注射新斯的明可使慢性制备的大鼠产生镇痛作用，但对绵羊无效。然而，由于疼痛本身会激活延髓脊髓抑制通路，新斯的明在术后可能更有效。我们在绵羊身上研究了鞘内注射新斯的明在术后急性期的抗伤害感受作用，并确定了新斯的明激活的毒蕈碱受体亚型。通过椎板切除术在14只绵羊中插入颈鞘内导管，这些绵羊在术后第1天随机接受1 mg脊髓新斯的明或生理盐水注射，在术后第2天接受另一种注射。另外3只绵羊在不同日期单独接受鞘内新斯的明注射，或与毒蕈碱受体亚型特异性拮抗剂哌仑西平（M1）2 mg或AFDX - 116（M2）2 mg联合注射。每次注射后使用机械刺激测试抗伤害感受作用。术后基线撤离阈值未发生变化。鞘内注射新斯的明而非生理盐水在术后的前两天均引起了抗伤害感受作用。相比之下，在术后至少5天进行的另一项类似研究中，鞘内注射新斯的明未引起抗伤害感受作用。哌仑西平而非AFDX - 116消除了新斯的明的抗伤害感受作用，提示其作用于M1亚型毒蕈碱受体。鞘内注射新斯的明在绵羊术后急性期具有抗伤害感受作用，这些数据表明脊髓胆碱能张力，以及鞘内新斯的明的镇痛作用，在术后急性期可能会增强。
