The role of α2-adrenoceptors of the medullary lateral reticular nucleus in spinal antinociception in rats

We attempted to find out the role of α₂-adrenoceptors of the medullary lateral reticular nucleus (LRN) in antinociception in rats. Spinal antinociception was evaluated using the tail-flick test, and supraspinal antinociception using the hotplate test. Antinociceptive effects were determined following local electric stimulation of the LRN, and following microinjections of medetomidine (an α₂-adrenoceptor agonist; 1–10 μg), atipamezole (an α₂-adrenoceptor antagonist; 20 μg) or lidocaine (4%) into the LRN. The experiments were performed using intact and spinalized Hannover-Wistar rats with a unilateral chronic guide cannula. Electric stimulation of the LRN as well as of the periaqueductal gray produced a significant spinal antinociceptive effect in intact rats. Medetomidine (1–10 μg), when microinjected into the LRN, produced no significant antinociceptive effect in the tail-flick test in intact rats. However, following spinalization, medetomidine in the LRN (10 μg) produced a significant atipamezole-reversible antinociceptive effect in the tail-flick test in the hot-plate test, medetomidine (10 μg) in the LRN produced a significant atipamezole-reversible increase of the paw-lick latency in intact rats. Microinjection of atipamezole (20 μg) or lidocaine alone into the LRN produced no significant effects in the tail-flick test. The results are in line with the previous evidence indicating brat the LRN and the adjacent ventrolateral medulla is involved in descending inhibition of spinal nocifensive responses. However, α₂-adrenoceptors in the LRN do not mediate spinal antinociception but, on the contrary, their activation counteracts antinociception at the spinal cord level. The spinal aninociceptive effect of supraspinally administered medetomidine in spinalized rats can be explained by a spread of the drug (e.g., via circulation) which then directly activates α₂-adrenoceptors at the spinal cord level.     

Activation of α2-adrenergic receptors decreases nerve trauma-induced afferent barrage but not autotomy

Effects of the selective α₂-adrenoceptor agonist, medetomidine, on a compound volley of a tibial nerve stimulation-evoked spinal reflex, pain-induced phrenic motor responses and on postoperative neuropathic pain behavior were studied in rats. Medetomidine (0.3 mg/kg) decreased the amplitude of the compound volley recorded from peroneal nerve in response to tibial stimulation in pentobarbital (40 mg/kg) anesthetized rats. Atipamezole, an α₂-adnenoceptor antagonist (1.5 mg/kg) fully restored the response when given 60 min after the medetomidine administration. Pain-evoked phrenic motor responses were completely inhibited upon combination anesthesia by pentobarbital (40 mg/kg) and medetomidine (0.3 mg/kg) (PB+M) but not upon plain pentobarbital anesthesia (50 or 60 mg/kg) (PB50, PB60). To study the effect of medetomidine on postoperative neuropathic pain behavior (autonomy), transection of sciatic nerve was done under PB+M, PB50 or PB60 anesthesia. No differences between the groups were found in the postoperative pain behavior during eight-week follow up. The results show that activation of α₂-adrenergic receptors by medetomidine under pentobarbital anesthesia mitigates trauma-induced afferent barrage, whereas it does not reduce the subsequent autotomy.     

丙泊酚靶控输注复合雷米芬太尼麻醉期间右旋美托咪啶对麻醉深度的影响

目的: 研究丙泊酚靶控输注复合雷米芬太尼麻醉期间,右旋美托咪啶(Dex)对脑电双频谱指数(BIS)和听觉诱发电位指数(AAI)的影响.方法:选择拟于全麻下行甲状腺次全切除术的年轻患者30例(ASA Ⅰ～Ⅱ级),诱导方法:以血浆药物浓度为靶目标进行丙泊酚靶控输注,靶浓度(Ct)为4 mg/L,同时静脉泵注雷米芬太尼1 μg/kg,待患者意识消失后静注罗库溴铵0.6 mg/kg,1 min后气管内插管.术中以雷米芬太尼0.2 μg/(kg·min)~(-1) 维持麻醉,定时追加肌松药,调节丙泊酚靶控输注的Ct值,使BIS维持在50±3;维持10 min稳定后将患者随机双盲分为两组:D组(n=15):Dex 0.4 μg/kg,用生理盐水稀释成5 ml静脉泵注(5 min),C组(对照,n=15):生理盐水5 ml,方法同D组.记录20 min内BIS、AAI、MAP、HR.结果:D组静注Dex后BIS由51.4±2.2逐渐下降,20 min时降为42.2±15.7(P<0.05);而AAI给药前15.1±3.3,20 min内没有明显变化;C组对照观察期间BIS、AAI均无明显变化.结论:丙泊酚靶控输注复合雷米芬太尼麻醉稳定后,静注Dex能使BIS进一步下降,而AAI保持不变.     

The antinociceptive action of an α2-adrenoceptor agonist in the spinal dorsal horn is due to a direct spinal action and not to activation of Descending Inhibition

In this electrophysiological study we tried to find out whether the spinal antinociceptive effect of a supraspinaly administered α₂-adrenoceptor agonist is due to a direct spinal effect or to activation of descending inhibition. The responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were studied following application of medetomidine, a selective α₂-adrenergic agonist, into the rostroventromedial medulla (RVM) or directly onto the spinal cord of the Intact and in spinal rats. The noxious electrical stimuli were applied to the ipsilateral receptive field in the plantar region of the hind paw, and responses mediated by A- and C-fibers to WDR neurons were separately evaluated. The reversal of medetomidine-induced effects was attempted by a systemic administration of atipamezole, a selective α₂-adronoceptor antagonist. Medetomldine injection into the RVM produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses to WDR neurons of the spinal dorsal horn in both intact and spinal rats. Paradoxically, the spinal aMFnociceptive effect of supraspinally administered medstomidine was stronger in spinal rats. The A-fiber-mediated responses were significantly less attenuated by medetomidine than the C-fiber-mediated responses to the WDR neurons. Also a direct application of medetomidine onto the spinal cord produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses, and this effect was identical in intact and in spinal rats. The medetomidins doses producing spinal antinociception were considerably lower with a direct spinal application than with a supraspinal application. These results indicate that spinal antinocicsption following spinal or supraspinal application of an α₂-adrenergic agonist is due to a direct activation of spinal α₂-adrenoceptors and not to descending inhibition. Activation of supraspinal α₂-adrenoceptors counteracts the spinal antinociceptive effect.     

右美托咪啶-异丙酚-芬太尼复合麻醉对颈椎手术病人体感诱发电位及运动诱发电位的影响

目的 评价右美托咪啶-异丙酚-芬太尼复合麻醉对颈椎手术病人体感诱发电位及运动诱发电位的影响.方法 择期全麻下行颈椎手术的病人36例,随机分为2组(n=18):异丙酚-芬太尼复合麻醉组(C组)和右美托咪啶-异丙酚-芬太尼复合麻醉组(D组).麻醉诱导:TCI异丙酚,血浆靶浓度为2μg/ml,静脉注射芬太尼1～2μg/kg,意识消失后经口置入喉罩进行通气.意识消失后D组经10 min静脉注射右美托咪啶0.5μg/kg,随后以0.5μg·kg-1·h-1的速率静脉输注至术毕,C组给予等容量生理盐水.分别于给予右美托咪啶前及静脉输注右美托咪啶10 min时记录体感诱发电位P15-N20波的波幅和潜伏期,并记录运动诱发电位的未引出情况.结果 与C组比较,D组P15-N20波的波幅和潜伏期差异无统计学意义(P＞0.05);两组运动诱发电位未引出率均为0.结论 右美托咪啶-异丙酚-芬太尼复合麻醉对颈椎手术病人体感诱发电位及运动诱发电位无影响.     

异丙酚芬太尼复合不同剂量右美托咪啶麻醉对老年患者血液动力学及脊髓诱发电位的影响

目的 探讨异丙酚芬太尼复合不同剂量右美托咪啶麻醉对老年患者血液动力学及对体感诱发电位(somatosensory evoked potentials,SEPs)、运动诱发电位(motor evoked potentials,MEPs)监测的影响.方法 择期全麻颈椎前路手术患者45例,依据右美托咪啶剂量按随机数字表法随机分成C组(对照组)、D1组(右美托咪啶浓度0.3 μg· kg-1·h-1) ;D2组(右美托咪啶浓度0.8 μg· kg-1·h-1).3组麻醉诱导方法相同.麻醉诱导:静脉注射咪达唑仑2 mg～3 mg、异丙酚Cp 1.5 mg/L(Marsh药代动力学参数)、芬太尼1.5μg/kg～2.0 μg/kg,患者意识消失后经口置入4号喉罩,行机械通气.D1、D2两组患者置入喉罩后给予右美托咪啶0.5 μg/kg静脉推注10 min完成,两组患者随即分别以0.3 μg·kg-1·h-1、0.8.μg· kg-1·h-1持续泵注至手术结束 ;C组患者以生理盐水代替右美托咪啶,其余用药同D组.术中调整异丙酚芬太尼用量维持脑电双频谱指数(BIS)值45 ～55之间,所有病例均不给入肌肉松弛剂,术中专人持续监测并记录SEPs、MEPs. 结果 D1、D2组患者应用右美托咪啶后心率减慢,平均动脉压(MAP)无明显变化.3组患者SEPs P15-N20的潜伏期、波幅均无统计学差异(P＞0.05).D2组患者有3例出现不同程度MEPs波形消失,阳性率为3/15,与D1组及C组(0/14)比较差异有统计学意义,且3例患者停用右美托咪啶20 min左右MEPs波形全部恢复.结论 右美托咪啶延长苏醒时间,减慢患者心率,其对老年患者SEPs影响轻微,但较大剂量应用对MEPs产生抑制作用.     

A fully noninvasive and robust experimental protocol for longitudinal fMRI studies in the rat

Functional magnetic resonance imaging (fMRI) is a unique tool to study brain activity and plasticity changes. Combination of blood-oxygen level-dependent (BOLD) fMRI and electrical forepaw stimulation has been used as a standard model to study the somatosensory pathway and brain rehabilitation in rats. The majority of fMRI studies have been performed in animals anesthetized with alpha-chloralose as functional-metabolic coupling is best preserved under this anesthesia. However, alpha-chloralose is not suitable for survival procedures due to side effects, limiting its use to single time point studies of the same animal. We therefore developed a new, totally noninvasive fMRI protocol, using sedation with the alpha2-adrenoreceptor agonist medetomidine in combination with transcutaneous monitoring of blood gases. The continuous subcutaneous administration of medetomidine resulted in stable physiological conditions over a long time and all animals tolerated the repetitive fMRI experiments well. A robust and reproducible, significant BOLD signal increase was observed upon forepaw stimulation in the contralateral primary somatosensory cortex in two consecutive medetomidine sessions in all rats, which was similar to the BOLD signal increase observed in the same animals under alpha-chloralose during a third independent session. Activation in the secondary somatosensory cortex was observed less frequently under both medetomidine and alpha-chloralose. No head motion artifacts or nonspecific brain activation was present. Sedation was quickly reversed by the administration of the antagonist atipamezole after the fMRI experiment. These results demonstrate that longitudinal fMRI studies can be performed safely under sedation with medetomidine to study functional recovery processes upon therapeutical treatment.     

Inhibition of opioid release in the rat spinal cord by alpha2C adrenergic receptors

Neurotransmitter receptors that control the release of opioid peptides in the spinal cord may play an important role in pain modulation. Norepinephrine, released by a descending pathway originating in the brainstem, is a powerful inducer of analgesia in the spinal cord. Adrenergic α_2C receptors are present in opioid-containing terminals in the dorsal horn, where they could modulate opioid release. The goal of this study was to investigate this possibility. Opioid release was evoked from rat spinal cord slices by incubating them with the sodium channel opener veratridine in the presence of peptidase inhibitors (actinonin, captopril and thiorphan), and was measured in situ through the internalization of μ-opioid receptors in dorsal horn neurons. Veratridine produced internalization in 70% of these neurons. The α₂ receptor agonists clonidine, guanfacine, medetomidine and UK-14304 inhibited the evoked μ-opioid receptor internalization with IC₅₀s of 1.7 μM, 248 nM, 0.3 nM and 22 nM, respectively. However, inhibition by medetomidine was only partial, and inhibition by UK-14304 reversed itself at concentrations higher than 50 nM. None of these agonists inhibited μ-opioid receptor internalization produced by endomorphin-2, showing that they inhibited opioid release and not the internalization itself. The inhibitions produced by clonidine, guanfacine or UK-14304 were completely reversed by the selective α_2C antagonist JP-1203. In contrast, inhibition by guanfacine was not prevented by the α_2A antagonist BRL-44408. These results show that α_2C receptors inhibit the release of opioids in the dorsal horn. This action may serve to shut down the opioid system when the adrenergic system is active.     

超声引导下不同佐剂对全髋关节置换术后镇痛效果的临床研究

〔摘 要〕 目的：研究超声引导下腰方肌阻滞中不同佐剂对全髋关节置换术（THA）术后镇痛效果的研究。方法：选取 佛山市第一人民医院 2019 年 12 月至 2020 年 12 月期间行 THA 的 90 例患者,采用随机分组的方法分成 Y 组、D 组和 R 组, 各 30 例。Y 组手术侧注入混合药：罗哌卡因 100 mg ＋右美托咪定 1 μg·kg-1（共 30 mL）,D 组手术侧注入混合药：罗哌 卡因 100 mg ＋地塞米松 0.1 mg·kg-1（共 30 mL）,R 组手术侧注入罗哌卡因 100 mg（共 30 mL）。各组患者术后均复合 静脉自控镇痛（PCIA）。术后根据镇痛效果静脉注射曲马多 50 mg 进行补救镇痛同时记录患者对术后镇痛的满意度评分。 记录三组患者术后 4、6、12、24、48 h 静息以及被动运动的视觉模拟评分法（VAS）评分。统计术后 48 h 内曲马多补救 镇痛情况和镇痛泵的按压次数。同时记录术后 48 h 内呼吸抑制、恶心呕吐以及术后谵妄的发生率。结果：术后 4、6、48 h 各组 VAS 评分比较,差异无统计学意义（P ＞ 0.05）。术后 12、24 h, Y 组、D 组的 VAS 评分均低于 R 组,差异具有统 计学意义（P ＜ 0.05）,且术后 12、24 h Y 组的 VAS 评分与 D 组比较,差异无统计学意义（P ＞ 0.05）;术后 48 h 内, Y 组、D 组的镇痛泵的按压次数为（1.5 ± 1.1）次、（1.1 ± 0.9）次,曲马多的补救例数为 2 例（6.7 %）、2 例（6.7 %）, 均低于 R 组的（3.5 ± 1.2）次及 8 例（26.7 %）,差异具有统计学意义（P ＜ 0.05）。且 Y 组的的曲马多的补救例数及镇痛 泵的按压次数与 D 组比较,差异无统计学意义（P ＞ 0.05）;呼吸抑制以及术后谵妄三组均未出现。Y 组恶心呕吐发生 1 例 （3.3 %）与 D 组的 2 例（6.7 %）,均低于 R 组的 7 例（23.3 %）,差异具有统计学意义（P ＜ 0.05）。且 D 组与 Y 组的 恶心呕吐率比较,差异无统计学意义（P ＞ 0.05）。术后 Y 组术后满意度评分为（5.8 ± 0.3）分、D 组为（5.3 ± 0.3）分, 均高于 R 组的（3.9 ± 0.5）分,差异具有统计学意义（P ＜ 0.05）。且 D 组与 Y 组的术后满意度评分比较,差异无统计学 意义（P ＞ 0.05）。结论：超声引导下腰方肌阻滞中加入佐剂（右美托咪定或地塞米松）对 THA 术后镇痛的效果更佳,同 时可以减少不良反应,提高患者对术后镇痛的满意度。但两者镇痛效果并无明显差别。     

右美托咪定用于腹腔镜胆囊切除术麻醉中的效果及安全性分析

目的探讨右美托咪定在腹腔镜胆囊切除术麻醉中的效果及安全性。方法将我院择期行腹腔镜胆囊切除术患者76例随机均分为对照组（气管插管后术前10min给予静脉泵注生理盐水）和实验组（气管插管后术前10min给予静脉泵注右美托咪定）,均以丙泊酚维持麻醉。比较术后两组患者入室、切皮、拔管时的心率和血压及丙泊酚维持用量和拔管时间。结果两组患者入室时的心率、血压比较无显著差异（P〉0.05）,但对照组在切皮、拔管时的心率和血压较实验组均明显上升（P〈0.05）;实验组丙泊酚维持用量明显低于对照组（P〈0.05）;术后拔管时间及术后烦躁发生率均低于对照组患者（P〈0.05）。结论右美托咪定用于腹腔镜胆囊切除术麻醉中具有效果明显、安全性高等优势,值得临床推广。