雷米芬太尼相关资料

1.长期给予吗啡后突然停药，会引起痛觉过在大鼠切口痛模型中.术前六天持续皮下给予纳洛酮20mg/kg/天会显著降低大鼠后爪的孺觉过敏o (Li X・Angst MS, Clark JD. Opioid-induccd
hyperalgesia and incisional pain. Ancsth Analg. 2001 Jul;93( 1):204-9.)
2.术中应用大剂量雷米芬太尼(0.40胞kg，min')比应用小剂虽雷米芬太尼{O.OSpg kg1 min1)更容易引起痛觉过敏，而应用小剂嫉氯胺桐(术前0.5mgAg.阐后5
pg kg 1 min \术后2 pg kg '・min '持续48小时)会防止痛觉过敏” (Joly V, Richebc P, Guignard B. et al. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2(X)5 Jul; 103( I ):147-55.)
3.通过对大鼠腰段脊隘切片进行电生理研究发现，不含甘氛酸辅料的盐酸宙米芬太尼不能诱发NMDA受体通道的电流.而甘氨酸(雷米芬太尼制剂中的常用辅料)可以i秀发NMDA 受体通道电流.而且这种通道电流可以被NMDA谷氨酸位点的特异性拈抗剂2 —基基一 5 一磷酸基戊酸(APV)阻断，而含有甘氨酸辅料的盐酸宙米芬太尼能够诱发与甘筮酸根本一样的NMDA受体通道电流，而且这种电流同样也可以被2—氛基一5—磷酸基戊酸(APV) 阻断，盐酸宙米芬太尼能够强化NMDA受体诱发的内向电流，而且这种强化作用可以被n 受体拮抗剂纳洛狷消除。

提示拈酸南米芬太尼不能宜接激活NMDA受体，但是可以通过阿片p受体强化NMDA通道的作用瑞芬太尼不能直接激活NMDA受体，瑞芬太尼使用后诱导的NMDA受体激活主要通过一条含p -阿片受体的调节通部来实现的，也就是说p -阿片受体起着—个桥梁作用。

(Guntz E. Dumont H. Roussel C. et al. Effects of remifentanil on N-melhyl-D-aspartale receptor: an electrophysiologic study in rat spinal cord. Anesthesiology. 2005 Jun; 102(6):1235-41.)：也有研究说明，雷米芬太尼对NMDA受体的这种作用仅是通过激活阿片5 受体实现的；(Zhao M, Joo DT. Enhancement of spinal N-methyl-D-aspariate receptor function by remifentanil action at delta-opioid receptors as a mechanism for acute opioid-induced hyperalgesia or tolerance. Anesthesiology. 20XX Aug; 109 (2): 308-17.)
4.NMDA受体是异源多聚体聚合物.在神经病理性疼痛和癌性疼痛中起着重要的作用.
< Saito 0. Aoc T. Kozikowski A. ct al. Ketamine and N-acctylaspartylglutamatc peptidase inhibitor exert analgesia in bone cancer pain. Can J Anaeslh. 2006 Sep;53(9):891-8.)： ( Melz AE, Yau HJ, Centeno MV, et al. Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. Proc Nall Acad Sci USA. 20XX Feb 17; 106(7):2423-8 )<> 其中调节亚单位中的NR2B 起者关键性作用(Zhang W. Shi CX, Gu XP. ei al. Ifenprcxlil induced antinociccption and decreased the expression of NR2B subunits in the dorsal horn after chronic dorsal root ganglia compression in rats. Anesth Analg. 20XX Mar;108(3): 1015-20.)
5.Celerier观察到一氧化领介他基例陂除小鼠.瑞芬太尼使用后所诱导的痛觉高微较野生型小鼠明显城弱。

此结果提示一氧化氮合解系统对术后急性疼痛和阿片诱导性痛觉高敏的发生过程中有促进作用，并将一氧化部•合酶系统和NMDA系统联系了起来。

术中应用雷米芬太尼会加重术后疼痛的程度，而•氧化氮合障系统起着重要作用。

(Celerier E. Gonzalez JR, Maldonado R, el al. Opioid-induced hyperalgesia in a murine mcxicl of postopcralivc pain: role of nitric oxide generated from the inducible nitric oxide synthase. Anesthesiology. 2006 Mar: 104(3):546-55.)
6.冲动剂激活的受体与G策白偶暇，引起细胞反响，随后被•系列G蛋白偶联受体激曲璘酸化，这些被磷酸化的G世白偶联受体作为底物用于结合调节蛋白B -arrestin.后者作为G 蛋白偶联受体信号的负调节因子•，能够使冲动剂引起的反响脱敏。

其它激主要是第二信使依赖性激油也在G蛋白偶联受体反响的脱敏中起假设重要作用o (G蛋白偶联受体减敏的主要机制是G蛋白偶联受体鼓励或笫二第二信使依赖性激曲或两者联合引起的G蛋白偶联受体磷酸化，)(Kelly E, Bailey CP, Henderson G Agonist-selective mechanisms of GPCR de^iensitization. Br J Pharmacol. 2(X)8 Mar: 153 Suppl 1:S379・88)
7.有证据说明阿片类药物诱导的促炎性胶欣细胞激活.可以对抗阿片类药物的慎痛作用. 引起阿片药物耐受和痛觉过枇，有可能是通过Toll样受体(TLR)4与ffiS样细胞分化赍白2(MD-2)产生作用o (Hutchinson MR, Zhang Y, Shridhar M, et al. Evidence lhal opioids may have (oll-like receptor 4 and MD-2 effects. Brain Behav Iminun. 20XX Jan;24( 1 ):83-95. Epub 2(X)9 Aug II.)
8.虽然推测阿片类药物所导致的痛觉过敏是由具有神经兴奋性的匍萄糖整昔代谢产物所引起，但是研究中发现，对经过盐酸纳曲甜预处理的小鼠和敲除ju 5和k受体的小鼠应用芬太尼，没有产生镇痛作用，但是伤害性缩腿反响潜伏期显著降低，这种痛觉过极能够被NMDA 受体阻断剂MK-801阻断。

由于芬太尼在体内进行生物转化时不产生任何葡萄糖酸昔代谢产物，因此，提示阿片类药物诱发产生的痛觉过敏叮能与具有神经兴奋性的葡萄糖醛昔代谢产物无关。

(Waxman AR・Arout C. Caldwell M. et al. Acute and chronic fentanyl a山ninistration causes hyperalgesia independently of opioid receptor activity in mice. Neurosci Lett. 20XX Oct 2:462(1):68-72)
9.p阿片受体与NMDA受体共同启动了痛觉过敏，但是维持仅是依靠NMDA受体的激活。

<Suarez-Roca H, Silva JA, Arcaya JL, Quintero L, el al. Role of mu-opioid and NMDA receptors in the dcvclopnwnt and maintenance of repeated swim stress-induced thermal hyperalgesia. Behav Brain Res. 2(X)6 Feb 28:167(2):205-11 >
10.纳洛酮在非常低剂州:的时候具有镇痛作用,而在较高剂址的时候不具备这种作用“(Sloan P, Hamann S. Ultra-low-dose opioid antagonists to enhance opioid analgesia. J Opioid Manag. 2006 Scp-Oct;2(5):295-304)
11.羟考酣与极低剂量的纳曲酮联合应用，能够产生很好的镇痛作用o (Webster LR. Butera PG・Moran LV. cl al. Oxytrcx minimizes physical dependence while providing effective analgesia: a randomized controlled trial in low back pain. J Pain. 2006 Dec;7( 12):937-46)
12.环丁甲羟氢吗啡(nalbuphine)与纳洛奥联合应用对患者妇科手术患者的术后疼痛仃好处。

<Gordon AT. Levine JD. Dubois MY. cl al. Open-label exploration of an intravenous nalbuphine and naloxone mixture as an analgesic agent following gynecologic surgery. Pain Med. 2(X)7 Scp;8(6):525-30)
13.小剂量纳洛阳参加到用于料从神经阻滞的利多卡因溶液中，无论该溶液中是否含有芬太尼，都会延长肾丛神经阻滞的镇痛时间0 (Movafegh A, Nouralishahi B, Sadeghi M, et al. An ultra-low
dose of naloxone added to lidocaine or lidocainc-fcntanyl mixture prolongs axillary- brachial plexus blockade. Anesth Analg. 2(X)9 Nov：109(5): 1679-83)
14. Anesthesiology. 20XX Mar; 108(3):484-94.
Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats. Van Elstractc AC. Sitbon P. Mazoit JX, Benhamou D.
University Paris-Sud. Assistance Publique-Hopitaux de Paris. Departement d'Anesthesie-Reanimation. Hopital de Bicetre. Le Kremlin-Bicetrc. France.
Comment in:
Anesthesiology. 2(X)8 Mar; 108(3):352-4.
BACKGROUND: Opioid-induced hyperalgesia can develop nipidly after opioid exposure. Neuropathic pain and opioid-induced hyperalgesia share common pathophysiologic mechanisms. Gabapentin is effective for the managcnwnt of neuropathic pain and may therefore prevent opioid-induced hyperalgesia. This study tested the effectiveness of gabapentin for prevention of long-lasting hyperalgesia induced by acute systemic fentanyl in uninjured rats. Involvement of the alpha2delta auxiliary subunits of voliage-gated calcium channels in the prevention of opioid-induced hyperalgesia by gabapentin also was a膈essed. METHODS: Hyperalgesia was induced in male Sprague-Dawley rats with subcutaneous fentanyl (four injections, 20, 60, or 100 micn)g/kg per injeclion at 15-rnin intervals). Intraperitoneal (30, 75, 150, or 300 mg/kg) or inlnithccal (300 microg) gabapentin was administered 30 min before or 300 min after (intnipcritoncal 150 mg/kg) the first fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure lest) was assessed on the day of the experiment and for several days after injections. The effects combining gabapentin with intrathecal ruihcnium red (20 ng) also were assessed. RESULTS: Fentanyl administration was followed by an early increase (analgesia) and by a later and sustained decrease (hyperalgesia) in nociceptive thresholds. Gabapentin did not significantly modify the early analgesic com,x)nent but dose-dependently prevented the delayed decrease in nociceptive threshold. Ruthenium red partially, but significantly^ opposed the prevention of opioid-induced hyperalgesia by gabapentin. IONS: Intraperitoneal and intrathecal gabapentin prevents (he development of hyperalgesia induced by acute systemic exposure to opioids. This prcvcnlion may result, at least in part, from binding of gabapentin to the alpha2dclta auxiliarj* subunits of voltagc-gatcd calcium channels.
1510. (Coquin J, Tafer N. Mazerolles M. et al. Pupillary dilatation monitoring to evaluate acute remifentanil tolerance in cardiac surgery. Ann Fr Anesih Reaniin. 2(X)9 Nov：28(l 1):930-5) Remifentanil is a powerful inorphinic agonist often ordered for anaesthesia. The use of peroperaiive large doses of this opioid increases the risk to develop postoperative hyperalgesia and acute tolerance. Bui how early these effects can occur? Despite the fad that these effects could be masked during the prcopcrativc time because of general anaesthesia,
it seems they could occur precociously. In order to try (o describe this lime, this study evaluated the acute tolerance under general anaesthesia requiring large doses of remifentanil by using an effective peropenitive monitoring of nociception: the continuous pupillary diameter monitoring. MATERIALS AND METHODS: In (his prospective observational clinical study, a continuous infusion of remifentanil was started a( a range of 0.3 rnicrog/kg/min after induction of anaesthesia by using propofol (TIVA), remifentanil bolus and cisalracurium. The pupil monitoring slarlcd 10 min lalcr (T+10 min) and lasted until the surgical incision (T+65 min). So. there was no surgical stimulus during this time. RESULTS: Thirty patients undergoing major cardiac or vascular surgery were included in this study. The continuous pupil diameter evaluation showed a significant increase of the pupil diameter from T+45 min. No significant variation of heart rate, blood pressure, bispcctra) index (BIS) values were observed. DISCUSSION: The development of acute remifentanil tolerance could possibly explain these results. If evaluations with continuous pupillary diameter monitoring are still limited, lhese results suggest that the use of powerful opioids such as remifentanil should be associated with a N-methyl-D-aspartate (NMDA) receptor antagonist agent, including short time administrations.。