阿片类药物的外周镇痛作用

阿片类药物的外周抗伤害和镇痛是通过外周阿片受体起作用。初级感觉神经元内存在着阿片受体，在炎症的条件下，阿片受体合成增加并转运到神经末梢，增强阿片类物质的外周作用。炎症部位的免疫细胞释放多种内源性阿片肽，作用于外周阿片受体产生抗伤害和镇痛作用。阿片肽代谢酶抑制剂也能增强阿片肽的外周作用。阿片类芗外周镇痛的临床研究正在进行。     

阿片类药物的外周镇痛作用

阿片类药物的外周抗伤害和镇痛是通过外周阿片受体起作用。初级感觉神经元内存在着阿片受体,在炎症的条件下,阿片受体合成增加并转运到神经末梢,增强阿片类物质的外周作用。炎症部位的免疫细胞释放多种内源性阿片肽,作用于外周阿片受体产生抗伤害和镇痛作用。阿片肽代谢酶抑制剂也能增强阿片肽的外周作用。阿片类药物外周镇痛的临床研究正在进行。     

外周炎症时大鼠背根神经节细胞μ-和κ-阿片受体mRNA的表达

目的观察外周炎症时大鼠背根神经节(dorsalrootganglion,DRG)细胞μ-和κ-阿片受体mRNA表达的变化。方法用角叉菜胶(carrageenan,CAR)在大鼠右后足皮下注射产生外周炎症,分别于正常和炎症后6、12、24和72h取右L4~5DRG。用原位杂交的方法观察正常及炎症期间DRG细胞μ-和κ-阿片受体mRNA表达的变化。结果正常大鼠的部分DRG细胞内可见μ-和κ-阿片受体mRNA表达。外周炎症后6h,表达μ-和κ-阿片受体mRNA的DRG细胞的数和μ-和κ-阿片受体mRNA表达量增加,24h表达量最高,72h下降至正常。结论外周炎症能使大鼠DRG细胞μ-和κ-阿片受体mRNA表达增加。提示外周炎症时大鼠DRG细胞μ-和κ-阿片受体合成增加。为阿片类物质应用于外周镇痛提供理论依据。     

椎管内镇痛药之间的相互作用

临床和实验研究发现椎管内应用阿片类药物和局麻药、α２－受体兴奋药之间，阿片药物之间；阿片类药物和其它药物之间存在协同和叠珈作用。临床椎管内应用阿片类药于慢性疼痛治疗发挥药物的协同镇痛作用，减少毒、副作用的产生。     

舒芬太尼对上肢手术病人罗哌卡因臂丛神经阻滞效果的影响

阿片类药物的外周作用越来越受到重视。动物实验证实,在免疫细胞和外周神经元表面均存在阿片受体。临床已证明阿片类药物可明显改善椎管麻醉的效果并延长镇痛时间。但使用阿片类药物与局麻药混合液用于外周神经阻滞的效果尚有争论。本研究拟评价0．5％罗哌卡因混合舒芬太尼12．5μg对臂丛神经阻滞效果的影响。     

丁丙诺啡与罗哌卡因混合液改善臂丛神经阻滞效果的临床观察

自从阿片受体在外周神经元表面发现以来，许多研究表明阿片类药物可通过其外周受体发挥镇痛作用。临床观察显示阿片类药物与局麻药合用，可明显改善椎管内麻醉的效果并延长镇痛时间，但使用阿片类药物与局麻药混合液用于外周神经阻滞的效果尚有争论。本研究采用随机双盲观察方法，评价丁丙诺啡与0．5％罗哌卡因混合液用于腋路臂丛神经阻滞效果和术后镇痛的影响。     

阿片类镇痛药的临床应用

阿片类药现已广泛用于疼痛治疗。本文就临床所用阿片类药物的治疗作用及受体机制进行讨论 ,最后对阿片类药的成瘾性研究以及实验性受体激动剂和拮抗剂的开发加以介绍。一、阿片类药物的镇痛机制和位点阿片类药物的镇痛机制涉及脊髓和脊髓以上多个中枢神经系统部位。吗啡和其它作用于 μ受体的阿片激动剂选择性的抑制多种伤害性反射 ,当鞘内给药或局部脊髓背角滴注时 ,镇痛效果显著 ,其它感觉传导通常不受影响。其机制至少包括三个以上 :①抑制位于传入神经末梢上的阿片受体所介导的神经递质释放 ,如Ｐ物质 ;②吗啡也拮抗外源性Ｐ物质 ,通过…     

新一代阿片受体拮抗剂-甲基纳曲酮

阿片类麻醉性镇痛药已广泛应用于围术期及晚期癌痛镇痛治疗。美国每年约有1．7亿张阿片类药处方，发现使用阿片类药物在减轻病人疼痛的同时，也出现不少副作用。为减免这些副作用，许多机构正在开发阿片类药的拮抗剂，目前常用的拮抗剂有纳络酮和纳曲酮，它们既是外周又是中枢阿片受体桔抗剂，因此在减弱阿片类药副反应的同时，     

乳铁蛋白混合吗啡对慢性神经病理性痛大鼠的镇痛作用

吗啡常用于中度及重度疼痛的治疗，疼痛患者中很多与神经病变有关。阿片类药物镇痛的主要机理是脊髓背角的传入纤维释放的兴奋性递质的突触前抑制。外周神经损伤后，部分伤害性感觉初级传入纤维发生变性，导致其中枢突触前膜上的阿片受体消失，阿片类药物的镇痛效应随之减弱。阿片类药物产生剂量依赖性的副作用，因此，阿片类药物常常与其它类镇痛药联合应用，以发挥其最大的镇痛效应，以降低副作用。鞘内注射乳铁蛋白混合吗啡对福尔马林诱导的外周炎症性痛大鼠产生协同镇痛效应。     

氯胺酮和艾司氯胺酮在低阿片方案中应用的研究进展

随着加速康复外科的不断发展,传统麻醉方案不断改进,有学者提出减少阿片类药物使用、推广多模式镇痛,即发展低阿片麻醉方案。氯胺酮是一种具有较强镇痛效果的麻醉药物,其药理学作用主要通过非竞争性地阻断N-甲基-D-天冬氨酸（NMDA）受体。因其具有较强的镇痛作用、不良反应较少、镇痛剂量不影响呼吸及循环稳定等特点,逐渐成为围术期低阿片方案中重要的非阿片类药物。本文就氯胺酮和艾司氯胺酮在低阿片方案中的临床应用及相关机制进行综述。     

Opioids as local anesthetic adjuvants for peripheral nerve block

Although the perineural application of opioids with local anesthetics has been of interest to anesthesiologists for years, neither the theoretical mechanism of action nor the effectiveness of this technique have been established. Opioid receptors are evident in the dorsal root ganglia (DRG), and central and peripheral endings of sensory afferents. Inflammation dramatically increases the production and axonal transport of these receptors. Local opioid injection in inflamed tissue is antinociceptive. Nevertheless, there is no evidence of opioid receptors in axonal membranes of afferent nerves in the portions of the axon where regional anesthesia is typically induced. Peripheral opioid injection produces modest analgesia in surgical patients when injected intraarticularly, and prolonged analgesia when injected locally into inflamed dental tissues, but has no effect in the absence of inflammation. Animal studies of perineural opioid application, in typical clinical concentrations, have shown no effect on sensory nerve action potentials. In the setting of acute, postoperative pain, the weight of evidence is against a significant clinical benefit from the addition of morphine, fentanyl, or sufentanil to local anesthetics for peripheral nerve block. Positive studies have often used injection sites close to the neuraxis or have not included systemic control groups. In a limited number of studies, perineural buprenorphine has produced prolonged analgesia. Basic opioid receptor research may ultimately provide a mechanism for perineural opioid activity. Alternatively we may determine that including opioids with local anesthetics for regional anesthesia is illogical and ineffective.     

Modulation of Peripheral Endogenous Opioid Analgesia by Central Afferent Blockade

Background: Peripheral tissue injury causes a migration of opioid peptide-containing immune cells to the inflamed site. The subsequent release and action of these peptides on opioid receptors localized on peripheral sensory nerve terminals causes endogenous analgesia. The spinal application of opioid drugs blocks the transmission of nociceptive information from peripheral injury. This study investigates the influence of exogenous spinal opioid analgesia on peripheral endogenous opioid analgesia.

Methods: Six and forty-eight hours after initiation of continuous intrathecal morphine infusion and administration of Freund's complete adjuvant into the hind paw of rats, antinociceptive and antiinflammatory effects were measured by paw pressure threshold, paw volume, and paw temperature, respectively. Inflammation and quantity of opioid-containing cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim stress-induced endogenous analgesia was examined 24 h after discontinuation of intrathecal morphine administration.

Results: Intrathecal morphine (10 [mu]g/h) resulted in a significant and stable increase of paw pressure threshold (P < 0.05) without changing inflammation, as evaluated by paw volume, paw temperature, and flow cytometry (P > 0.05). At 48 but not at 6 h after Freund's complete adjuvant, the number of [beta]-endorphin-containing cells and cold water swim-induced antinociception were significantly reduced in intrathecal morphine-treated rats compared with those treated with intrathecal vehicle (P < 0.05).     

Modulation of peripheral endogenous opioid analgesia by central afferent blockade

BACKGROUND: Peripheral tissue injury causes a migration of opioid peptide-containing immune cells to the inflamed site. The subsequent release and action of these peptides on opioid receptors localized on peripheral sensory nerve terminals causes endogenous analgesia. The spinal application of opioid drugs blocks the transmission of nociceptive information from peripheral injury. This study investigates the influence of exogenous spinal opioid analgesia on peripheral endogenous opioid analgesia. METHODS: Six and forty-eight hours after initiation of continuous intrathecal morphine infusion and administration of Freund's complete adjuvant into the hind paw of rats, antinociceptive and antiinflammatory effects were measured by paw pressure threshold, paw volume, and paw temperature, respectively. Inflammation and quantity of opioid-containing cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim stress-induced endogenous analgesia was examined 24 h after discontinuation of intrathecal morphine administration. RESULTS: Intrathecal morphine (10 micro g/h) resulted in a significant and stable increase of paw pressure threshold ( P< 0.05) without changing inflammation, as evaluated by paw volume, paw temperature, and flow cytometry ( P> 0.05). At 48 but not at 6 h after Freund's complete adjuvant, the number of beta-endorphin-containing cells and cold water swim-induced antinociception were significantly reduced in intrathecal morphine-treated rats compared with those treated with intrathecal vehicle ( P< 0.05). CONCLUSIONS: These findings suggest an interplay of central and peripheral mechanisms of pain control. An effective central inhibition of pain apparently signals a reduced need for recruitment of opioid-containing immune cells to injured sites.     

Peripheral nerve blocks of the face in children

The sensory innervation of the face is provided by the three major nerves, emerging from trigeminal nerve: the ophthalmic, maxillary and mandibular nerve. Nerve blocks of the face or head are not widely used in practice in France. However, regional anaesthesia has shown its value in terms of quality of analgesia and perioperative opioid economy in children and adults. Facial peripheral nerve blocks are divided into two categories: superficial trigeminal nerve blocks and deeper blocks such as the mandibular or suprazygomatic maxillary block. The performance of these blocks is simple provided the usual safety rules are followed. As for other peripheral nerve blocks, ultrasound guidance has shown its interest for the realization of facial nerve blocks to identify anatomical structure and to locate the spread of the injected local anaesthetic.     

Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis

Although most randomized clinical trials conclude that the addition of continuous peripheral nerve blockade (CPNB) decreases postoperative pain and opioid-related side effects when compared with opioids, studies have included relatively small numbers of patients and the majority failed to show statistical significance during all time periods for reduced pain or side effects. We identified studies primarily by searching Ovid Medline (1966-May 21, 2004) for terms related to postoperative analgesia with CPNB and opioids. Each article from the final search was reviewed and data were extracted from tables, text, or extrapolated from figures as needed. Nineteen articles, enrolling 603 patients, met all inclusion criteria. Inclusion criteria were a clearly defined anesthetic technique (combined general/regional anesthesia, general anesthesia alone, peripheral nerve block), randomized trial, adult patient population (> or =18 yr old), CPNB (or analgesia) used postoperatively (intrapleural catheters were deemed not to be classified as a peripheral nerve catheter), and opioids administered for postoperative analgesia in groups not receiving peripheral nerve block. Perineural analgesia provided better postoperative analgesia compared with opioids (P < 0.001). This effect was seen for all time periods measured for both mean visual analog scale and maximum visual analog scale at 24 h (P < 0.001), 48 h (P < 0.001), and 72 h (mean visual analog scale only) (P < 0.001) postoperatively. Perineural catheters provided superior analgesia to opioids for all catheter locations and time periods (P < 0.05). Nausea/vomiting, sedation, and pruritus all occurred more commonly with opioid analgesia (P < 0.001). A reduction in opioid use was noted with perineural analgesia (P < 0.001). CPNB analgesia, regardless of catheter location, provided superior postoperative analgesia and fewer opioid-related side effects when compared with opioid analgesia.     

Pain and the immune system

In inflammation, leucocytes containing opioid peptides migrate into the tissue. Opioid peptides can be released and bind to opioid receptors on peripheral nerve terminals, which counteracts inflammatory pain. Migration of opioid peptide-containing leucocytes is controlled by chemokines and adhesion molecules. Neurokinins, such as, substance P also contribute to the recruitment of these cells. Opioid peptide release from granulocytes can be stimulated by chemokines, such as, CXCR2 ligands. The release is dependent on intracellular calcium and activation of phosphoinositol-3 kinase and p38 mitogen activated kinase. Endogenous opioid peptides produced by leucocytes not only confer analgesia but recent evidence supports the concept that they also prevent the development of tolerance at peripheral opioid receptors. This review presents the discoveries that led to the concept of analgesia produced by immune-derived opioids.     

Role of afferent neural input in regression of sensory paralysis during epidural analgesia.

This study was designed to determine the role of the afferent peripheral neural input in the regression of sensory analgesia during epidural analgesia. Eighteen patients who underwent minor obstetric or gynecologic surgery under lumbar epidural analgesia with lidocaine were divided into three groups. Group A received electrical single twitch stimulation at the spinal nerve dermatome one segment rostrad of the proximal extent of sensory paralysis. Group B received electrical twitch stimulation at the anterior crural region where nerve block may have been most profound in this study. Group C was assigned as a control and did not receive any stimulation. The patients received the stimulation for 60 min (i.e., from 80 to 140 min after the epidural injection). The range of sensory analgesia at 140 min was compared with that at 80 min. The regression of sensory analgesia in group B or C was 1 +/- 0 (mean +/- SD) spinal nerve segments, but in group A it was 5 +/- 1, which was significantly (P less than 0.0025) larger than the others. We conclude that the afferent peripheral neural input to a spinal segment where the nerve block is incomplete may accelerate the regression of sensory analgesia from epidural analgesia.     

Peripheral nerve cathter techniques

Peripheral nerve catheters (PNC) or perineural catheters are used synonymously to describe placing a catheter in close proximity to nerve plexuses or individual nerves for the provision of continuous pain relief. The indications of PNCs extend beyond upper and lower extremity or thopaedic surgery to perioperative analgesia in patients undergoing a broad range of surgical procedures (e.g. abdominal, vascular, thoracic, breast and trauma surgeries). PNC use can facilitate early mobilization after surgery by providing high quality analgesia that in turn leads to reduced opioid consumption and associated opioid related side effects. Perioperative PNC analgesia can result in reduced length of in-hospital stay and improved rates of patient satisfaction. Insertion of peripheral nerve catheters can be done by either anaesthetist or surgeon. Long-term benefits are still to be ascertained. Risks are similar to those for peripheral nerve block, although catheter dislodgement remains a specific problem.     

Peripheral nerve catheter techniques

Peripheral nerve catheters (PNC) or perineural catheters are used synonymously to describe placing a catheter in close proximity to nerve plexuses or individual nerves for the provision of continuous pain relief. The indications of PNCs extend beyond upper and lower extremity orthopaedic surgery to perioperative analgesia in patients undergoing a wide range of surgical procedures (e.g. abdominal, vascular, thoracic, breast and trauma surgeries). PNC use can facilitate early mobilization after surgery by providing high quality analgesia that in turn leads to reduced opioid consumption and associated opioid related side effects. Perioperative PNC analgesia can result in reduced length of in-hospital stay and improved rates of patient satisfaction. Insertion of peripheral nerve catheters can be done by either anaesthetist or surgeon. Long term benefits are still to be ascertained. Risks are similar to peripheral nerve block although catheter dislodgement remains a specific problem.     

Does femoral nerve catheter placement with stimulating catheters improve effective placement? A randomized, controlled, and observer-blinded trial

Continuous peripheral nerve blocks offer the benefit of extended postoperative analgesia and accelerated functional recovery after major knee surgery. Conventional nerve localization is performed over a stimulating needle followed by blind insertion of the peripheral catheter. Correct catheter placement is confirmed by testing for satisfactory analgesia. Stimulating catheters offer the advantage of verifying correct placement close to the nerve during catheter placement. The aim of this randomized trial was to determine whether accurate catheter positioning under continuous stimulation accelerates the onset of sensory and motor block, improves the quality of postoperative analgesia, and enhances functional recovery. We compared femoral nerve catheters inserted under continuous stimulation with catheters that were placed using the conventional technique of blind advancement in 81 patients undergoing major knee surgery. Time of catheter placement was similar in both groups with 4 min (3/7.3; median, 25th/75th percentile) in the conventional group and 5 min (4/8.8) in the stimulating catheter group. In both groups, 42% of the catheters could be correctly placed (motor response of the patella with a current < or =0.5 mA) at first attempt. In 22 patients (58%) of the stimulating catheter group, the catheter had to be redirected 1-20 times, including 2 that could not be correctly placed within 20 min. The onset time of sensory and motor block was almost similar in both groups. There were no differences in the postoperative IV opioid consumption, and visual analog scale pain scores at rest and movement, or maximal bending and stretching of the knee joint during the 5 days after surgery. We conclude that with continuous femoral nerve blocks, blind catheter advancement is as effective as the stimulating catheter technique with respect to onset time of sensory and motor block as well as for postoperative pain reduction and functional outcome.