Stein C, Hassan A H, Lehrberger K, Giefing J, Yassouridis A
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.
Lancet. 1993 Aug 7;342(8867):321-4. doi: 10.1016/0140-6736(93)91471-w.
Opioids produce analgesia by interacting with local opioid receptors in peripheral inflamed tissue. This study investigated whether endogenous ligands of these receptors are present in synovia and whether such opioid peptides can inhibit pain by activation of intra-articular opioid receptors. Samples of synovium from 8 patients undergoing arthroscopic knee surgery were examined by immunohistochemistry for the presence of beta-endorphin, met-enkephalin, and dynorphin. All tissue samples showed synovitis. Inflammatory cells stained strongly for beta-endorphin and met-enkephalin but not for dynorphin. To find out whether blockade of intra-articular opioid receptors affected pain, we randomly assigned 22 patients undergoing arthroscopic knee surgery to receive naloxone (0.04 mg) intra-articularly (n = 10) or intravenously (n = 12); each patient received a placebo injection into the other site. Postoperative pain was assessed by visual analogue scale, a numerical rating scale, the McGill pain questionnaire, and supplementary analgesic consumption during the next 24 h. All pain scores were higher in the intra-articular naloxone group than in the intravenous naloxone group. The differences were significant (p < 0.05) during the first 4 h. Supplementary analgesic consumption was significantly higher in the intra-articular group (52.5 [14.0] vs 15.6 [8.0] mg diclofenac, p < 0.05). Opioid peptides are present in inflamed synovial tissue and can inhibit pain after knee surgery through an action specific to intra-articular opioid receptors. These findings expand the gate control theory of pain and suggest new approaches such as the development of peripherally acting opioid analgesics without central side-effects.
阿片类药物通过与外周炎症组织中的局部阿片受体相互作用产生镇痛作用。本研究调查了这些受体的内源性配体是否存在于滑膜中，以及此类阿片肽是否能通过激活关节内阿片受体来抑制疼痛。对8例接受膝关节镜手术患者的滑膜样本进行免疫组织化学检查，以检测β-内啡肽、甲硫氨酸脑啡肽和强啡肽的存在情况。所有组织样本均显示滑膜炎。炎症细胞β-内啡肽和甲硫氨酸脑啡肽染色强烈，但强啡肽染色阴性。为了确定关节内阿片受体的阻断是否会影响疼痛，我们将22例接受膝关节镜手术的患者随机分为两组，分别接受关节内注射纳洛酮（0.04 mg，n = 10）或静脉注射纳洛酮（n = 12）；每位患者在另一个部位接受安慰剂注射。术后疼痛通过视觉模拟评分、数字评分量表、麦吉尔疼痛问卷以及接下来24小时内的辅助镇痛药消耗量进行评估。关节内注射纳洛酮组的所有疼痛评分均高于静脉注射纳洛酮组。在前4小时内差异具有统计学意义（p < 0.05）。关节内注射组的辅助镇痛药消耗量显著更高（双氯芬酸52.5 [14.0] 对比15.6 [8.0] mg，p < 0.05）。阿片肽存在于炎症性滑膜组织中，并且可以通过关节内阿片受体的特异性作用抑制膝关节手术后的疼痛。这些发现扩展了疼痛的闸门控制理论，并提出了新的方法，如开发无中枢副作用的外周作用阿片类镇痛药。
