Keates H L, Cramond T, Smith M T
School of Veterinary Science and Animal Production, University of Queensland, St Lucia, Australia.
Anesth Analg. 1999 Aug;89(2):409-15. doi: 10.1097/00000539-199908000-00030.
Small-dose (1 mg) intraarticular morphine has been used successfully in many studies to provide long-lasting analgesia after arthroscopic knee surgery. We used radioligand binding to determine whether these effects could be mediated by opioid binding sites in the joint, particularly after the induction of inflammation. Inflammation was induced by the injection of oleyl alcohol (20 microL) in sterile peanut oil (0.25 mL) into the left radiocarpal joint of 27 dogs, and the dogs were euthanized at 12 h. The articular and periarticular tissues from both treated and control joints were collected, and membranes were prepared for equilibrium binding assays. The density of specific opioid binding was markedly enhanced (P < 0.05) in homogenates prepared from the treated relative to those from the control joint. The binding affinities (KD values) for morphine and naloxone (mean +/- SEM) were approximately one one-hundredth (79 +/- 17 nM and 124 +/- 5.5 nM, respectively) that of the corresponding published affinities in brain tissue. However, the binding site densities were approximately one hundred times larger (Bmax = 1032 +/- 265 and 543 +/- 51 fmol/mg of protein) than the respective published values in brain tissue. These findings imply that the opioid binding sites, found in the inflamed articular and periarticular tissues in this study, are similar to those of putative mu 3-opioid binding sites that appear to be present on cultured thymocytes and in the airways of rats and humans.
The high density of opioid binding sites found in inflamed canine joint tissue supports the clinical use of intraarticular opioids in the treatment of postoperative and chronic inflammatory joint pain.
在许多研究中，小剂量（1毫克）关节内注射吗啡已成功用于在膝关节镜手术后提供持久的镇痛效果。我们使用放射性配体结合法来确定这些作用是否可由关节中的阿片类结合位点介导，尤其是在炎症诱导后。通过将20微升油醇注射到27只狗的左桡腕关节的无菌花生油（0.25毫升）中来诱导炎症，并在12小时后对狗实施安乐死。收集治疗关节和对照关节的关节及关节周围组织，并制备膜用于平衡结合测定。与对照关节制备的匀浆相比，治疗关节制备的匀浆中特异性阿片类结合的密度显著增强（P < 0.05）。吗啡和纳洛酮的结合亲和力（KD值，平均值±标准误）分别约为相应已发表的脑组织亲和力的百分之一（分别为79±17纳摩尔和124±5.5纳摩尔）。然而，结合位点密度比脑组织中各自已发表的值大约大一百倍（Bmax = 1032±265和543±51飞摩尔/毫克蛋白质）。这些发现表明，在本研究中发炎的关节和关节周围组织中发现的阿片类结合位点类似于培养的胸腺细胞以及大鼠和人类气道中似乎存在的假定μ3 -阿片类结合位点。
在发炎的犬关节组织中发现的高密度阿片类结合位点支持关节内使用阿片类药物治疗术后和慢性炎性关节疼痛的临床应用。
