Lawrence A J, Joshi G P, Michalkiewicz A, Blunnie W P, Moriarty D C
Pain Research Institute, Liverpool, UK.
Eur J Clin Pharmacol. 1992;43(4):351-5. doi: 10.1007/BF02220608.
Intra-articular morphine (5 mg in 25 ml) was administered to patients for post-operative analgesia following arthroscopic knee surgery. At various time intervals, 30 min to 4 h post morphine, venous blood samples were taken in order to determine plasma levels of morphine and its primary metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Measurable amounts of morphine and morphine-3-glucuronide were found in the plasma of 7/10 patients whereas morphine-6-glucuronide was detected in only 2/10 patients. The plasma levels of morphine were lower than that regarded sufficient for post-operative analgesia in all but two patients, indicating a possibility of peripheral analgesia. In addition, synovial biopsy samples were assayed for the presence of opioid binding sites. Tissue samples from 11 different patients were analysed and 6/11 exhibited specific binding of [3H]naloxone, indicating the presence of opioid binding sites/receptors. The receptor type (i.e. mu-, delta- or k-) is at present unknown. Taken together, these data provide evidence that locally administered opiates can act on specific opioid receptors in the synovium to mediate analgesia.
关节内注射吗啡（25毫升含5毫克）用于膝关节镜手术后患者的术后镇痛。在吗啡注射后30分钟至4小时的不同时间间隔，采集静脉血样，以测定血浆中吗啡及其主要代谢产物吗啡-3-葡萄糖醛酸苷和吗啡-6-葡萄糖醛酸苷的水平。在10名患者中的7名血浆中发现了可测量的吗啡和吗啡-3-葡萄糖醛酸苷，而在10名患者中只有2名检测到吗啡-6-葡萄糖醛酸苷。除两名患者外，所有患者的血浆吗啡水平均低于术后镇痛所需的水平，提示存在外周镇痛的可能性。此外，对滑膜活检样本进行阿片类结合位点检测。分析了11名不同患者的组织样本，其中6/11显示出[3H]纳洛酮的特异性结合，表明存在阿片类结合位点/受体。目前尚不清楚受体类型（即μ、δ或κ型）。综上所述，这些数据提供了证据，表明局部应用阿片类药物可作用于滑膜中的特定阿片类受体以介导镇痛。
