No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia.
No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia.
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DOI：
10.1172/jci118852
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发表时间：
1996-08
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影响因子：
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通讯作者：
C. Stein;Martina Pflüger;A. Yassouridis;Jürgen Hoelzl;K. Lehrberger;Carmen Welte;A. Hassan
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文献类型：
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作者：
C. Stein;Martina Pflüger;A. Yassouridis;Jürgen Hoelzl;K. Lehrberger;Carmen Welte;A. Hassan
使用中枢作用阿片类药物治疗疼痛受到耐受性的限制。耐受性是随着药物或相关药物（例如，内源性）化合物作用于相同受体。这通常与受体的下调有关。在外周炎症组织中，局部表达的阿片肽和吗啡都可以通过相似的阿片受体群体介导产生强大的镇痛作用。我们推测，慢性存在的内源性阿片类物质在发炎关节可能传达下调外周阿片受体和耐受关节内吗啡的镇痛作用。我们评估了关节镜手术后的这些影响，有和没有组织学证实的滑膜细胞浸润的患者，我们检查滑膜阿片肽和阿片受体的免疫细胞化学和放射自显影，分别。我们发现，尽管在明显的滑膜炎中含有大量的含阿片样物质的细胞，但吗啡至少与没有这种细胞浸润的患者一样有效，并且外周阿片样物质受体没有明显的下调。因此，在发炎组织中表达的阿片样物质不会产生对外周吗啡镇痛的耐受性。外周作用阿片类药物的耐受性可能不如中枢作用阿片类药物明显，这为治疗关节炎和其他炎症性疾病中的慢性疼痛提供了一个有希望的前景。
Pain treatment with centrally acting opiates is limited by tolerance. Tolerance is a decreasing effect of a drug with prolonged administration of that drug or of a related (e.g., endogenous) compound acting at the same receptor. This is often associated with a downregulation of receptors. In peripheral inflamed tissue, both locally expressed opioid peptides and morphine can produce powerful analgesia mediated by similar populations of opioid receptors. We hypothesized that the chronic presence of endogenous opioids in inflamed joints might convey downregulation of peripheral opioid receptors and tolerance to the analgesic effects of intraarticular morphine. We assessed these effects after arthroscopic surgery in patients with and without histologically verified synovial cellular infiltration, and we examined synovial opioid peptides and opioid receptors by immunocytochemistry and autoradiography, respectively. We found that, despite an abundance of opioid-containing cells in pronounced synovitis, morphine is at least as effective as in patients without such cellular infiltrations, and there is no major downregulation of peripheral opioid receptors. Thus, opioids expressed in inflamed tissue do not produce tolerance to peripheral morphine analgesia. Tolerance may be less pronounced for peripherally than for centrally acting opioids, which provides a promising perspective for the treatment of chronic pain in arthritis and other inflammatory conditions.