In addition to the risk of developing opioid use disorder (OUD), known side-effects of long-term opioid use include chronic inflammation and hyperalgesia, which may arise from immune responses induced following chronic opioid use. To investigate this hypothesis, blood samples were obtained from individuals with chronic back pain who were either chronically taking prescription opioids or had minimal recent opioid exposure. Patient samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) against hydrocodone- or oxycodone-hapten conjugates to assess the levels of antibodies present in the samples. While no specific response was seen in opioid-naïve subjects, we observed varying levels of anti-opioid IgM antibodies in the exposed subjects. In these subjects, antibody formation was found to be weakly correlated with current reported daily opioid dose. Other drugs of abuse found to elicit an immune response have been shown to generate advanced glycation end-products (AGEs) through reaction with glucose and subsequent modification of self-proteins. Investigations into this potential mechanism of anti-opioid antibody production identified reduced the formation of reactive intermediate species upon norhydrocodone reaction with glucose in comparison with nornicotine, thus identifying potentially important differences in hapten processing to yield the observed adaptive immune response.

中文翻译：

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使用慢性阿片类药物治疗腰痛的个体中的抗阿片类抗体

除了发生阿片类药物使用障碍 (OUD) 的风险外，长期使用阿片类药物的已知副作用包括慢性炎症和痛觉过敏，这可能是由长期使用阿片类药物引起的免疫反应引起的。为了研究这一假设，我们从长期服用处方阿片类药物或近期阿片类药物暴露极少的慢性背痛个体中获取血液样本。使用针对氢可酮-或羟考酮-半抗原偶联物的酶联免疫吸附测定 (ELISA) 分析患者样品，以评估样品中存在的抗体水平。虽然在未使用阿片类药物的受试者中未观察到特异性反应，但我们在暴露的受试者中观察到不同水平的抗阿片类 IgM 抗体。在这些科目中，发现抗体形成与当前报道的每日阿片类药物剂量之间存在微弱相关性。其他被发现引起免疫反应的滥用药物已被证明通过与葡萄糖反应和随后的自身蛋白质修饰产生晚期糖基化终产物（AGEs）。对这种抗阿片类抗体产生的潜在机制的研究表明，与去甲烟碱相比，去甲氢可酮与葡萄糖反应时反应性中间体的形成减少了，从而确定了半抗原加工中潜在的重要差异，以产生观察到的适应性免疫反应。