The pharmacodynamics of opioids for chronic peripheral neuropathic pain are complex and likely extend beyond classical opioid receptor theory. Preclinical evidence of opioid modulation of central immune signalling has not been identified in vivo in humans. Examining the cerebrospinal fluid (CSF) of patients medicated with opioids is required to identify potential pharmacodynamic mechanisms. We compared CSF samples of chronic peripheral neuropathic pain patients receiving opioids (n = 7) versus chronic peripheral neuropathic pain patients not taking opioids (control group, n = 13). Baseline pain scores with demographics were recorded. Proteome analysis was performed using mass spectrometry and secreted neuropeptides were measured by enzyme-linked immunosorbent assay. Based on Gene Ontology analysis, proteins involved in the positive regulation of nervous system development and myeloid leukocyte activation were increased in patients taking opioids versus the control group. The largest decrease in protein expression in patients taking opioids were related to neutrophil mediated immunity. In addition, notably higher expression levels of neural proteins (85%) and receptors (80%) were detected in the opioid group compared to the control group. This study suggests modulation of CNS homeostasis, possibly attributable to opioids, thus highlighting potential mechanisms for the pharmacodynamics of opioids. We also provide new insights into the immunomodulatory functions of opioids in vivo.

阿片类药物治疗慢性周围神经性疼痛的药效学很复杂，可能超出了经典的阿片类药物受体理论。阿片类药物调节中枢免疫信号的临床前证据尚未在人类体内发现。需要检查使用阿片类药物治疗的患者的脑脊液 (CSF) 以确定潜在的药效机制。我们比较了接受阿片类药物的慢性周围神经性疼痛患者（n  = 7）与未服用阿片类药物的慢性周围神经性疼痛患者（对照组，n = 13)。记录具有人口统计学的基线疼痛评分。使用质谱法进行蛋白质组分析，并通过酶联免疫吸附测定法测量分泌的神经肽。根据 Gene Ontology 分析，与对照组相比，服用阿片类药物的患者中参与神经系统发育和骨髓白细胞活化正调节的蛋白质增加。服用阿片类药物的患者中蛋白质表达的最大下降与中性粒细胞介导的免疫有关。此外，与对照组相比，在阿片类药物组中检测到的神经蛋白 (85%) 和受体 (80%) 的表达水平明显更高。该研究表明，可能归因于阿片类药物对 CNS 稳态的调节，从而突出了阿片类药物药效学的潜在机制。