Many HIV patients develop chronic pain and use opioid-derived medicine as primary analgesics. Emerging clinical evidence suggests that chronic use of opioid analgesics paradoxically heightens pain states in patients. This side effect of opioid analgesics has a significant negative impact on clinical practice, but the underlying pathogenic mechanism remains elusive. Using a mouse model of HIV-associated pain, we simulated the development of morphine exacerbation on pain and investigated potential underlying cellular and molecular pathways. We found that repeated morphine treatment promoted astrocyte activation in the spinal dorsal horn (SDH) and up-regulation of pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, we observed that morphine administration potentiated mitochondrial reactive oxygen species (ROS) in the SDH of the HIV pain model, especially on astrocytes. Systemic application of the ROS scavenger phenyl-N-t-butyl nitrone (PBN) not only blocked the enhancement of gp120-induced hyperalgesia by morphine but also astrocytic activation and cytokine up-regulation. These findings suggest a critical role of ROS in mediating the exacerbation of gp120-induced pain by morphine.

许多艾滋病毒患者出现慢性疼痛，并使用阿片类药物作为主要镇痛药。新出现的临床证据表明，长期使用阿片类镇痛药反而会加剧患者的疼痛状态。阿片类镇痛药的这种副作用对临床实践具有显着的负面影响，但其潜在的致病机制仍不清楚。使用艾滋病毒相关疼痛的小鼠模型，我们模拟了吗啡加剧疼痛的过程，并研究了潜在的潜在细胞和分子途径。我们发现重复吗啡治疗可促进脊髓背角 (SDH) 星形胶质细胞的激活以及促炎细胞因子 IL-1β 和 TNF-α 的上调。此外，我们观察到吗啡给药增强了 HIV 疼痛模型 SDH 中的线粒体活性氧 (ROS)，尤其是星形胶质细胞。全身应用ROS清除剂苯基-Nt-丁基硝酮（PBN）不仅可以阻断吗啡对gp120诱导的痛觉过敏的增强，还可以阻断星形胶质细胞的活化和细胞因子的上调。这些发现表明 ROS 在介导吗啡引起的 gp120 引起的疼痛加剧中发挥着关键作用。