Department of Psychology, Texas A&M University, College Station, TX 77843-4235, USA.
Brain Behav Immun. 2011 Feb;25(2):349-59. doi: 10.1016/j.bbi.2010.10.018. Epub 2010 Oct 23.
Morphine is one of the most commonly prescribed medications for the treatment of chronic pain after a spinal cord injury (SCI). Despite widespread use, however, little is known about the secondary consequences of morphine use after SCI. Unfortunately, our previous studies show that administration of a single dose of morphine, in the acute phase of a moderate spinal contusion injury, significantly attenuates locomotor function, reduces weight gain, and produces symptoms of paradoxical pain (Hook et al., 2009). The current study focused on the cellular mechanisms that mediate these effects. Based on data from other models, we hypothesized that pro-inflammatory cytokines might play a role in the morphine-induced attenuation of function. Experiment 1 confirmed that systemic morphine (20 mg/kg) administered one day after a contusion injury significantly increased expression levels of spinal IL-1β 24 h later. Experiment 2 extended these findings, demonstrating that a single dose of morphine (90 μg, i.t.) applied directly onto the spinal cord increased expression levels of spinal IL-1β at both 30 min and 24 h after administration. Experiment 3 showed that administration of an interleukin-1 receptor antagonist (IL-1ra, i.t.) prior to intrathecal morphine (90 μg), blocked the adverse effects of morphine on locomotor recovery. Further, pre-treatment with 3 μg IL-1ra prevented the increased expression of at-level neuropathic pain symptoms that was observed 28 days later in the group treated with morphine-alone. However, the IL-1ra also had adverse effects that were independent of morphine. Treatment with the IL-1ra alone undermined recovery of locomotor function, potentiated weight loss and significantly increased tissue loss at the injury site. Overall, these data suggest that morphine disrupts a critical balance in concentrations of pro-inflammatory cytokines in the spinal cord, and this undermines recovery of function.
吗啡是治疗脊髓损伤（SCI）后慢性疼痛最常用的药物之一。然而，尽管广泛使用，但对 SCI 后使用吗啡的次要后果知之甚少。不幸的是，我们之前的研究表明，在中度脊髓挫伤损伤的急性期给予单次吗啡剂量会显著减弱运动功能，减少体重增加，并产生矛盾性疼痛的症状（Hook 等人，2009 年）。本研究集中于介导这些效应的细胞机制。基于其他模型的数据，我们假设促炎细胞因子可能在吗啡诱导的功能减弱中发挥作用。实验 1 证实，在挫伤损伤后一天给予全身吗啡（20mg/kg）会在 24 小时后显著增加脊髓 IL-1β 的表达水平。实验 2 扩展了这些发现，表明单次鞘内吗啡（90μg）给药会在给药后 30 分钟和 24 小时增加脊髓 IL-1β 的表达水平。实验 3 表明，在鞘内给予吗啡（90μg）之前给予白细胞介素 1 受体拮抗剂（IL-1ra）会阻断吗啡对运动恢复的不良影响。此外，预先用 3μgIL-1ra 预处理可预防单独用吗啡治疗组在 28 天后观察到的同水平神经病理性疼痛症状的表达增加。然而，IL-1ra 也有与吗啡无关的不良影响。单独用 IL-1ra 治疗会破坏脊髓中促炎细胞因子浓度的关键平衡，从而削弱功能的恢复。
总体而言，这些数据表明，吗啡会破坏脊髓中促炎细胞因子浓度的关键平衡，从而破坏功能的恢复。
