Dugan Elizabeth A, Schachner Benjamin, Jergova Stanislava, Sagen Jacqueline
The Miami Project to Cure Paralysis, University of Miami, Miami, Florida, USA.
J Neurotrauma. 2021 Mar 15;38(6):789-802. doi: 10.1089/neu.2020.7378. Epub 2021 Jan 21.
Neuropathic pain often accompanies the functional deficits associated with spinal cord injury (SCI) and further reduces a patient's quality of life. Clinical and pre-clinical research is beginning to highlight the beneficial role that rehabilitative therapies such as locomotor training can have not only on functional recovery but also on chronic pain management. Our group has previously developed an intensive locomotor training (ILT) treadmill protocol on rats that reduced SCI neuropathic pain symptoms for at least 3 months. We have extended these findings in the current study to evaluate the ability of regular ILT regimen over a 2 year period post-SCI to maintain neuropathic pain reduction. To assess this, the rat clip compression SCI model (T7/8) was used and treadmill training was initiated starting 4 weeks after SCI and continuing through the duration of the study. Results showed continued suppression of SCI neuropathic pain responses (reduced mechanical, heat, and cold hypersensitivity throughout the entire time course of the study). In contrast, non-exercised rats showed consistent and sustained neuropathic pain responses during this period. In addition, prolonged survival and improved locomotor outcomes were observed in rats undergoing ILT as the study longevity progressed. Potential contributory mechanisms underlying beneficial effects of ILT include reduced inflammation and restoration of anti-nociceptive inhibitory processes as indicated by neurochemical assays in spinal tissue of remaining rats at 2 years post-SCI. The benefits of chronic ILT suggest that long-term physical exercise therapy can produce powerful and prolonged management of neuropathic pain, partly through sustained reduction of spinal pathological processes.
神经性疼痛常伴随脊髓损伤(SCI)相关的功能缺陷,进一步降低患者的生活质量。临床和临床前研究开始凸显诸如运动训练等康复疗法不仅对功能恢复而且对慢性疼痛管理所具有的有益作用。我们团队先前已在大鼠身上开发出一种强化运动训练(ILT)跑步机方案,该方案可减轻SCI神经性疼痛症状至少3个月。在当前研究中,我们扩展了这些发现,以评估SCI后2年期间定期进行ILT方案维持减轻神经性疼痛的能力。为评估这一点,使用了大鼠夹压SCI模型(T7/8),并在SCI后4周开始跑步机训练,持续至研究结束。结果显示,SCI神经性疼痛反应持续受到抑制(在整个研究过程中机械、热和冷超敏反应均减轻)。相比之下,未运动的大鼠在此期间表现出持续且稳定的神经性疼痛反应。此外,随着研究时间的延长,接受ILT的大鼠观察到生存期延长和运动结果改善。ILT有益作用的潜在促成机制包括炎症减轻以及抗伤害性抑制过程的恢复,这在SCI后2年对剩余大鼠脊髓组织进行神经化学分析时得到了证实。慢性ILT的益处表明,长期体育锻炼疗法可对神经性疼痛产生强大且持久的管理效果,部分是通过持续减轻脊髓病理过程实现的。