Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA.
Graduate Program in Health Sciences, Federal University of Sergipe, Aracaju/Se, Brazil.
Pain. 2017 Sep;158(9):1697-1710. doi: 10.1097/j.pain.0000000000000967.
Regular physical activity prevents the development of chronic muscle pain through the modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the N-methyl-D-aspartate receptor (p-NR1) and serotonin transporter (SERT) in the RVM. Mice that had performed 5 days of voluntary wheel running prior to the induction of the model were compared with sedentary mice. Sedentary mice showed significant increases in mechanical paw withdrawal frequency and a reduction in muscle withdrawal threshold; wheel running prevented the increase in paw withdrawal frequency. Naloxone-treated and MOR mice had increases in withdrawal frequency that were significantly greater than that in physically active control mice and similar to sedentary mice. Immunohistochemistry in the RVM showed increases in p-NR1 and SERT expression in sedentary mice 24 hours after the induction of the model. Wheel running prevented the increase in SERT, but not p-NR1. Physically active, naloxone-treated, and MOR mice showed significant increases in SERT immunoreactivity when compared with wild-type physically active control mice. Blockade of SERT in the RVM in sedentary mice reversed the activity-induced hyperalgesia of the paw and muscle. These results suggest that analgesia induced by 5 days of wheel running is mediated by mu-opioid receptors through the modulation of SERT, but not p-NR1, in RVM.
有规律的身体活动通过调节涉及腹内侧前脑束（RVM）的中枢机制来预防慢性肌肉疼痛的发展。我们测试了在活跃的小鼠中，物理活性阻断或基因缺失μ-阿片受体是否会在活动诱导的痛觉过敏模型中调节 RVM 中的兴奋性和抑制性系统。我们检查了对爪子机械刺激的反应频率、肌肉撤回阈值以及 RVM 中 N-甲基-D-天冬氨酸受体（p-NR1）和 5-羟色胺转运体（SERT）磷酸化的表达。与久坐的小鼠相比，在诱导模型之前进行了 5 天自愿轮跑的小鼠。久坐的小鼠表现出机械性爪子撤回频率显着增加和肌肉撤回阈值降低；轮跑可防止爪子撤回频率增加。纳洛酮处理和 MOR 小鼠的撤回频率增加明显大于活跃的对照小鼠，与久坐的小鼠相似。RVM 中的免疫组织化学显示，模型诱导后 24 小时久坐的小鼠中 p-NR1 和 SERT 的表达增加。轮跑可防止 SERT 增加，但不增加 p-NR1。与野生型活跃对照小鼠相比，活跃的、纳洛酮处理的和 MOR 小鼠的 SERT 免疫反应性显着增加。在久坐的小鼠中阻断 RVM 中的 SERT 可逆转爪子和肌肉的活动诱导性痛觉过敏。这些结果表明，5 天的轮跑诱导的镇痛是通过 RVM 中的 SERT 调节介导的，而不是通过 p-NR1 调节，而 SERT 调节是通过 SERT 调节介导的，而不是通过 p-NR1 调节。
