Short-duration physical activity prevents the development of activity-induced hyperalgesia through opioid and serotoninergic mechanisms.

Short-duration physical activity prevents the development of activity-induced hyperalgesia through opioid and serotoninergic mechanisms.
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DOI:
10.1097/j.pain.0000000000000967
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发表时间:
2017-09
期刊:
影响因子:
7.4
通讯作者:
Sluka KA
Sluka KA
中科院分区:
医学1区
文献类型:
--
作者:
Lima LV;DeSantana JM;Rasmussen LA;Sluka KA

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有规律的体力活动通过调节延髓吻侧腹内侧部(RVM)的中枢机制来预防慢性肌肉疼痛的发展。我们测试了在活动诱导的痛觉过敏模型中,药物阻断或身体活动小鼠的u-阿片受体基因缺失是否调节了RVM中的兴奋和抑制系统。我们检测了机械刺激对爪子的反应频率、肌肉收缩阈值,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)NR1亚单位的磷酸化表达。在模型诱导前进行了5天的自愿车轮运行的小鼠与久坐不动的小鼠进行了比较。久坐不动的小鼠表现出机械性撤爪频率的显著增加和肌肉撤退阈值的降低;车轮运动阻止了爪子撤退频率的增加。纳洛酮治疗组和MOR 2/2组小鼠戒断次数的增加明显大于体力活动对照组小鼠,与久坐小鼠相似。免疫组织化学结果显示,造模后24小时,久坐组小鼠肾小球内p-NR1和SERT的表达增加。车轮转动阻止了SERT的增加,但不能阻止p-NR1的增加。与野生型体力活动对照组小鼠相比,运动组、纳洛酮治疗组和MOR 2/2组小鼠的SERT免疫反应性显著增加。阻断久坐小鼠RVM中的SERT可逆转活动诱导的爪部和肌肉痛敏。这些结果表明,在RVM中,5天跑轮的镇痛作用是通过Mu-阿片受体调节SERT而不是p-NR1实现的。
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 2/2 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 2/2 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.
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