Hydrogen Peroxide Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors.
Hydrogen Peroxide Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors.
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DOI：
10.1097/aln.0000000000001756
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发表时间：
2017-10
期刊：
影响因子：
8.8
通讯作者：
Brennan TJ
中科院分区：
文献类型：
--
作者：
Sugiyama D;Kang S;Arpey N;Arunakul P;Usachev YM;Brennan TJ
过氧化氢（H2 O2）在皮肤创伤中具有多种作用，但在深部肌肉组织中的研究很少。基于足底切口后对瞬时受体电位锚蛋白1（TRPA 1）拮抗剂的反应，我们假设H2 O2通过TRPA 1在肌肉中发挥伤害性作用。在大鼠（n=269）和小鼠（n=16）的伤害性行为进行了评价后，不同浓度和体积的过氧化氢注射到腓肠肌或皮下组织。本实验观察了H_2O_2对26只大鼠和6只小鼠脊髓背角神经元活动和体外培养的腰段背根神经节（DRG）神经元的影响。肌肉内（平均值± SD：1436 ± 513秒）而非皮下（40 ± 58秒）注射H2 O2（100 mM，0.6 ml）可增加伤害感受时间。肌肉注射H2 O2（-143 ± 81秒）后，条件性位置厌恶明显，但皮下注射H2 O2（-2 ± 111秒）后，条件性位置厌恶不明显。这些H2 O2诱导的行为被TRPA 1拮抗剂阻断。肌肉注射H2 O2引起持续的背角神经元在体内的活动，和H2 O2激活DRG神经元在体外的一个子集。辣椒素神经阻滞降低足底切口后的保护，并减少肌肉注射H2 O2后的伤害性感受时间。TRPA 1基因敲除小鼠肌肉注射H2 O2后的伤害感受时间（173 ± 156秒）比野生型小鼠（931 ± 629秒）短。肌肉组织对H2 O2的更大反应可能有助于解释为什么包括深层肌肉的切口，而不仅仅是皮肤切口，会在伤害性通路中产生自发活动。
Hydrogen peroxide (H2O2) has a variety of actions in skin wounds but has been rarely studied in deep muscle tissue. Based on response to the Transient Receptor Potential Ankyrin 1 (TRPA1) antagonists after plantar incision, we hypothesized that H2O2 exerts nociceptive effects via the TRPA1 in muscle. Nociceptive behaviors in rats (n=269) and mice (n=16) were evaluated after various concentrations and volumes of H2O2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H2O2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia (DRG) neurons in vitro were evaluated from 26 rats and 6 mice. Intramuscular (mean ± SD: 1436 ± 513 seconds), but not subcutaneous (40 ± 58 seconds), injection of H2O2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (−143 ± 81 seconds), but not subcutaneous (−2 ± 111 seconds), injection of H2O2. These H2O2-induced behaviors were blocked by TRPA1 antagonists. Intramuscular injection of H2O2 caused sustained in vivo activity of dorsal horn neurons, and H2O2 activated a subset of DRG neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision, and reduced nociceptive time after intramuscular H2O2. Nociceptive time after intramuscular H2O2 in TRPA1 knockout mice was shorter (173 ± 156 seconds), compared with wild-type mice (931 ± 629 seconds). The greater response of muscle tissue to H2O2 may help explain why incision that includes deep muscle, but not skin incision alone, produces spontaneous activity in nociceptive pathways.