H2O2通过瞬时受体电位锚蛋白1受体诱导肌肉的伤害感受

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H2O2 Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors

背景

H2O2在皮肤创伤中有各种各样的表现,但在深层肌肉组织中很少被研究。基于在足底的伤口后对瞬态受体电位锚蛋白1拮抗剂的反应,我们假设H2O2的作用是通过瞬态受体电位锚蛋白1在肌肉中产生伤害感受。

方  法

对大鼠(n=269)和小白鼠(n=16)的伤害性行为进行评估。不同的浓度和量的 H2O2被注入到腓肠肌或皮下组织中。评估了H2O2对26只大鼠和6只小鼠体内脊髓背角神经活动和腰背神经根神经节的影响。

结  果

肌内(mean ± SD: 1,436 ± 513 s)比皮下(40 ± 58 s)注入H2O2(100 mM, 0.6 ml) 增加了疼痛的时间。在肌内注入H2O2后(–143 ± 81 s)相对皮下注射(–2 ± 111 s)位置厌恶反应是明显的。这些H2O2诱导的行为被瞬时受体电位锚蛋白1拮抗剂阻断。 肌内注射H2O2引起了体内脊髓背角神经元的持续活动,H2O2激活了背根神经节神经元的一个亚群。在肌注H2O2后,辣椒素神经阻滞减少了足底切口的保护,减少了伤害性时间。肌注H2O2后在瞬时受体电位锚蛋白1基因敲除小鼠与野生型小鼠相比(931±629 s)疼痛时间短(173±156 s)。

结  论

肌肉组织对H2O2的更大的反应可能有助于解释为什么不单是皮肤上的切口,而是包括深肌肉的切口在伤害性感受中也会产生自发性的活动。

原始文献摘要

Sugiyama D1, Kang S, Arpey N, Arunakul P,  et al. H 2 O 2 Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors Anesthesiology.2017Oct;127(4):695-708.doi: .1097/ALN.0000000000001756.

Abstract

Background: H 2 O 2 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 antagonists after plantar incision, we hypothesized that H 2 O 2 exerts nociceptive effects via the transient receptor potential ankyrin 1 in muscle.

Methods: Nociceptive behaviors in rats (n = 269) and mice (n = 16) were evaluated after various concentrations and volumes of H 2 O 2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H 2 O 2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia neurons in vitro were evaluated from 26 rats and 6 mice.

Results: Intramuscular (mean ± SD: 1,436 ± 513 s) but not subcutaneous (40 ± 58 s) injection of H 2 O 2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (–143 ± 81 s) but not subcutaneous (–2 ± 111 s) injection of H 2 O 2 . These H 2 O 2 -induced behaviors were blocked by transient receptor potential ankyrin 1 antagonists. Intramuscular injection of H 2 O 2 caused sustained in vivo activity of dorsal horn neurons, and H 2 O 2 activated a subset of dorsal root ganglia neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision and reduced nociceptive time after intramuscular H 2 O 2 . Nociceptive time after intramuscular H 2 O 2 in transient receptor potential ankyrin 1 knockout mice was shorter (173 ± 156 s) compared with wild-type mice (931 ± 629 s).

Conclusions: The greater response of muscle tissue to H 2 O 2 may help explain why incision that includes deep muscle but not skin incision alone produces spontaneous activity in nociceptive pathways.

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