A comparative study of serotonin and norepinephrine as adjuncts to improve cutaneous antinociception of mexiletine in response to skin pinpricks in rats.

5 - 羟色胺和去甲肾上腺素作为添加剂改善美西律对大鼠皮肤针刺反应的皮肤镇痛感受的比较研究。

• 影响指数: 3.298
• 发表时间: Jan-Dec 2021
• 来源期刊: Int J Immunopathol Pharmacol
• DOI: 10.1177/20587384211016129
• PMID: 33998312
• 文章类型: Comparative Study
• 中科院分区: Q4
• 方向: 医学
• 作者列表: Han M,Kang F,Yang C,Zhai M,Zheng K,Wang T,Liu Z,Li J

关键词: Coadministration; Serotonin; infiltrative cutaneous nociception; mexiletine; norepinephrine; pinpricks

Mesh: Analgesics / administration & dosage; Anesthetics, Local / administration & dosage; Animals; Dose-Response Relationship, Drug; Drug Combinations; Male; Mexiletine / administration & dosage; Norepinephrine / administration & dosage; Pain / drug therapy; Rats, Sprague-Dawley; Serotonin / administration & dosage; Skin / injuries; Rats

Abstract

As adrenaline, serotonin and norepinephrine are two other vasoconstrictors and both of which have been proved to increase the quality and duration of local anesthetics when added as adjuvants. However, the difference in the improvement of the nociception of local anesthetics between the two adjuvants remains unclear. The purpose of this study was to assess the cutaneous nociception of mexiletine by coadministration with serotonin and norepinephrine. Subcutaneous injection of drugs or combinations includes mexiletine 0.6, 1.8, 6.0 μmol, serotonin 1.6500 μmol, noradrenaline 0.8895 nmol, saline, mexiletine 1.8 and 6.0 μmol, respectively combined with serotonin 0.4125, 0.8250, 1.6500 μmol and noradrenaline 0.0356, 0.1779, 0.8895 nmol, with each injection dose of 0.6 ml. The nociception of mexiletine alone and mexiletine coadministered with serotonin and norepinephrine was assessed after subcutaneous injection. Subcutaneous injections of mexiletine elicited dose-related cutaneous antinociception (P < 0.05, 0.01, or 0.001). Compared with mexiletine (1.8 μmol), adding norepinephrine (except for lowest dose) and serotonin to mexiletine (1.8 μmol) solutions for skin nociceptive block potentiated and prolonged the action (P < 0.01 or 0.001). Mexiletine (6.0 μmol) combined with norepinephrine and serotonin extended the duration of cutaneous antinociception when compared with mexiletine (6.0 μmol) alone (P < 0.05, 0.01, or 0.001). Both serotonin and norepinephrine improve the sensory block and enhances the nociceptive block duration of mexiletine, and serotonin is superior to that of norepinephrine.

摘要

作为肾上腺素，5-羟色胺和去甲肾上腺素是另外两种血管收缩剂，当作为佐剂添加时，它们都被证明可以提高局部麻醉药的质量和持续时间。然而,两种佐剂在改善局部麻醉药的伤害性方面的差异尚不清楚。这项研究的目的是通过与5-羟色胺和去甲肾上腺素共同给药评估美西律的皮肤伤害感受。皮下注射药物或组合包括美西律0.6、1.8、6.0μmol，5-羟色胺1.6500μmol,去甲肾上腺素0.8895nmol,盐水,美西律1.8和6.0μmol，分别联合5-羟色胺0.4125、0.8250、1.6500μmol和去甲肾上腺素0.0356、0.1779、0.8895nmol,每次注射0.6毫升。皮下注射后评估单独的美西律和美西律与5-羟色胺和去甲肾上腺素共同给药的伤害性。皮下注射美西律可引起剂量相关的皮肤抗伤害感受(P<0.05、0.01或0.001)。与美西律（1.8μmol）相比，在美西律（1.8μmol）溶液中加入去甲肾上腺素（最低剂量除外）和5-羟色胺可增强和延长皮肤伤害性阻滞作用（P<0.01或0.001）。与单独使用美西律（6.0μmol）相比，美西律（6.0μmol）联合去甲肾上腺素和5-羟色胺可延长皮肤镇痛的持续时间（P<0.05，0.01或0.001）。5-羟色胺和去甲肾上腺素均可改善美西律的感觉阻滞，并增强美西律的伤害性阻滞持续时间，血清素优于去甲肾上腺素。