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Ph1和吗啡诱导的镇痛过程中脑活动的映射

Mapping of Brain Activity in the Analgesia Induced by Ph1 and Morphine.

作者信息

Diniz Danuza Montijo, Malamut Carlos, Araújo Marina Rios, Ferreira Andrea Vidal, Silva Juliana Figueira, Cordeiro Marta do Nascimento, Borges Marcia Helena, Romano Silva Marco Aurélio, Gomez Marcus Vinicius, Castro Junior Célio Jose

机构信息

Department of Neurotransmitters, Santa Casa, Institute of Education and Research, Belo Horizonte, Brazil.

Radiobiology Department, Center for the Development of Nuclear Technology, National Commission of Nuclear Energy (CDTN/CNEN), Belo Horizonte, Brazil.

出版信息

Front Mol Biosci. 2022 Feb 4;8:770471. doi: 10.3389/fmolb.2021.770471. eCollection 2021.

DOI:10.3389/fmolb.2021.770471
PMID:35187065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8855152/
Abstract

Preclinical evidence suggests the potential of Ph1, a toxin obtained from the venom of spider , as a new analgesic drug. Molecular brain imaging techniques have afforded exciting opportunities to examine brain processes in clinical pain conditions. This paper aims to study the brain regions involved in the analgesic effects of Ph1 compared with Morphine, in a model of acute pain induced by formalin in Sprague Dawley rats. We used F-fluorodeoxyglucose as a metabolic radiotracer to perform brain imaging of rats pretreated with Ph1 or Morphine in a model of acute inflammatory pain caused by intraplantar injection of formalin. The rats' hind paw's formalin stimulation resulted in a brain metabolic increase at the bilateral motor cortex, visual cortex, somatosensory cortex, thalamus, and cingulate cortex.In rats treated with Ph1, selective inhibition of unilateral motor cortex and cingulate cortex was observed. Morphine treatment leads to small and selective inhibition at the bilateral amygdala striatum and accumbens. Our results indicate that the analgesic effect of Ph1 and Morphine possesses a differential profile of central processing in the pain state.

摘要

临床前证据表明,从蜘蛛毒液中提取的毒素Ph1有潜力成为一种新型镇痛药。分子脑成像技术为研究临床疼痛状态下的脑过程提供了令人兴奋的机会。本文旨在研究在福尔马林诱导的急性疼痛模型中,与吗啡相比,Ph1镇痛作用所涉及的脑区,实验对象为斯普拉格-道利大鼠。我们使用F-氟脱氧葡萄糖作为代谢放射性示踪剂,对在足底注射福尔马林引起的急性炎症性疼痛模型中预先用Ph1或吗啡处理的大鼠进行脑成像。大鼠后爪的福尔马林刺激导致双侧运动皮层、视觉皮层、体感皮层、丘脑和扣带回皮层的脑代谢增加。在用Ph1治疗的大鼠中,观察到单侧运动皮层和扣带回皮层的选择性抑制。吗啡治疗导致双侧杏仁核、纹状体和伏隔核出现轻微的选择性抑制。我们的结果表明,Ph1和吗啡的镇痛作用在疼痛状态下具有不同的中枢处理特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/9973ee506d71/fmolb-08-770471-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/1a1270be92ca/fmolb-08-770471-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/101bea66a543/fmolb-08-770471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/e2f2f15aec82/fmolb-08-770471-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/4d4e0bb58e91/fmolb-08-770471-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/9973ee506d71/fmolb-08-770471-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/1a1270be92ca/fmolb-08-770471-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/101bea66a543/fmolb-08-770471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/e2f2f15aec82/fmolb-08-770471-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/4d4e0bb58e91/fmolb-08-770471-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f206/8855152/9973ee506d71/fmolb-08-770471-g005.jpg

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本文引用的文献

1
The peptide Phα1β, from spider venom, acts as a TRPA1 channel antagonist with antinociceptive effects in mice.来自蜘蛛毒液的肽Phα1β在小鼠中作为一种具有抗伤害感受作用的TRPA1通道拮抗剂。
Br J Pharmacol. 2017 Jan;174(1):57-69. doi: 10.1111/bph.13652. Epub 2016 Nov 28.
2
Brain activations during pain: a neuroimaging meta-analysis of patients with pain and healthy controls.疼痛期间的大脑激活:对疼痛患者和健康对照者的神经影像学荟萃分析。
Pain. 2016 Jun;157(6):1279-1286. doi: 10.1097/j.pain.0000000000000517.
3
Effects of the calcium channel blockers Phα1β and ω-conotoxin MVIIA on capsaicin and acetic acid-induced visceral nociception in mice.
钙通道阻滞剂Phα1β和ω-芋螺毒素MVIIA对辣椒素和乙酸诱导的小鼠内脏痛觉的影响。
Pharmacol Biochem Behav. 2014 Nov;126:97-102. doi: 10.1016/j.pbb.2014.09.017. Epub 2014 Sep 28.
4
Gabapentin reverses central hypersensitivity and suppresses medial prefrontal cortical glucose metabolism in rats with neuropathic pain.加巴喷丁可逆转中枢性高敏反应,并抑制神经性疼痛大鼠内侧前额叶皮质的葡萄糖代谢。
Mol Pain. 2014 Sep 25;10:63. doi: 10.1186/1744-8069-10-63.
5
Phα1β, a peptide from the venom of the spider Phoneutria nigriventer shows antinociceptive effects after continuous infusion in a neuropathic pain model in rats.Phα1β是一种来自黑腹栉足蛛毒液的肽,在大鼠神经病理性疼痛模型中持续输注后显示出抗伤害感受作用。
Anesth Analg. 2014 Jul;119(1):196-202. doi: 10.1213/ANE.0000000000000249.
6
The effects of Phα1β, a spider toxin, calcium channel blocker, in a mouse fibromyalgia model.Phα1β 是一种蜘蛛毒素,也是一种钙通道阻滞剂,在小鼠纤维肌痛模型中的作用。
Toxicon. 2014 Apr;81:37-42. doi: 10.1016/j.toxicon.2014.01.015. Epub 2014 Jan 31.
7
Effect of ω-conotoxin MVIIA and Phα1β on paclitaxel-induced acute and chronic pain.ω-芋螺毒素 MVIIA 和 Phα1β 对紫杉醇诱导的急性和慢性疼痛的影响。
Pharmacol Biochem Behav. 2013 Dec;114-115:16-22. doi: 10.1016/j.pbb.2013.10.014. Epub 2013 Oct 19.
8
Spider peptide Phα1β induces analgesic effect in a model of cancer pain.蜘蛛肽 Phα1β 在癌症疼痛模型中诱导镇痛作用。
Cancer Sci. 2013 Sep;104(9):1226-30. doi: 10.1111/cas.12209. Epub 2013 Jun 25.
9
Phα1β toxin prevents capsaicin-induced nociceptive behavior and mechanical hypersensitivity without acting on TRPV1 channels.Phα1β 毒素可预防辣椒素诱导的痛觉行为和机械性超敏反应,而不作用于 TRPV1 通道。
Neuropharmacology. 2013 Aug;71:237-46. doi: 10.1016/j.neuropharm.2013.04.001. Epub 2013 Apr 15.
10
Antiallodynic effect and side effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer: comparison with ω-conotoxin MVIIA and morphine.Phα1β 对蜘蛛 Phoneutria nigriventer 的神经毒素的抗痛觉过敏作用和副作用:与 ω-conotoxin MVIIA 和吗啡的比较。
Toxicon. 2011 Dec 1;58(8):626-33. doi: 10.1016/j.toxicon.2011.09.008. Epub 2011 Sep 24.