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内源性催产素在大鼠中发挥抗伤害感受和抗炎作用。

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats.

机构信息

Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

出版信息

Commun Biol. 2022 Sep 5;5(1):907. doi: 10.1038/s42003-022-03879-8.

DOI:10.1038/s42003-022-03879-8
PMID:36064593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9445084/
Abstract

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.

摘要

催产素参与疼痛传递，但其详细机制尚不完全清楚。在这里，我们构建了一种转基因大鼠品系，该品系在催产素神经元中表达人毒蕈碱型乙酰胆碱受体（hM3Dq）和 mCherry。我们报告说，我们的催产素-hM3Dq-mCherry 大鼠用氯氮平-N-氧化物（CNO）处理仅能特异性地激活室旁核和视上核内的催产素神经元，导致蓝斑核（LC）和中缝背核（DR）神经元的激活，并导致 L5 脊髓背角 GABA 能神经元的差异基因表达。在实验性疼痛模型中，痛觉过敏明显加重，而 CNO 注射后则显著减轻。催产素受体拮抗剂共同处理可消除 CNO 的镇痛作用。内源性催产素还通过激活下丘脑-垂体-肾上腺轴发挥抗炎作用。此外，发现肥大细胞脱颗粒的抑制参与了该反应。总之，我们的研究结果表明，催产素可能通过神经元和体液途径发挥抗伤害感受和抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/445e17a01c0a/42003_2022_3879_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/85243c307192/42003_2022_3879_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/5646a4a035aa/42003_2022_3879_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/c06a9872ecf7/42003_2022_3879_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/1a498edc4750/42003_2022_3879_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/5de4206d6cf7/42003_2022_3879_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/c9535618c214/42003_2022_3879_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bf/9445084/445e17a01c0a/42003_2022_3879_Fig10_HTML.jpg

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