Effects of somatostatin, a somatostatin agonist, and an antagonist, on a putative migraine trigger pathway

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2023-12-12 DOI:10.1016/j.npep.2023.102399

Geoffrey A. Lambert , Alessandro S. Zagami

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引用次数: 0

Abstract

Objective

To determine whether somatostatin (SST) could be a cortico-brainstem neurotransmitter involved in producing the headache of migraine.

Background

There is evidence to support the idea that a cortico-brainstem-trigeminal nucleus neuraxis might be responsible for producing migraine headache; we have suggested that SST may be one of the neurotransmitters involved.

Methods

Rats were anesthetised and prepared for recording neurons in either the periaqueductal gray matter (PAG) or nucleus raphe magnus (NRM), as well as the trigeminal nucleus caudalis (TNC). The dura mater and facial skin were stimulated electrically or mechanically. SST, the SST agonist L054264 and the SST antagonist CYN54806 were injected intravenously, by microinjection, or by iontophoresis into the PAG or NRM. Cortical neuronal activity was provoked by cortical spreading depression (CSD) or light flash (LF) and was monitored by recording cortical blood flow (CBF).

Results

Intravenous injection of SST: (a) selectively decreased the responses of TNC neurons to stimulation of the dura, but not skin, for up to 5 h; (b) decreased the ongoing discharge rate of TNC neurons while simultaneously increasing the discharge rate of neurons in either brainstem nucleus and; (c) prevented, or reversed, the effect of CSD and LF on brainstem and trigeminal neuron discharge rates. CSD and LF decreased the discharge rate of neurons in both brainstem nuclei and increased the discharge rate of TNC neurons. These effects were reversed by L054264 and mimicked by CYN54806. Injections of L054264 into the PAG or NRM reduced the response of TNC neurons to dural stimulation and skin stimulation differentially, depending on the nucleus injected. Injections of CYN54806 into either brainstem nucleus potentiated the responses of TNC neurons to dural and skin stimulation, but without a marked differential effect.

Conclusions

These results imply that SST could be a neurotransmitter in a pathway responsible for migraine pain.

查看原文本刊更多论文

体生长抑素、体生长抑素激动剂和拮抗剂对假定偏头痛触发途径的影响

背景有证据表明，皮质-脑干-三叉神经核神经轴可能是产生偏头痛的原因；我们认为，体生长抑素（SST）可能是其中的一种神经递质。方法对大鼠进行麻醉，准备记录其uctal周围灰质（PAG）或剑突大核（NRM）以及三叉神经尾核（TNC）的神经元。硬脑膜和面部皮肤受到电刺激或机械刺激。将 SST、SST 激动剂 L054264 和 SST 拮抗剂 CYN54806 通过静脉注射、显微注射或离子注入 PAG 或 NRM。皮质展延抑制（CSD）或光闪（LF）诱发皮质神经元活动，并通过记录皮质血流（CBF）进行监测。结果静脉注射 SST：(a) 选择性地降低 TNC 神经元对硬脑膜刺激的反应，但不降低皮肤刺激的反应，持续时间长达 5 小时；(b) 降低 TNC 神经元的持续放电率，同时提高任一脑干核神经元的放电率；(c) 阻止或逆转 CSD 和 LF 对脑干和三叉神经元放电率的影响。CSD 和 LF 降低了两个脑干核中神经元的放电率，增加了 TNC 神经元的放电率。这些效应被 L054264 逆转，并被 CYN54806 模拟。向 PAG 或 NRM 注射 L054264 会降低 TNC 神经元对硬脑膜刺激和皮肤刺激的反应，这取决于注射的神经核。向任一脑干核注射 CYN54806 都会增强 TNC 神经元对硬脑膜刺激和皮肤刺激的反应，但没有明显的差异效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.