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.

中文翻译：

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生长抑素、生长抑素激动剂和拮抗剂对假定的偏头痛触发途径的影响

客观的

确定生长抑素 (SST) 是否可能是一种皮质脑干神经递质，与偏头痛的产生有关。

背景

有证据支持皮质-脑干-三叉神经核神经轴可能导致偏头痛的观点。我们认为 SST 可能是其中涉及的神经递质之一。

方法

将大鼠麻醉并准备记录导水管周围灰质（PAG）或中缝大核（NRM）以及三叉神经尾核（TNC）中的神经元。硬脑膜和面部皮肤受到电或机械刺激。通过显微注射或离子电渗疗法将SST、SST激动剂L054264和SST拮抗剂CYN54806静脉注射到PAG或NRM中。皮质神经元活动由皮质扩散抑制（CSD）或闪光（LF）引起，并通过记录皮质血流量（CBF）进行监测。

结果

静脉注射 SST：(a) 选择性降低 TNC 神经元对硬脑膜（而非皮肤）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，同时增加任一脑干核中神经元的放电率； (c) 预防或逆转 CSD 和 LF 对脑干和三叉神经元放电率的影响。 CSD和LF降低了两个脑干核团神经元的放电率，增加了TNC神经元的放电率。这些效应被 L054264 逆转并被 CYN54806 模仿。将 L054264 注射到 PAG 或 NRM 中会不同程度地降低 TNC 神经元对硬脑膜刺激和皮肤刺激的反应，具体取决于注射的细胞核。将 CYN54806 注射到任一脑干核中都会增强 TNC 神经元对硬脑膜和皮肤刺激的反应，但没有明显的差异效应。

结论

这些结果表明，SST 可能是导致偏头痛的通路中的一种神经递质。