Hitomi Suzuro, Okada-Ogawa Akiko, Sato Yuka, Shibuta-Suzuki Ikuko, Shinoda Masamichi, Imamura Yoshiki, Ono Kentaro, Iwata Koichi
Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
Department of Oral Diagnostic Science, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Oral Health Science, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Neurosci Lett. 2017 Apr 24;647:14-19. doi: 10.1016/j.neulet.2017.03.023. Epub 2017 Mar 18.
Although it is well known that migraine pain is enhanced by photic stimulation of the eye, the mechanisms underlying this response are not yet understood. Noxious stimulation to the dura is known to activate trigeminal spinal subnucleus caudalis and upper cervical spinal cord (Vc/C1) neurons, causing migraine pain. Intense photic stimulation to the eye is also known to activate certain Vc/C1 neurons, thus increasing migraine pain. In this study, we hypothesized that Vc/C1 neurons receiving noxious dural input would be further activated by intense photic stimulation, resulting in the enhancement of migraine pain. However, mechanisms underlying the interactions between dural and photic sensory information in Vc/C1 neurons is unknown. To evaluate the above hypothesis, we studied phosphorylated extracellular signal-regulated kinase (pERK) -immunoreactive (IR) cells in Vc/C1 in dural mustard oil (DMO)-administrated rats. The change in neuronal excitability of Vc/C1 nociceptive neurons receiving input from the dura in DMO rats was examined and tested if those neurons were modulated by intense flush light stimulation. There were many pERK-IR cells in the lateral portion of Vc/C1 after MO administration to the dura. Flashlight presentation to the eye in DMO rats caused an enhancement of ERK phosphorylation in Vc/C1 neurons and pERK-IR cells were significantly suppressed after intracisternal administration of MEK1 inhibitor PD98059. Dura-light sensitive (DL) neurons were recorded in the lateral portion of Vc/C1 and photic responses of DL neurons were significantly enhanced following dural MO administration. These findings indicate that DL Vc/C1 neurons in DMO rats intensified their responses to intense photic stimulation and that ERK phosphorylation in Vc/C1 neurons receiving noxious dural input increased with intense photic stimulation, suggesting that Vc/C1 nociceptive neurons are involved in the enhancement of dural nociception associated with intense light stimulation.
虽然众所周知，眼部的光刺激会加剧偏头痛疼痛，但这种反应背后的机制尚不清楚。已知对硬脑膜的伤害性刺激会激活三叉神经脊髓尾侧亚核和颈髓上段（Vc/C1）神经元，从而引发偏头痛疼痛。对眼睛的强光刺激也已知会激活某些Vc/C1神经元，进而加剧偏头痛疼痛。在本研究中，我们假设接受伤害性硬脑膜输入的Vc/C1神经元会因强光刺激而进一步激活，导致偏头痛疼痛加剧。然而，Vc/C1神经元中硬脑膜和光感觉信息之间相互作用的机制尚不清楚。为了评估上述假设，我们研究了在硬脑膜给予芥子油（DMO）的大鼠中，Vc/C1中磷酸化细胞外信号调节激酶（pERK）免疫反应性（IR）细胞。检查了DMO大鼠中接受来自硬脑膜输入的Vc/C1伤害性神经元的神经元兴奋性变化，并测试了这些神经元是否受到强光刺激的调节。向硬脑膜给予MO后，Vc/C1外侧部分有许多pERK-IR细胞。在DMO大鼠中，向眼睛照射手电筒会导致Vc/C1神经元中ERK磷酸化增强，而在脑池内给予MEK1抑制剂PD98059后，pERK-IR细胞明显受到抑制。在Vc/C1外侧部分记录到了硬脑膜-光敏感（DL）神经元，硬脑膜给予MO后，DL神经元的光反应明显增强。这些发现表明，DMO大鼠中的DL Vc/C1神经元增强了对强光刺激的反应，并且接受伤害性硬脑膜输入的Vc/C1神经元中的ERK磷酸化随着强光刺激而增加，这表明Vc/C1伤害性神经元参与了与强光刺激相关的硬脑膜伤害感受的增强。
