Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan.
Department of Oral Surgery, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan.
Sci Rep. 2022 Sep 7;12(1):15190. doi: 10.1038/s41598-022-19562-1.
Recent noninvasive neuroimaging technology has revealed that spatiotemporal patterns of cortical spontaneous activity observed in chronic pain patients are different from those in healthy subjects, suggesting that the spontaneous cortical activity plays a key role in the induction and/or maintenance of chronic pain. However, the mechanisms of the spontaneously emerging activities supposed to be induced by nociceptive inputs remain to be established. In the present study, we investigated spontaneous cortical activities in sessions before and after electrical stimulation of the periodontal ligament (PDL) by applying wide-field and two-photon calcium imaging to anesthetized GCaMP6s transgenic mice. First, we identified the sequential cortical activation patterns from the primary somatosensory and secondary somatosensory cortices to the insular cortex (IC) by PDL stimulation. We, then found that spontaneous IC activities that exhibited a similar spatiotemporal cortical pattern to evoked activities by PDL stimulation increased in the session after repetitive PDL stimulation. At the single-cell level, repetitive PDL stimulation augmented the synchronous neuronal activity. These results suggest that cortical plasticity induced by the repetitive stimulation leads to the frequent PDL stimulation-evoked-like spontaneous IC activation. This nociception-induced spontaneous activity in IC may be a part of mechanisms that induces chronic pain.
最近的非侵入性神经影像学技术揭示，慢性疼痛患者的皮质自发性活动的时空模式与健康受试者不同，这表明自发性皮质活动在慢性疼痛的诱导和/或维持中起着关键作用。然而，由伤害性输入引起的自发性出现的活动的机制仍有待确定。在本研究中，我们通过对 GCaMP6s 转基因小鼠进行宽场和双光子钙成像，研究了牙周膜（PDL）电刺激前后的自发性皮质活动。首先，我们通过 PDL 刺激从初级体感和次级体感皮层到岛叶皮层（IC）确定了顺序皮质激活模式。然后，我们发现，在重复 PDL 刺激后的会话中，表现出与 PDL 刺激引起的活动相似的时空皮质模式的自发性 IC 活动增加。在单细胞水平上，重复 PDL 刺激增强了同步神经元活动。这些结果表明，重复刺激引起的皮质可塑性导致了频繁的 PDL 刺激样自发性 IC 激活。IC 中的这种伤害感受诱导的自发性活动可能是引起慢性疼痛的机制的一部分。
