Maegawa Hiroharu, Usami Nayuka, Kudo Chiho, Niwa Hitoshi
Department of Dental Anesthesiology, The University of Osaka Graduate School of Dentistry, Suita, Osaka, Japan.
PLoS One. 2025 May 14;20(5):e0323810. doi: 10.1371/journal.pone.0323810. eCollection 2025.
Calcitonin gene-related peptide (CGRP) and dopamine D2 receptor (D2 receptor) are associated with neuropathic pain. However, their relationship is not well understood. To better establish their relationship in trigeminal neuropathic pain, we examined male rats with infraorbital nerve (ION) ligation. Rats with ION ligation were administered CGRP or anti-CGRP antibody into the trigeminal ganglion (TG). The change in the head-withdrawal threshold was measured using von Frey filament. Immunohistochemical staining for phosphorylated extracellular signal-regulated kinase (pERK) was also performed in the trigeminal spinal subnucleus caudalis (Vc). CGRP was detected in the TG and Vc by immunohistochemical staining, and glial fibrillary acidic protein (GFAP) in the TG and dopamine D2 receptor in the Vc were detected in the same way. Antibody administration restored the head-withdrawal threshold to mechanical stimuli, which had decreased after ION ligation. Furthermore, the number of pERK-immunoreactive (-IR) neurons in the Vc, which increased following ION ligation, declined. The ratio of CGRP-IR TG neurons, large-sized CGRP-IR TG neurons, and TG neurons encircled with the GFAP-IR cells increased after ION ligation and decreased after antibody administration. Moreover, the immunoreactivity of CGRP and D2 receptor in the Vc increased after ION ligation and decreased after antibody administration. There were no significant differences in the head-withdrawal threshold, pERK-IR cell count, ratio of CGRP-IR TG neurons, ratio of size of CGRP-IR TG neurons, ratio of TG neurons encircled with GFAP-IR cells, and immunoreactivity of CGRP and D2 receptor in the Vc between the ION-ligated rats with and without CGRP. These findings suggest that the administration of an anti-CGRP antibody into the TG is involved in the suppression of trigeminal neuropathic pain and the D2 receptor expression in the Vc.
降钙素基因相关肽（CGRP）和多巴胺D2受体（D2受体）与神经性疼痛有关。然而，它们之间的关系尚未完全明确。为了更好地确定它们在三叉神经神经性疼痛中的关系，我们对眶下神经（ION）结扎的雄性大鼠进行了研究。将CGRP或抗CGRP抗体注射到ION结扎大鼠的三叉神经节（TG）中。使用von Frey细丝测量缩头阈值的变化。还在三叉神经脊髓尾侧亚核（Vc）中进行了磷酸化细胞外信号调节激酶（pERK）的免疫组织化学染色。通过免疫组织化学染色在TG和Vc中检测到CGRP，以同样的方式在TG中检测到胶质纤维酸性蛋白（GFAP），在Vc中检测到多巴胺D2受体。注射抗体后，缩头阈值恢复到ION结扎后降低的机械刺激阈值水平。此外，ION结扎后增加的Vc中pERK免疫反应性（-IR）神经元数量减少。ION结扎后，CGRP-IR TG神经元、大型CGRP-IR TG神经元以及被GFAP-IR细胞环绕的TG神经元的比例增加，注射抗体后降低。此外，ION结扎后Vc中CGRP和D2受体的免疫反应性增加，注射抗体后降低。在注射和未注射CGRP的ION结扎大鼠之间，缩头阈值、pERK-IR细胞计数、CGRP-IR TG神经元比例、CGRP-IR TG神经元大小比例、被GFAP-IR细胞环绕的TG神经元比例以及Vc中CGRP和D2受体的免疫反应性均无显著差异。这些发现表明，向TG注射抗CGRP抗体参与了对三叉神经神经性疼痛的抑制以及Vc中D2受体的表达。
