Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Suita, Osaka, 565-0871, Japan.
Biochem Biophys Res Commun. 2022 Jul 23;614:78-84. doi: 10.1016/j.bbrc.2022.05.015. Epub 2022 May 10.
A dopamine D2 receptor (D2R) agonist and an anti-calcitonin gene-related peptide (CGRP) antibody were separately reported to reduce neuropathic pain. To further attenuate neuropathic pain, co-administration of a D2R agonist and an anti-CGRP antibody was performed in a rat with the infraorbital nerve (ION) ligation. However, this co-administration showed no further attenuation of mechanical hypersensitivity compared to the administration of anti-CGRP antibody alone. Our results also revealed that D2R immunoreactivity in the trigeminal spinal subnucleus caudalis (Vc) increased following the nerve ligation and decreased following administration of an anti-CGRP antibody. The ratio of immunoreactive neurons of phosphorylated cyclic adenosine monophosphate-response-element-binding protein in the Vc also increased following nerve ligation and decreased with the anti-CGRP antibody. Our results suggest that a decrease in D2R immunoreactivity reduces the effect of a D2R agonist, and transcription of D2R is activated following the ION ligation and suppressed by treatment with an anti-CGRP antibody.
一种多巴胺 D2 受体(D2R)激动剂和一种抗降钙素基因相关肽(CGRP)抗体分别被报道可减轻神经性疼痛。为了进一步减轻神经性疼痛,在眶下神经(ION)结扎的大鼠中,分别给予 D2R 激动剂和抗 CGRP 抗体。然而,与单独给予抗 CGRP 抗体相比,这种联合给药并未进一步减轻机械性过敏。我们的结果还表明,神经结扎后三叉神经脊束核尾侧亚核(Vc)中的 D2R 免疫反应性增加,给予抗 CGRP 抗体后则减少。Vc 中磷酸化环腺苷酸反应元件结合蛋白免疫反应性神经元的比率也随着神经结扎而增加,并且随着抗 CGRP 抗体的给药而减少。我们的结果表明,D2R 免疫反应性的降低会降低 D2R 激动剂的作用,而 D2R 的转录在 ION 结扎后被激活,并被抗 CGRP 抗体抑制。