背景:上颈背根神经节(DRG)对于传递与头颈后部相关的感觉信息很重要,导致头部疼痛。降钙素受体(CTR)为基础的受体,如胰淀素1(AMY1)受体,和配体,降钙素基因相关肽(CGRP)和胰淀素,与偏头痛和疼痛有关.然而,该系统对涉及宫颈DRG的伤害性感受的贡献尚不清楚.因此,这项研究旨在确定CTR的相对分布,CGRP,和胰淀素在上子宫颈DRG中。
方法:CTR,CGRP,在雄性和雌性小鼠的C1/2DRG中,相对于神经标记进行了胰淀素免疫荧光检查,老鼠,和人类案例。通过RNA荧光原位杂交检查大鼠DRG中胰淀素mRNA的分布来支持免疫荧光。
结果:在神经元细胞和纤维中观察到淀粉样蛋白免疫荧光。还检测到胰淀素mRNA(Iapp)。在19%(小鼠)中观察到胰淀素和CGRP共表达,17%(鼠),和36%(人类)的DRG神经元在彼此不同的囊泡样神经元点中。CTR免疫反应性存在于DRG神经元中,和两种肽在原代DRG细胞培养物中产生受体信号传导。CTR阳性神经元经常共表达胰淀素和/或CGRP(66%大鼠;84%人),有一些性别差异。
结论:胰淀素和CGRP都可能是上宫颈DRG中基于CTR的受体的局部肽激动剂,可能通过自分泌和/或旁分泌信号机制来调节神经元功能。胰淀素及其受体可以代表新的疼痛靶标。
BACKGROUND: The upper cervical dorsal root ganglia (DRG) are important for the transmission of sensory information associated with the back of the head and neck, contributing to head pain. Calcitonin receptor (CTR)-based receptors, such as the amylin 1 (AMY1) receptor, and ligands, calcitonin gene-related peptide (CGRP) and amylin, have been linked to migraine and pain. However, the contribution of this system to nociception involving the cervical DRG is unclear. Therefore, this study aimed to determine the relative distribution of the CTR, CGRP, and amylin in upper cervical DRG.
METHODS: CTR, CGRP, and amylin immunofluorescence was examined relative to neural markers in C1/2 DRG from male and female mice, rats, and human cases. Immunofluorescence was supported by RNA-fluorescence in situ hybridization examining amylin mRNA distribution in rat DRG.
RESULTS: Amylin immunofluorescence was observed in neuronal soma and fibres. Amylin mRNA (Iapp) was also detected. Amylin and CGRP co-expression was observed in 19% (mouse), 17% (rat), and 36% (human) of DRG neurons in distinct vesicle-like neuronal puncta from one another. CTR immunoreactivity was present in DRG neurons, and both peptides produced receptor signalling in primary DRG cell cultures. CTR-positive neurons frequently co-expressed amylin and/or CGRP (66% rat; 84% human), with some sex differences.
CONCLUSIONS: Amylin and CGRP could both be local peptide agonists for CTR-based receptors in upper cervical DRG, potentially acting through autocrine and/or paracrine signalling mechanisms to modulate neuron function. Amylin and its receptors could represent novel pain targets.