Département de Pharmacologie-Physiologie, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Institut de Pharmacologie de Sherbrooke, Centre de Recherche du CHUS, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Eur J Neurosci. 2022 Aug;56(3):4031-4044. doi: 10.1111/ejn.15733. Epub 2022 Jun 14.
Primary afferents are responsible for transmitting signals produced by noxious stimuli from the periphery to the spinal cord. Mu and delta opioid receptors (MOP and DOP) have analgesic properties and are highly expressed in dorsal root ganglia (DRG) neurons. In humans, spinal DOP is almost exclusively located on central terminals of DRG neurons, whereas in rodents, it is expressed both on presynaptic terminals and spinal neurons. In this study, we aimed to assess the distribution of MOP and DOP in the DRGs of mice and rats. Using in situ hybridization and immunofluorescence, we visualized MOP and DOP mRNA together with various neuronal markers. In rats and mice, we show that both receptors are expressed, albeit to different extents, in all types of neurons, namely, large and medium myelinated neurons (NF200-positive), small nonpeptidergic (IB4- or P2X3R-positive) and peptidergic C fibres (Tac1-positive). Overall, DOP mRNA was found to be mainly expressed in large and medium myelinated neurons, whereas MOP mRNA was mainly found in C fibres. The distribution of MOP and DOP, however, slightly differs between rats and mice, with a higher proportion of small nonpeptidergic C fibres expressing DOP mRNA in mice than in rats. We further found that neither morphine nor inflammation affected the distribution of the receptor mRNA. Because of their location, our results confirm that MOP and DOP have the potential to alleviate similar types of pain and that this effect could slightly differ between species.
初级传入纤维负责将来自外周的有害刺激产生的信号传递到脊髓。μ 和 δ 阿片受体(MOP 和 DOP)具有镇痛特性,在背根神经节(DRG)神经元中高度表达。在人类中,脊髓 DOP 几乎仅位于 DRG 神经元的中枢末端,而在啮齿动物中,它既表达在突触前末端,也表达在脊髓神经元上。在这项研究中,我们旨在评估 MOP 和 DOP 在小鼠和大鼠 DRG 中的分布。通过原位杂交和免疫荧光,我们可视化了 MOP 和 DOP mRNA 以及各种神经元标志物。在大鼠和小鼠中,我们表明两种受体都在所有类型的神经元中表达,尽管程度不同,即大中和小有髓神经元(NF200 阳性)、小非肽能(IB4 或 P2X3R 阳性)和肽能 C 纤维(Tac1 阳性)。总的来说,DOP mRNA 主要在大中和小有髓神经元中表达,而 MOP mRNA 主要在 C 纤维中表达。然而,MOP 和 DOP 的分布在大鼠和小鼠之间略有不同,与大鼠相比,小鼠中小非肽能 C 纤维表达 DOP mRNA 的比例更高。我们进一步发现,吗啡和炎症都不会影响受体 mRNA 的分布。由于其位置,我们的结果证实 MOP 和 DOP 具有缓解类似类型疼痛的潜力,并且这种作用在物种之间可能略有不同。