Ma Wenhui, Dickie Allen, Polgár Erika, Yadav Mansi, Quillet Raphaelle, Gutierrez-Mecinas Maria, Bell Andrew M, Todd Andrew
School of Psychology and Neuroscience, Sir James Black Building, University of Glasgow, Glasgow, G12 8QQ, UK.
School of Biodiversity, One Health and Veterinary Medicine, University of Glasgow, G61 1QH, UK.
Mol Pain. 2025 May 7:17448069251342409. doi: 10.1177/17448069251342409.
Anterolateral system (ALS) projection neurons underlie perception of pain, itch and skin temperature. These cells are heterogeneous, and there have therefore been many attempts to define functional populations. A recent study identified two classes of ALS neuron in mouse superficial dorsal horn (SDH) based on expression of the G protein-coupled receptors Tacr1 or Gpr83. It was reported that cells expressing these receptors formed largely non-overlapping populations, and that ~60% of ALS cells in SDH expressed Tacr1. An additional finding was that while Tacr1- and Gpr83-expressing ALS cells projected to several brain nuclei, their axons did not reach the ventral posterolateral (VPL) thalamic nucleus, which is reciprocally connected to the primary somatosensory cortex. These results were surprising, because we had reported that ~90% of SDH ALS neurons in the mouse possess the neurokinin 1 receptor (NK1r), which is encoded by Tacr1, and in addition the VPL is thought to receive input from lamina I ALS cells. Here we use retrograde and anterograde labelling in Tacr1CreERT2 and Gpr83CreERT2 mice to reinvestigate the expression of the receptors by ALS neurons and to reassess their projection patterns. We find that ~90% of ALS neurons in SDH express Tacr1, with 40-50% expressing Gpr83. We also show that axons of both Tacr1- and Gpr83-expressing ALS neurons reach the VPL. These results suggest that ALS neurons in the SDH that express these GPCRs show considerable overlap, and that they are likely to contribute to the sensory-discriminative dimension of pain through their projections to VPL.
前外侧系统（ALS）投射神经元是疼痛、瘙痒和皮肤温度感知的基础。这些细胞具有异质性，因此人们进行了许多尝试来定义功能群体。最近的一项研究基于G蛋白偶联受体Tacr1或Gpr83的表达，在小鼠浅表背角（SDH）中鉴定出两类ALS神经元。据报道，表达这些受体的细胞形成了 largely 不重叠的群体，并且SDH中约60%的ALS细胞表达Tacr1。另一个发现是，虽然表达Tacr1和Gpr83的ALS细胞投射到几个脑核，但它们的轴突并未到达与初级体感皮层相互连接的腹后外侧（VPL）丘脑核。这些结果令人惊讶，因为我们曾报道小鼠SDH中约90%的ALS神经元拥有由Tacr1编码的神经激肽1受体（NK1r），此外，VPL被认为接收来自I层ALS细胞的输入。在这里，我们在Tacr1CreERT2和Gpr83CreERT2小鼠中使用逆行和顺行标记，以重新研究ALS神经元中这些受体的表达，并重新评估它们的投射模式。我们发现SDH中约90%的ALS神经元表达Tacr1，40 - 50%表达Gpr83。我们还表明，表达Tacr1和Gpr83的ALS神经元的轴突都到达了VPL。这些结果表明，SDH中表达这些GPCR的ALS神经元表现出相当大的重叠，并且它们可能通过投射到VPL对疼痛的感觉辨别维度做出贡献。
