Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China; Department of Neurophysiology, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
Department of Neurophysiology, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany; Deptartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
Neurosci Lett. 2023 Nov 1;816:137509. doi: 10.1016/j.neulet.2023.137509. Epub 2023 Oct 5.
Latent spinal sensitization is one key mechanism developing at the early stage of chronic low back pain (LBP). TRPM3-mediated calcium transients of dorsal root ganglia (DRG) neurons are considered critical presynaptic signals involved in this latent sensitization. However, postsynaptic consequences in input laminae of the spinal cord have not been addressed so far. Here, by electrophysiological recordings in acute spinal cord slices from adult rats, we show that perfusion of the TRPM3 agonist pregnenolone sulfate (PregS) induced a significant increase in the frequency but not amplitude of spontaneous postsynaptic currents in lamina I and II neurons. This frequency increase started slowly during PregS perfusion but was reversible following washout. This result is consistent with a presynaptic action of the neurosteroid PregS, indicating the presynaptic expression of functional TRPM3 in the superficial dorsal horn of adult rats. Thus, PregS-induced TRPM3 activation enhances spinal synaptic strength, implying a mediating role of TRPM3 between neuroendocrine and nociceptive signaling, which might as well exist in chronic LBP primed by chronic stress that promotes the biosynthesis of PregS.
潜伏性脊髓敏化是慢性腰痛（LBP）早期发展的一个关键机制。背根神经节（DRG）神经元中 TRPM3 介导的钙瞬变被认为是涉及这种潜伏性敏化的关键突触前信号。然而，迄今为止，脊髓输入层中的突触后后果尚未得到解决。在这里，我们通过对成年大鼠急性脊髓切片的电生理记录显示，TRPM3 激动剂孕烯醇酮硫酸盐（PregS）的灌流导致 I 层和 II 层神经元的自发性突触后电流频率而非幅度显著增加。这种频率增加在 PregS 灌流期间缓慢开始，但在冲洗后可逆转。这一结果与神经甾体 PregS 的突触前作用一致，表明成年大鼠背角浅层中功能性 TRPM3 的突触前表达。因此，PregS 诱导的 TRPM3 激活增强了脊髓突触强度，这表明 TRPM3 在神经内分泌和伤害性信号之间存在介导作用，这种作用在慢性应激引发的慢性腰痛中可能存在，慢性应激会促进 PregS 的生物合成。
