Instituto De Investigação e Inovação Em Saúde, Universidade Do Porto, Porto, Portugal; Neuronal Networks Group, Instituto De Biologia Molecular e Celular (IBMC), Universidade Do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
MTA-DE Neuroscience Research Group, Debrecen, Hungary; Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Prog Neurobiol. 2020 May;188:101786. doi: 10.1016/j.pneurobio.2020.101786. Epub 2020 Mar 12.
Presynaptic inhibition of primary afferent terminals is a powerful mechanism for controlling sensory information flow into the spinal cord. Lamina I is the major spinal nociceptive projecting area and monosynaptic input from C-fibers to this region represents a direct pathway for transmitting pain signals to supraspinal centers. Here we used an isolated spinal cord preparation to show that this pathway is under control of the afferent-driven GABAergic presynaptic inhibition. Presynaptic inhibition of C-fiber input to lamina I projection and local-circuit neurons is mediated by recruitment of Aβ-, Aδ- and C-afferents. C-fiber-driven inhibition of C-fibers functions as a feedforward mechanism, by which the homotypic afferents control sensory information flow into the spinal cord and regulate degree of the primary nociceptive afferent activation needed to excite the second order neurons. The presynaptic inhibition of C-fiber input to lamina I neurons may be mediated by both synaptic and non-synaptic mechanisms, and its occurrence and extent are quite heterogeneous. This heterogeneity is likely to be reflective of involvement of lamina I neurons in diverse circuitries processing specific modalities of sensory information in the superficial dorsal horn. Thus, our results implicate both low- and high-threshold afferents in the modulation of C-fiber input into the spinal cord.
初级传入末梢的突触前抑制是控制感觉信息传入脊髓的一种强大机制。I 层是主要的脊髓伤害性投射区，C 纤维到该区域的单突触传入代表了将疼痛信号传递到脊髓上中枢的直接途径。在这里，我们使用分离的脊髓标本表明，该途径受到传入驱动的 GABA 能突触前抑制的控制。C 纤维输入到 I 层投射和局部回路神经元的突触前抑制是通过募集 Aβ、Aδ 和 C 传入纤维介导的。C 纤维驱动的 C 纤维抑制作为一种前馈机制，通过该机制同型传入纤维控制感觉信息传入脊髓，并调节激发第二级神经元所需的初级伤害性传入激活的程度。C 纤维输入到 I 层神经元的突触前抑制可能通过突触和非突触机制介导，其发生和程度具有很大的异质性。这种异质性可能反映了 I 层神经元参与了在背角浅层处理特定感觉信息模式的不同回路。因此，我们的结果表明，低阈值和高阈值传入纤维都参与了脊髓中 C 纤维传入的调制。
