Elucidating afferent-driven presynaptic inhibition of primary afferent input to spinal laminae I and X

Volodymyr Krotov; Kirill Agashkov; Sergii Romanenko; Oleh Halaidych; Yaroslav Andrianov; Boris V Safronov; Pavel Belan; Nana Voitenko

doi:10.3389/fncel.2022.1029799

Elucidating afferent-driven presynaptic inhibition of primary afferent input to spinal laminae I and X

Front Cell Neurosci. 2023 Jan 11:16:1029799. doi: 10.3389/fncel.2022.1029799. eCollection 2022.

Authors

Volodymyr Krotov^{1

2}, Kirill Agashkov¹, Sergii Romanenko¹, Oleh Halaidych¹, Yaroslav Andrianov¹, Boris V Safronov^{3

4}, Pavel Belan^{2

5}, Nana Voitenko^{1

5

6}

Affiliations

¹ Department of Sensory Signaling, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
² Department of Molecular Biophysics, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
³ i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
⁴ Neuronal Networks Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
⁵ Department of Biomedicine and Neuroscience, Kyiv Academic University, Kyiv, Ukraine.
⁶ Dobrobut Academy Medical School, Kyiv, Ukraine.

Abstract

Although spinal processing of sensory information greatly relies on afferent-driven (AD) presynaptic inhibition (PI), our knowledge about how it shapes peripheral input to different types of nociceptive neurons remains insufficient. Here we examined the AD-PI of primary afferent input to spinal neurons in the marginal layer, lamina I, and the layer surrounding the central canal, lamina X; two nociceptive-processing regions with similar patterns of direct supply by Aδ- and C-afferents. Unmyelinated C-fibers were selectively activated by electrical stimuli of negative polarity that induced an anodal block of myelinated Aβ/δ-fibers. Combining this approach with the patch-clamp recording in an ex vivo spinal cord preparation, we found that attenuation of the AD-PI by the anodal block of Aβ/δ-fibers resulted in the appearance of new mono- and polysynaptic C-fiber-mediated excitatory postsynaptic current (EPSC) components. Such homosegmental Aβ/δ-AD-PI affected neurons in the segment of the dorsal root entrance as well as in the adjacent rostral segment. In their turn, C-fibers from the L5 dorsal root induced heterosegmental AD-PI of the inputs from the L4 Aδ- and C-afferents to the neurons in the L4 segment. The heterosegmental C-AD-PI was reciprocal since the L4 C-afferents inhibited the L5 Aδ- and C-fiber inputs, as well as some direct L5 Aβ-fiber inputs. Moreover, the C-AD-PI was found to control the spike discharge in spinal neurons. Given that the homosegmental Aβ/δ-AD-PI and heterosegmental C-AD-PI affected a substantial percentage of lamina I and X neurons, we suggest that these basic mechanisms are important for shaping primary afferent input to the neurons in the spinal nociceptive-processing network.

Keywords: A-fibers; C-fibers; lamina I; lamina X; presynaptic inhibition; primary afferents; spinal cord.

Grants and funding

This work was supported by the NASU Stipend for Young Scientists (VK), grant of the NAS of Ukraine to research laboratories/groups of young scientists of the NAS of Ukraine for conducting research in priority areas of the development of science and technology in 2022–2023 (OH), PTDC/NEU-NMC/1259/2014 POCI-01-0145-FEDER-016588 and POCI-01-0145-FEDER-016385 (BVS), 1R01NS113189-01 (PB and NV), and NASU grant 0118U007345 (PB).