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Cell. Neurosci."],"abstract":"<jats:p>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 A\u03b4- and C-afferents. Unmyelinated C-fibers were selectively activated by electrical stimuli of negative polarity that induced an anodal block of myelinated A\u03b2\/\u03b4-fibers. Combining this approach with the patch-clamp recording in an <jats:italic>ex vivo<\/jats:italic> spinal cord preparation, we found that attenuation of the AD-PI by the anodal block of A\u03b2\/\u03b4-fibers resulted in the appearance of new mono- and polysynaptic C-fiber-mediated excitatory postsynaptic current (EPSC) components. Such homosegmental A\u03b2\/\u03b4-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 A\u03b4- 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 A\u03b4- and C-fiber inputs, as well as some direct L5 A\u03b2-fiber inputs. Moreover, the C-AD-PI was found to control the spike discharge in spinal neurons. Given that the homosegmental A\u03b2\/\u03b4-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.<\/jats:p>","DOI":"10.3389\/fncel.2022.1029799","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T05:25:10Z","timestamp":1673414710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Elucidating afferent-driven presynaptic inhibition of primary afferent input to spinal laminae I and X"],"prefix":"10.3389","volume":"16","author":[{"given":"Volodymyr","family":"Krotov","sequence":"first","affiliation":[]},{"given":"Kirill","family":"Agashkov","sequence":"additional","affiliation":[]},{"given":"Sergii","family":"Romanenko","sequence":"additional","affiliation":[]},{"given":"Oleh","family":"Halaidych","sequence":"additional","affiliation":[]},{"given":"Yaroslav","family":"Andrianov","sequence":"additional","affiliation":[]},{"given":"Boris V.","family":"Safronov","sequence":"additional","affiliation":[]},{"given":"Pavel","family":"Belan","sequence":"additional","affiliation":[]},{"given":"Nana","family":"Voitenko","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1002\/CNE.903290405","article-title":"Ultrastructural morphology, synaptic relationships, and CGRP immunoreactivity of physiologically identified C-fiber terminals in the monkey spinal cord.","volume":"329","author":"Alvarez","year":"1993","journal-title":"J. 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