{"doi":"10.3389/fncel.2022.1029799","title":"Elucidating afferent-driven presynaptic inhibition of primary afferent input to spinal laminae I and X","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.","journal":"Frontiers in Cellular Neuroscience","year":2023,"id":365099,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1097827,"name":"Kirill Agashkov","orcid":"0000-0002-3975-8789","position":1,"is_corresponding":false},{"id":1097828,"name":"Sergii Romanenko","orcid":"0000-0002-3181-0909","position":2,"is_corresponding":false},{"id":1121072,"name":"Oleh Halaidych","orcid":null,"position":3,"is_corresponding":false},{"id":1120618,"name":"Yaroslav Andrianov","orcid":"0000-0001-6954-0767","position":4,"is_corresponding":false},{"id":1120619,"name":"Boris V. Safronov","orcid":"0000-0002-4614-3184","position":5,"is_corresponding":false},{"id":1092227,"name":"Pavel Belan","orcid":"0000-0001-5429-3716","position":6,"is_corresponding":false},{"id":927689,"name":"Nana Voitenko","orcid":"0000-0002-2450-3134","position":7,"is_corresponding":false},{"id":927681,"name":"Volodymyr Krotov","orcid":"0000-0001-5737-3252","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T01:14:46.760245Z","pmid":"36713779","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}