Structural plasticity of axon initial segment in spinal cord neurons underlies inflammatory pain.

Autor:	Caspi Y; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel., Mazar M; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel., Kushnir Y; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel., Mazor Y; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.; Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel., Katz B; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel., Lev S; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel., Binshtok AM; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2023 Jun 01; Vol. 164 (6), pp. 1388-1401. Date of Electronic Publication: 2022 Nov 29.
DOI:	10.1097/j.pain.0000000000002829
Abstrakt:	Abstract: Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site-the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity. We show that in naive conditions, AIS in SDH inhibitory neurons is located closer to the soma than in excitatory neurons. Shortly after inducing inflammation, when the inflammatory hyperalgesia is at its peak, AIS in inhibitory neurons is shifted distally away from the soma. The shift in AIS location is accompanied by the decrease in excitability of SDH inhibitory neurons. These AIS location and excitability changes are selective for inhibitory neurons and reversible. We show that AIS shift back close to the soma, and SDH inhibitory neurons' excitability increases to baseline levels following recovery from inflammatory hyperalgesia. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of inflammatory pain-mediated AIS plasticity in the central nervous system, which differentially affects the excitability of inhibitory SDH neurons and contributes to inflammatory hyperalgesia. (Copyright © 2023 International Association for the Study of Pain.)
Databáze:	MEDLINE
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