The Input-Output Relation of Primary Nociceptive Neurons is Determined by the Morphology of the Peripheral Nociceptive Terminals.
Action Potentials
/ physiology
Capsaicin
/ pharmacology
Computer Simulation
Humans
Models, Neurological
Neuralgia
/ physiopathology
Nociception
Nociceptors
/ physiology
Peripheral Nerves
/ physiology
Peripheral Nervous System Diseases
/ physiopathology
Presynaptic Terminals
/ physiology
Sensory Receptor Cells
/ physiology
Sodium Channels
/ drug effects
Synaptic Transmission
/ drug effects
axon
inflammatory pain
neuropathic pain
nociception
nociceptive terminal
sodium channels
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
02 12 2020
02 12 2020
Historique:
received:
18
06
2020
revised:
19
10
2020
accepted:
21
10
2020
pubmed:
30
10
2020
medline:
13
2
2021
entrez:
29
10
2020
Statut:
ppublish
Résumé
The output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree. The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential (AP) firing. However, in the majority of cases, noxious stimuli activate multiple terminals; thus, the output of the nociceptive neuron is defined by the integration and computation of the inputs of the individual terminals. Here, we used a computational model of nociceptive terminal tree to study how the architecture of the terminal tree affects the input-output relation of the primary nociceptive neurons. We show that the input-output properties of the nociceptive neurons depend on the length, the axial resistance (Ra), and location of individual terminals. Moreover, we show that activation of multiple terminals by a capsaicin-like current allows summation of the responses from individual terminals, thus leading to increased nociceptive output. Stimulation of the terminals in simulated models of inflammatory or neuropathic hyperexcitability led to a change in the temporal pattern of AP firing, emphasizing the role of temporal code in conveying key information about changes in nociceptive output in pathologic conditions, leading to pain hypersensitivity.
Identifiants
pubmed: 33115929
pii: JNEUROSCI.1546-20.2020
doi: 10.1523/JNEUROSCI.1546-20.2020
pmc: PMC7724132
doi:
Substances chimiques
Sodium Channels
0
Capsaicin
S07O44R1ZM
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9346-9363Informations de copyright
Copyright © 2020 the authors.
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