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Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons

Chronic pain is one of the most devastating and unpleasant conditions, associated with many pathological states. Tissue or nerve injuries induce extensive neurobiological plasticity in nociceptive neurons, which leads to chronic pain. Recent studies suggest that cyclin-dependent kinase 5 (CDK5) in p...

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Autores principales: Tiwari, Manindra Nath, Hall, Bradford E, Ton, Anh-Tuan, Ghetti, Re, Terse, Anita, Amin, Niranjana, Chung, Man-Kyo, Kulkarni, Ashok B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687939/
https://www.ncbi.nlm.nih.gov/pubmed/37982142
http://dx.doi.org/10.1177/17448069231218353
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author Tiwari, Manindra Nath
Hall, Bradford E
Ton, Anh-Tuan
Ghetti, Re
Terse, Anita
Amin, Niranjana
Chung, Man-Kyo
Kulkarni, Ashok B
author_facet Tiwari, Manindra Nath
Hall, Bradford E
Ton, Anh-Tuan
Ghetti, Re
Terse, Anita
Amin, Niranjana
Chung, Man-Kyo
Kulkarni, Ashok B
author_sort Tiwari, Manindra Nath
collection PubMed
description Chronic pain is one of the most devastating and unpleasant conditions, associated with many pathological states. Tissue or nerve injuries induce extensive neurobiological plasticity in nociceptive neurons, which leads to chronic pain. Recent studies suggest that cyclin-dependent kinase 5 (CDK5) in primary afferents is a key neuronal kinase that modulates nociception through phosphorylation under pathological conditions. However, the impact of the CDK5 on nociceptor activity especially in human sensory neurons is not known. To determine the CDK5-mediated regulation of human dorsal root ganglia (hDRG) neuronal properties, we have performed the whole-cell patch clamp recordings in neurons dissociated from hDRG. CDK5 activation induced by overexpression of p35 depolarized the resting membrane potential (RMP) and reduced the rheobase currents as compared to the control neurons. CDK5 activation changed the shape of the action potential (AP) by increasing AP -rise time, -fall time, and -half width. The application of a prostaglandin E2 (PG) and bradykinin (BK) cocktail in control hDRG neurons induced the depolarization of RMP and the reduction of rheobase currents along with increased AP rise time. However, PG and BK applications failed to induce any significant changes in the p35-overexpressing group. We conclude that, in dissociated hDRGs neurons, CDK5 activation through the overexpression of p35 broadens the AP and that CDK5 may play important roles in the modulation of AP properties in human primary afferents under the condition in which CDK5 is upregulated, contributing to chronic pain.
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spelling pubmed-106879392023-11-30 Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons Tiwari, Manindra Nath Hall, Bradford E Ton, Anh-Tuan Ghetti, Re Terse, Anita Amin, Niranjana Chung, Man-Kyo Kulkarni, Ashok B Mol Pain Research Article Chronic pain is one of the most devastating and unpleasant conditions, associated with many pathological states. Tissue or nerve injuries induce extensive neurobiological plasticity in nociceptive neurons, which leads to chronic pain. Recent studies suggest that cyclin-dependent kinase 5 (CDK5) in primary afferents is a key neuronal kinase that modulates nociception through phosphorylation under pathological conditions. However, the impact of the CDK5 on nociceptor activity especially in human sensory neurons is not known. To determine the CDK5-mediated regulation of human dorsal root ganglia (hDRG) neuronal properties, we have performed the whole-cell patch clamp recordings in neurons dissociated from hDRG. CDK5 activation induced by overexpression of p35 depolarized the resting membrane potential (RMP) and reduced the rheobase currents as compared to the control neurons. CDK5 activation changed the shape of the action potential (AP) by increasing AP -rise time, -fall time, and -half width. The application of a prostaglandin E2 (PG) and bradykinin (BK) cocktail in control hDRG neurons induced the depolarization of RMP and the reduction of rheobase currents along with increased AP rise time. However, PG and BK applications failed to induce any significant changes in the p35-overexpressing group. We conclude that, in dissociated hDRGs neurons, CDK5 activation through the overexpression of p35 broadens the AP and that CDK5 may play important roles in the modulation of AP properties in human primary afferents under the condition in which CDK5 is upregulated, contributing to chronic pain. SAGE Publications 2023-11-29 /pmc/articles/PMC10687939/ /pubmed/37982142 http://dx.doi.org/10.1177/17448069231218353 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Tiwari, Manindra Nath
Hall, Bradford E
Ton, Anh-Tuan
Ghetti, Re
Terse, Anita
Amin, Niranjana
Chung, Man-Kyo
Kulkarni, Ashok B
Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons
title Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons
title_full Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons
title_fullStr Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons
title_full_unstemmed Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons
title_short Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons
title_sort activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687939/
https://www.ncbi.nlm.nih.gov/pubmed/37982142
http://dx.doi.org/10.1177/17448069231218353
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