Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model

Opioids are widely used for pain relief; however, chronic opioid use causes a paradoxical state of enhanced pain sensitivity, termed “Opioid-induced hyperalgesia (OIH).” Despite the clinical importance of OIH, the detailed mechanism by which it enhances pain sensitivity remains unclear. In this stud...

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Autores principales:	Austin Kearns, Jazmine Jayasi, Xin Liu, Jigong Wang, Yuqiang Shi, Jin Mo Chung, Jun-Ho La, Shao-Jun Tang, Chilman Bae
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	opioid-induced hyperalgesia spinal cord dorsal horn neurokinin 1 receptor GABAergic interneurons central sensitization morphine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/a985fcbed4b740049b7845885ae721ae
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spelling	oai:doaj.org-article:a985fcbed4b740049b7845885ae721ae2021-11-18T09:21:22ZNeuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model1663-356310.3389/fnsyn.2021.748929https://doaj.org/article/a985fcbed4b740049b7845885ae721ae2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnsyn.2021.748929/fullhttps://doaj.org/toc/1663-3563Opioids are widely used for pain relief; however, chronic opioid use causes a paradoxical state of enhanced pain sensitivity, termed “Opioid-induced hyperalgesia (OIH).” Despite the clinical importance of OIH, the detailed mechanism by which it enhances pain sensitivity remains unclear. In this study, we tested whether repeated morphine induces a neuronal circuit polarization in the mouse spinal dorsal horn (SDH). Transgenic mice expressing GFP to neurokinin 1 receptor-expressing neurons (sNK1Rn) and GABAergic interneurons (sGABAn) that received morphine [20 mg/kg, once daily for four consecutive days (i.p.)] developed mechanical hypersensitivity. Repeated morphine altered synaptic strengths in the SDH as a specific cell-type but not in a gender-dependent manner. In sNK1Rn and non-tonic firing neurons, repeated morphine treatment significantly increased frequency of spontaneous excitatory postsynaptic current (sEPSC) and evoked EPSC (eEPSC). In addition, repeated morphine treatment significantly decreased evoked inhibitory postsynaptic current (eIPSC) in sNK1Rn. Conversely, in sGABAn and tonic firing neurons, repeated morphine treatment significantly decreased sEPSC frequency and eEPSC, but had no change of eIPSC in sGABAn. Interestingly, repeated morphine treatment significantly decreased neuronal rheobase of sNK1Rn but had no effect on sGABAn. These findings suggest that spinal neuronal circuit polarization maybe the mechanism of OIH and identify a potential therapeutic mechanism to prevent or treat opioid-induced pain.Austin KearnsJazmine JayasiXin LiuJigong WangYuqiang ShiJin Mo ChungJun-Ho LaShao-Jun TangChilman BaeChilman BaeFrontiers Media S.A.articleopioid-induced hyperalgesiaspinal cord dorsal hornneurokinin 1 receptorGABAergic interneuronscentral sensitizationmorphineNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Synaptic Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	opioid-induced hyperalgesia spinal cord dorsal horn neurokinin 1 receptor GABAergic interneurons central sensitization morphine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	opioid-induced hyperalgesia spinal cord dorsal horn neurokinin 1 receptor GABAergic interneurons central sensitization morphine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Austin Kearns Jazmine Jayasi Xin Liu Jigong Wang Yuqiang Shi Jin Mo Chung Jun-Ho La Shao-Jun Tang Chilman Bae Chilman Bae Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model
description	Opioids are widely used for pain relief; however, chronic opioid use causes a paradoxical state of enhanced pain sensitivity, termed “Opioid-induced hyperalgesia (OIH).” Despite the clinical importance of OIH, the detailed mechanism by which it enhances pain sensitivity remains unclear. In this study, we tested whether repeated morphine induces a neuronal circuit polarization in the mouse spinal dorsal horn (SDH). Transgenic mice expressing GFP to neurokinin 1 receptor-expressing neurons (sNK1Rn) and GABAergic interneurons (sGABAn) that received morphine [20 mg/kg, once daily for four consecutive days (i.p.)] developed mechanical hypersensitivity. Repeated morphine altered synaptic strengths in the SDH as a specific cell-type but not in a gender-dependent manner. In sNK1Rn and non-tonic firing neurons, repeated morphine treatment significantly increased frequency of spontaneous excitatory postsynaptic current (sEPSC) and evoked EPSC (eEPSC). In addition, repeated morphine treatment significantly decreased evoked inhibitory postsynaptic current (eIPSC) in sNK1Rn. Conversely, in sGABAn and tonic firing neurons, repeated morphine treatment significantly decreased sEPSC frequency and eEPSC, but had no change of eIPSC in sGABAn. Interestingly, repeated morphine treatment significantly decreased neuronal rheobase of sNK1Rn but had no effect on sGABAn. These findings suggest that spinal neuronal circuit polarization maybe the mechanism of OIH and identify a potential therapeutic mechanism to prevent or treat opioid-induced pain.
format	article
author	Austin Kearns Jazmine Jayasi Xin Liu Jigong Wang Yuqiang Shi Jin Mo Chung Jun-Ho La Shao-Jun Tang Chilman Bae Chilman Bae
author_facet	Austin Kearns Jazmine Jayasi Xin Liu Jigong Wang Yuqiang Shi Jin Mo Chung Jun-Ho La Shao-Jun Tang Chilman Bae Chilman Bae
author_sort	Austin Kearns
title	Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model
title_short	Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model
title_full	Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model
title_fullStr	Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model
title_full_unstemmed	Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model
title_sort	neuron type-dependent synaptic activity in the spinal dorsal horn of opioid-induced hyperalgesia mouse model
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a985fcbed4b740049b7845885ae721ae
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Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model

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