Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain

The sigma-1 receptor (Sig-1R) plays an important role in spinal pain transmission by increasing phosphorylation of the N-methyl-D-aspartate (NMDA) receptor GluN1 subunit (pGluN1). As a result Sig-1R has been suggested as a novel therapeutic target for prevention of chronic pain. Here we investigated...

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Autores principales:	Sheu-Ran Choi, Ho Jae Han, Alvin J. Beitz, Jang-Hern Lee
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Interleukin-1β Sigma-1 receptor Astrocytes Phosphorylation Neuropathic pain Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/9b3f0c119ad542068f5809bc8ee7c38b
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spelling	oai:doaj.org-article:9b3f0c119ad542068f5809bc8ee7c38b2021-11-14T04:29:06ZIntrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain0753-332210.1016/j.biopha.2021.112272https://doaj.org/article/9b3f0c119ad542068f5809bc8ee7c38b2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010568https://doaj.org/toc/0753-3322The sigma-1 receptor (Sig-1R) plays an important role in spinal pain transmission by increasing phosphorylation of the N-methyl-D-aspartate (NMDA) receptor GluN1 subunit (pGluN1). As a result Sig-1R has been suggested as a novel therapeutic target for prevention of chronic pain. Here we investigated whether interleukin-1β (IL-1β) modulates the expression of the Sig-1R in spinal astrocytes during the early phase of nerve injury, and whether this modulation affects spinal pGluN1 expression and the development of neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve. Repeated intrathecal (i.t.) administration of IL-1β from days 0–3 post-surgery significantly reduced the increased pGluN1 expression at the Ser896 and Ser897 sites in the ipsilateral spinal cord, as well as, the development of mechanical allodynia and thermal hyperalgesia in the ipsilateral hind paw of CCI mice, which were restored by co-administration of IL-1 receptor antagonist with IL-1β. Sciatic nerve injury increased the expression of Sig-1R in astrocytes of the ipsilateral spinal cord, and this increase was suppressed by i.t. administration of IL-1β. Agonistic stimulation of the Sig-1R with PRE084 restored pGluN1 expression and the development of mechanical allodynia that were originally suppressed by IL-1β in CCI mice. Collectively these results demonstrate that IL-1β administration during the induction phase of neuropathic pain produces an analgesic effect on neuropathic pain development by controlling the expression of Sig-1R in spinal astrocytes.Sheu-Ran ChoiHo Jae HanAlvin J. BeitzJang-Hern LeeElsevierarticleInterleukin-1βSigma-1 receptorAstrocytesPhosphorylationNeuropathic painTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112272- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Interleukin-1β Sigma-1 receptor Astrocytes Phosphorylation Neuropathic pain Therapeutics. Pharmacology RM1-950
spellingShingle	Interleukin-1β Sigma-1 receptor Astrocytes Phosphorylation Neuropathic pain Therapeutics. Pharmacology RM1-950 Sheu-Ran Choi Ho Jae Han Alvin J. Beitz Jang-Hern Lee Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
description	The sigma-1 receptor (Sig-1R) plays an important role in spinal pain transmission by increasing phosphorylation of the N-methyl-D-aspartate (NMDA) receptor GluN1 subunit (pGluN1). As a result Sig-1R has been suggested as a novel therapeutic target for prevention of chronic pain. Here we investigated whether interleukin-1β (IL-1β) modulates the expression of the Sig-1R in spinal astrocytes during the early phase of nerve injury, and whether this modulation affects spinal pGluN1 expression and the development of neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve. Repeated intrathecal (i.t.) administration of IL-1β from days 0–3 post-surgery significantly reduced the increased pGluN1 expression at the Ser896 and Ser897 sites in the ipsilateral spinal cord, as well as, the development of mechanical allodynia and thermal hyperalgesia in the ipsilateral hind paw of CCI mice, which were restored by co-administration of IL-1 receptor antagonist with IL-1β. Sciatic nerve injury increased the expression of Sig-1R in astrocytes of the ipsilateral spinal cord, and this increase was suppressed by i.t. administration of IL-1β. Agonistic stimulation of the Sig-1R with PRE084 restored pGluN1 expression and the development of mechanical allodynia that were originally suppressed by IL-1β in CCI mice. Collectively these results demonstrate that IL-1β administration during the induction phase of neuropathic pain produces an analgesic effect on neuropathic pain development by controlling the expression of Sig-1R in spinal astrocytes.
format	article
author	Sheu-Ran Choi Ho Jae Han Alvin J. Beitz Jang-Hern Lee
author_facet	Sheu-Ran Choi Ho Jae Han Alvin J. Beitz Jang-Hern Lee
author_sort	Sheu-Ran Choi
title	Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
title_short	Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
title_full	Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
title_fullStr	Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
title_full_unstemmed	Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
title_sort	intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/9b3f0c119ad542068f5809bc8ee7c38b
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Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain

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