IL-4 deficiency is associated with mechanical hypersensitivity in mice.

Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We inve...

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Autores principales:	Nurcan Üçeyler, Tengü Topuzoğlu, Peter Schiesser, Saskia Hahnenkamp, Claudia Sommer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4f4324a638b94d52862abbe721984975
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spelling	oai:doaj.org-article:4f4324a638b94d52862abbe7219849752021-11-18T07:33:10ZIL-4 deficiency is associated with mechanical hypersensitivity in mice.1932-620310.1371/journal.pone.0028205https://doaj.org/article/4f4324a638b94d52862abbe7219849752011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22164245/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.Nurcan ÜçeylerTengü TopuzoğluPeter SchiesserSaskia HahnenkampClaudia SommerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28205 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nurcan Üçeyler Tengü Topuzoğlu Peter Schiesser Saskia Hahnenkamp Claudia Sommer IL-4 deficiency is associated with mechanical hypersensitivity in mice.
description	Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.
format	article
author	Nurcan Üçeyler Tengü Topuzoğlu Peter Schiesser Saskia Hahnenkamp Claudia Sommer
author_facet	Nurcan Üçeyler Tengü Topuzoğlu Peter Schiesser Saskia Hahnenkamp Claudia Sommer
author_sort	Nurcan Üçeyler
title	IL-4 deficiency is associated with mechanical hypersensitivity in mice.
title_short	IL-4 deficiency is associated with mechanical hypersensitivity in mice.
title_full	IL-4 deficiency is associated with mechanical hypersensitivity in mice.
title_fullStr	IL-4 deficiency is associated with mechanical hypersensitivity in mice.
title_full_unstemmed	IL-4 deficiency is associated with mechanical hypersensitivity in mice.
title_sort	il-4 deficiency is associated with mechanical hypersensitivity in mice.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/4f4324a638b94d52862abbe721984975
work_keys_str_mv	AT nurcanuceyler il4deficiencyisassociatedwithmechanicalhypersensitivityinmice AT tengutopuzoglu il4deficiencyisassociatedwithmechanicalhypersensitivityinmice AT peterschiesser il4deficiencyisassociatedwithmechanicalhypersensitivityinmice AT saskiahahnenkamp il4deficiencyisassociatedwithmechanicalhypersensitivityinmice AT claudiasommer il4deficiencyisassociatedwithmechanicalhypersensitivityinmice
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IL-4 deficiency is associated with mechanical hypersensitivity in mice.

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