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Open Access 01-12-2016 | Research article

Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats

Authors: Nan-Fu Chen, Wu-Fu Chen, Chun-Sung Sung, Ching-Hsiang Lu, Chun-Lin Chen, Han-Chun Hung, Chien-Wei Feng, Chun-Hong Chen, Kuan-Hao Tsui, Hsiao-Mei Kuo, Hui-Min David Wang, Zhi-Hong Wen, Shi-Ying Huang

Published in: The Journal of Headache and Pain | Issue 1/2015

Abstract

Background

Transforming growth factor-βs (TGF-βs) are a group of multifunctional proteins that have neuroprotective roles in various experimental models. We previously reported that intrathecal (i.t.) injections of TGF-β1 significantly inhibit neuropathy-induced thermal hyperalgesia, spinal microglia and astrocyte activation, as well as upregulation of tumor necrosis factor-α. However, additional cellular mechanisms for the antinociceptive effects of TGF-β1, such as the mitogen-activated protein kinase (MAPK) pathway, have not been elucidated. During persistent pain, activation of MAPKs, especially p38 and extracellular signal-regulated kinase (ERK), have crucial roles in the induction and maintenance of pain hypersensitivity, via both nontranscriptional and transcriptional regulation. In the present study, we used a chronic constriction injury (CCI) rat model to explore the role of spinal p38 and ERK in the analgesic effects of TGF-β1.

Methods

We investigated the cellular mechanisms of the antinociceptive effects of i.t. injections of TGF-β1 in CCI induced neuropathic rats by spinal immunohistofluorescence analyses.

Results

The results demonstrated that the antinociceptive effects of TGF-β1 (5 ng) were maintained at greater than 50 % of the maximum possible effect in rats with CCI for at least 6 h after a single i.t. administration. Thus, we further examined these alterations in spinal p38 and ERK from 0.5 to 6 h after i.t. administration of TGF-β1. TGF-β1 significantly attenuated CCI-induced upregulation of phosphorylated p38 (phospho-p38) and phosphorylated ERK (phospho-ERK) expression in the dorsal horn of the lumbar spinal cord. Double immunofluorescence staining illustrated that upregulation of spinal phospho-p38 was localized to neurons, activated microglial cells, and activated astrocytes in rats with CCI. Additionally, increased phospho-ERK occurred in activated microglial cells and activated astrocytes. Furthermore, i.t. administration of TGF-β1 markedly inhibited phospho-p38 upregulation in neurons, microglial cells, and astrocytes. However, i.t. injection of TGF-β1 also reduced phospho-ERK upregulation in microglial cells and astrocytes.

Conclusions

The present results demonstrate that suppressing p38 and ERK activity affects TGF-β1-induced analgesia during neuropathy.

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Title: Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats
Authors: Nan-Fu Chen
Wu-Fu Chen
Chun-Sung Sung
Ching-Hsiang Lu
Chun-Lin Chen
Han-Chun Hung
Chien-Wei Feng
Chun-Hong Chen
Kuan-Hao Tsui
Hsiao-Mei Kuo
Hui-Min David Wang
Zhi-Hong Wen
Shi-Ying Huang
Publication date: 01-12-2016
Publisher: Springer Milan
Published in: The Journal of Headache and Pain / Issue 1/2015
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-016-0665-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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