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




Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats - Download this document for free, or read online. Document in PDF available to download.

The Journal of Headache and Pain

, 17:72

First Online: 19 August 2016Received: 18 April 2016Accepted: 09 August 2016

Abstract

BackgroundTransforming 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.

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

ResultsThe 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.

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

KeywordsTransforming growth factor-β p38 Extracellular signal-regulated kinase Chronic constriction injury Neuropathic pain  Download fulltext PDF



Author: Nan-Fu Chen - Wu-Fu Chen - Chun-Sung Sung - Ching-Hsiang Lu - Chun-Lin Chen - Han-Chun Hung - Chien-Wei Feng - Chun-Hong C

Source: https://link.springer.com/



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