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

40Citations
Citations of this article
41Readers
Mendeley users who have this article in their library.

This article is free to access.

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.

Cite

CITATION STYLE

APA

Chen, N. F., Chen, W. F., Sung, C. S., Lu, C. H., Chen, C. L., Hung, H. C., … Huang, S. Y. (2016). Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats. Journal of Headache and Pain, 17(1). https://doi.org/10.1186/s10194-016-0665-2

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free