| Title |
Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats
|
|---|---|
| Published in |
The Journal of Headache and Pain, August 2016
|
| DOI | 10.1186/s10194-016-0665-2 |
| Pubmed ID | |
| 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 |
| Abstract |
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. 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. 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. The present results demonstrate that suppressing p38 and ERK activity affects TGF-β1-induced analgesia during neuropathy. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 3% |
| Unknown | 39 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 15% |
| Student > Master | 5 | 13% |
| Student > Ph. D. Student | 4 | 10% |
| Student > Doctoral Student | 3 | 8% |
| Student > Bachelor | 3 | 8% |
| Other | 8 | 20% |
| Unknown | 11 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 25% |
| Neuroscience | 4 | 10% |
| Nursing and Health Professions | 3 | 8% |
| Environmental Science | 3 | 8% |
| Biochemistry, Genetics and Molecular Biology | 2 | 5% |
| Other | 5 | 13% |
| Unknown | 13 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 August 2016.
All research outputs
#18,572,005
of 23,849,058 outputs
Outputs from The Journal of Headache and Pain
#1,172
of 1,417 outputs
Outputs of similar age
#252,704
of 346,789 outputs
Outputs of similar age from The Journal of Headache and Pain
#17
of 24 outputs
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