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Capsaicin-Induced Activation of ERK1/2 and Its Involvement in GAP-43 Expression and CGRP Depletion in Organotypically Cultured DRG Neurons

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Abstract

Low concentrations of capsaicin (CAP) stimulate and high concentrations of CAP can be toxic to the primary sensory neurons of the dorsal root ganglion (DRG). CAP induces the phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in DRG neurons. The effect of the activation of ERK1/2 by different concentrations of CAP on growth-associated protein 43 (GAP-43) expression and calcitonin gene-related peptide (CGRP) depletion in DRG neurons remains unknown. In the present study, organotypic embryonic 15-day-old rat DRG explants were used to determine the effect of different concentrations of CAP on GAP-43 expression and CGRP depletion. The results showed that, compared to unstimulated control cultures, GAP-43 and pERK1/2 protein levels increased at a low concentration (2 μmol/L) of CAP and decreased at a higher concentration (10 μmol/L). The number of CGRP-immunoreactive (IR) migrating neurons also decreased in CAP-treated cultures. The increase in GAP-43 levels and CGRP depletion could be blocked by the administration of ERK1/2 inhibitor PD98059. The results of the present study imply that CAP at different concentrations has different effects on GAP-43 expression and CGRP depletion. These effects were involved in the activation of ERK1/2 in organotypically cultured DRG neurons stimulated with CAP. These data may provide new insights for further development potential therapeutic applications of CAP with moderate dose on neurogenic inflammation.

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Abbreviations

CAP:

Capsaicin

CNS:

Central nervous system

CGRP:

Calcitonin gene-related peptide

DMEM/F-12:

Dulbecco’s Modified Eagle Medium with F-12 supplement

DMSO:

Dimethyl sulfoxide

DRG:

Dorsal root ganglion

DRGs:

Dorsal root ganglia

E15:

Embryonic day 15

ERK:

Extracellular signal-regulated protein kinase

ERK1/2:

Extracellular signal-regulated protein kinases 1/2

GAP-43:

Growth-associated protein-43

IR:

Immunoreactive

MAP2:

Microtubule-associated protein 2

pERK1/2:

Phosphorylated-ERK1/2

PBS:

Phosphate buffer saline

TRPV1:

Transient receptor potential vanilloid 1

VR1:

Vanilloid receptor-1

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81000517), the Foundation for the Doctoral Program New Teacher of State Education Ministry of China (No. 20090131120013), and China Postdoctoral Science Foundation (No. 200904501203).

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Authors and Affiliations

  1. Faculty of Clinical Medicine, Shandong University School of Medicine, Jinan, 250012, China

    Yunfeng Li, Youzheng Xu & Hong Zhang

  2. Department of Histology and Embryology, Binzhou Medical College, Binzhou, 256603, China

    Guixiang Liu

  3. Department of Orthopaedics, Shandong University Qilu Hospital, Jinan, 250012, China

    Hao Li

  4. Department of Anatomy, Shandong University School of Medicine, 44 West Wenhua Xi Road, Jinan, 250012, Shandong Province, China

    Zhen Liu

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  1. Yunfeng Li
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  2. Guixiang Liu
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  5. Hong Zhang
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Correspondence to Zhen Liu.

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Li, Y., Liu, G., Li, H. et al. Capsaicin-Induced Activation of ERK1/2 and Its Involvement in GAP-43 Expression and CGRP Depletion in Organotypically Cultured DRG Neurons. Cell Mol Neurobiol 33, 433–441 (2013). https://doi.org/10.1007/s10571-013-9909-8

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