Abstract

BACKGROUND: Transient receptor potential vanilloid subtype 1 (TRPV1) is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1) activation. Reactive oxygen species (ROS) production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG) neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-alpha-phenylnitrone (PBN), were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies.

RESULTS: The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin.

CONCLUSION: TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons.

Document Type

Article

Publication Date

6-17-2009

Notes/Citation Information

Published in Molecular Pain, v. 5, 31.

© 2009 Ma et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1186/1744-8069-5-31

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