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First published on December 18, 2007; DOI: 10.1124/mol.107.041707

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Received for publication September 10, 2007.
Revised December 14, 2007.
Accepted for publication December 14, 2007.

Direct Role of Streptozotocin in Inducing Thermal Hyperalgesia by Enhanced Expression of TRPV1 in Sensory Neurons

Reddy M Pabbidi 1, De-Shou Cao 1, Arti Parihar 1, Mary E Pauza 2, Louis S. Premkumar 1*

1 Southern Illinois University School of Medicine 2 SIU School of Medicine

* Address correspondence to: E-mail: lpremkumar{at}siumed.edu

Abstract

Streptozotocin (STZ) is a diabetogenic agent extensively used to induce diabetes and to study complications including diabetic peripheral neuropathy (DPN). While studying the influence of TRPV1 on DPN in the STZ-induced diabetic mouse model, we found that a proportion of STZ-treated mice was non-diabetic, but still exhibited hyperalgesia. In order to understand the mechanism underlying this phenomenon, dorsal root ganglion (DRG) neurons and stably TRPV1 expressing HEK293T cells were used to study the expression and the function of TRPV1. Incubation of DRG neurons with STZ resulted in a significant increase in the amplitude of capsaicin-induced TRPV1-mediated current and Ca2+ influx as compared to vehicle-treated sister cultures. It was also found that STZ treatment induced higher levels of reactive oxygen species (ROS), which was abolished with concomitant treatment with catalase. Treatment of cells with H2O2 mimicked the effects of STZ. Western blot analysis revealed an increase in TRPV1 protein content and phospho p38 (p-p38) MAPK levels in DRG of STZ-injected diabetic and non-diabetic hyperalgesic mice as compared to control mice. Furthermore, in stably TRPV1 expressing HEK293T cells, STZ treatment induced an increase in TRPV1 protein content and p-p38 MAPK levels, which was abolished with concomitant treatment with catalase or p38 MAPK inhibitor. These results reveal that STZ has a direct action on neurons and modulates expression and function of TRPV1, a nociceptive ion channel that is responsible for inflammatory thermal pain.


Key words: Capsaicin/vanilloid, Func. analysis receptor/ion channel mutants


This article has been cited by other articles:


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T. J. Tamsett, K. E. Picchione, and A. Bhattacharjee
NAD+ Activates KNa Channels in Dorsal Root Ganglion Neurons
J. Neurosci., April 22, 2009; 29(16): 5127 - 5134.
[Abstract] [Full Text] [PDF]


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