Antinociceptive effect of antisense oligonucleotides against the vanilloid receptor VR1/TRPV1
Section snippets
Introductory statement
The capsaicin or vanilloid receptor VR1 is a member of the transient receptor potential (TRP) family and is thus also referred to as TRPV1 (Montell et al., 2002). It is predominantly expressed by nociceptive sensory neurons and functions as a cation channel (Caterina et al., 1997, Tominaga et al., 1998). TRPV1 is activated by a wide array of pain-producing stimuli including capsaicin, noxious heat and low pH (for reviews, see Cortright and Szallasi, 2004, Tominaga and Tominaga, 2005) and is
Oligonucleotides
Unmodified DNA oligonucleotides as well as phosphorothioates for in vitro and cell culture experiments were obtained from MWG Biotech AG (Ebersberg, Germany). Oligonucleotides for in vivo applications were purchased from IBA GmbH (Goettingen, Germany).
The sequences of oligonucleotides V15 and V15MM were:
V15: CAT GTC ATG ACG GTT AGG
V15MM: CAT GCT ATG AGC GTT GAG.
Cell culture and transfection
Cos-7 cells (African green monkey kidney fibroblasts) were grown in a humidified atmosphere at 37 °C with 5% CO2 in Dulbecco's modified
Results
To investigate the functional role of the vanilloid receptor TRPV1 in neuropathic pain processes in more detail, the analgesic effects of a low molecular weight receptor antagonist and an AS ODN directed against the TRPV1 mRNA were investigated and compared in vitro and in vivo. The plasticity of TRPV1 expression after the neuropathic lesion and under TRPV1 antisense treatment was monitored by immunocytochemistry.
Discussion
The aim of the present study was to investigate the involvement of TRPV1 in neuropathic pain of rats subjected to SNL. Two complementary approaches have been employed to this end: we used a low molecular weight compound that acts as a receptor antagonist as well as AS ODNs against the TRPV1 mRNA. The AS ODN has previously been shown to induce RNase H mediated cleavage of TRPV1 mRNA in vitro (Kurreck et al., 2002a) and to silence TRPV1-GFP expression in cell culture (Grünweller et al., 2003).
Acknowledgments
We thank Sabine Hees, Petra Lattermann, Elke Rodenberg-Frank, Petra Sack, Heidemarie Schneider, Elke Schumacher, Marion Zibuschka, Thomas Vanderbrück and Birgit Bieber for excellent technical assistance. This study was supported by the German Ministry for Research and Technology (Grant 01GG9818/0) and the RiNA network for RNA technologies (financed by the City of Berlin, the Federal Ministry of Education and Research and the European Regional Development Fund).
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