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Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice

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Abstract

Transgenic mice with a small hairpin RNA construct interfering with the expression of transient receptor potential vanilloid 1 (TRPV1) were created by lentiviral transgenesis. TRPV1 expression level in transgenic mice was reduced to 8% while the expression of ankyrin repeat domain 1 (TRPA1) was unchanged. Ear oedema induced by topical application of TRPV1 agonist capsaicin was completely absent in TRPV1 knockdown mice. Thermoregulatory behaviour in relation to environmental thermopreference (30 vs. 35°C) was slightly impaired in male knockdown mice, but the reduction of TRPV1 function was not associated with enhanced hyperthermia. TRPV1 agonist resiniferatoxin induced hypothermia and tail vasodilatation was markedly inhibited in knockdown mice. In conclusion, shRNA-mediated knock down of the TRPV1 receptor in mice induced robust inhibition of the responses to TRPV1 agonists without altering the expression, gating function or neurogenic oedema provoked by TRPA1 activation. Thermoregulatory behaviour in response to heat was inhibited, but enhanced hyperthermia was not observed.

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Abbreviations

TRPV1:

Transient receptor potential vanilloid 1

TRPA1:

Transient receptor potential ankyrin repeat domain 1

shRNA:

Small hairpin RNA

siRNA:

Small interfering RNA

RTX:

Resiniferatoxin

GFP:

Green fluorescence protein

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Acknowledgments

This work was supported by a Hungarian Grant (OTKA NK-78059). The authors thank István Likó, Mrs. Anna Búzási and Mrs. Dóra Ömböli for their expert technical assistance in the experiments.

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Correspondence to Zoltán Sándor.

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Tóth, D.M., Szőke, É., Bölcskei, K. et al. Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice. Cell. Mol. Life Sci. 68, 2589–2601 (2011). https://doi.org/10.1007/s00018-010-0569-2

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