Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice.
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.
Analgesics Research Laboratory, University of Pécs and Gedeon Richter PLC, Szigeti út 12, Pécs, 7624, Hungary.
Dániel Márton
DM
Tóth
Eva
E
Szoke
Kata
K
Bölcskei
Krisztián
K
Kvell
Balázs
B
Bender
Zsuzsanna
Z
Bosze
János
J
Szolcsányi
Zoltán
Z
Sándor
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000235:genetics*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020078:Neurogenic Inflammation / Q000235:genetics*; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology
D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse