Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well.
OBJECTIVE
Resiniferatoxin, the most potent agonist of inflammatory pain/vanilloid receptor/cation channel (TRPV1) can be used for neuron subtype specific ablation of pain generating cells at the level of the peripheral nervous system by Ca(2+)-excytotoxicity. Molecular neurosurgery is an emerging technology either to alleviate severe pain in cancer or treat/prevent different local neuropathies. Our aim was determining sensory modalities that may be lost after resiniferatoxin treatment.


METHODS
Newborn or adult mice were treated with resiniferatoxin, then changes in chemical and heat sensitivity were correlated with alterations of the cell composition of sensory ganglions.


RESULTS
Only mice treated at adult age became less sensitive to heat stimuli, while both treatment groups lost sensitivity to specific vanilloid agonists of TRPV1 and, interestingly, to allyl-isothiocyanate, a selective agonist of TRPA1. Our in vivo and post mortem analytical results confirmed that TRPV1 and TRPA1 function together and resiniferatoxin-mediated neurosurgery removes both sensor molecules.


CONCLUSIONS
In adult mice resiniferatoxin causes: i) desensitization to heat and ii) sensitization to cold. Cold hyperalgesia, an imbalance in thermosensation, might be conferred by a prominent cold receptor that is expressed in surviving resiniferatoxin-resistant sensory neurons and compensates for pain signals lost with TRPA1 and TRPV1 double positive cells in the peripheral nervous system.
Pecze
László
L
Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
Pelsoczi
Péter
P
Kecskés
Miklós
M
Winter
Zoltán
Z
Papp
András
A
Kaszás
Krisztián
K
Letoha
Tamás
T
Vizler
Csaba
C
Oláh
Zoltán
Z
D000818:Animals; D015153:Blotting, Western; D003080:Cold Temperature; D004224:Diterpenes / Q000494:pharmacology*; D006358:Hot Temperature; D007150:Immunohistochemistry; D051379:Mice; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism
D004224:Diterpenes; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C024353:resiniferatoxin