Ablation of TrpV1 neurons reveals their selective role in thermal pain sensation.
Here we make use of neural ablation to investigate the properties of the TrpV1-expressing neurons in the trigeminal and dorsal root ganglia of mice. Resiniferotoxin (RTX), a potent TrpV1 agonist, administered either by direct injection in the ganglion or intrathecally killed approximately 70% of TrpV1 cells and resulted in modest thermal analgesia. Interestingly, after carageenan injection in the hind paw, the analgesic effects of RTX were dramatically increased with mice now paradoxically showing far less response to heat applied at sites of inflammation. This additional carageenan and RTX-induced analgesia was transient, lasting less than 2 days, and likely resulted from deafferentation of remaining TrpV1 neurons. Remarkably, although RTX affected sensitivity to heat, mechanical sensitivity (both of normal and inflamed tissue) was completely unaltered by toxin-mediated silencing of the TrpV1 sensory input. Thus, our data demonstrate that TrpV1 neurons are selectively tuned nociceptors that mediate responses to thermal but not mechanical pain and insinuate a labeled line model for somatosensory coding.
Molecular Genetics Unit, Laboratory of Sensory Biology, NIDCR, NIH Building 49, Room 1A16, 49 Convent Drive, Bethesda, MD 20892, USA.
Santosh K
SK
Mishra
Mark A
MA
Hoon
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009149:Mustard Plant; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D010938:Plant Oils / Q000494:pharmacology; D018689:Sensory System Agents / Q000494:pharmacology; D013314:Stress, Mechanical; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology*; D014276:Trigeminal Nerve / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D004224:Diterpenes; D010938:Plant Oils; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C024353:resiniferatoxin; D002211:Capsaicin; C027793:mustard oil