Contribution of TRPV1 to the bradykinin-evoked nociceptive behavior and excitation of cutaneous sensory neurons.
Bradykinin (BK), a major inflammatory mediator, excites and sensitizes nociceptor neurons/fibers, thus evoking pain and hyperalgesia. The cellular signaling mechanisms underlying these actions have remained unsolved, especially in regard to the identity of channels that mediate acute excitation. Here, to clarify the contribution of transient receptor potential vanilloid 1 (TRPV1), a heat-sensitive ion channel, to the BK-evoked nociceptor excitation and pain, we examined the behavioral and physiological BK-responses in TRPV1-deficient (KO) mice. A nocifencive behavior after BK injection (100 pmol/site) into mouse sole was reduced in TRPV1-KO mice compared with wild-type (WT). A higher dose of BK (1 nmol/site), however, induced the response in TRPV1-KO mice indistinguishable from that in the WT. BK-evoked excitation of cutaneous C-fibers in TRPV1-KO mice was comparable to that in WT. BK clearly increased intracellular calcium in cultured dorsal root ganglion (DRG) neurons of TRPV1-KO mice, although the incidence of BK-sensitive neurons was reduced. BK has been reported to activate TRPA1 indirectly, yet a considerable part of BK-sensitive DRG neurons did not respond to a TRPA1 agonist, mustard oil. These results suggest that BK-evoked nociception/nociceptor response would not be simply explained by activation of TRPV1 and A1, and that BK-evoked nociceptor excitation would be mediated by several ionic mechanisms.
Katanosaka
Kimiaki
K
Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
Banik
Ratan Kumar
RK
Giron
Rocio
R
Higashi
Tomohiro
T
Tominaga
Makoto
M
Mizumura
Kazue
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000523:psychology*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000294:innervation; D050916:TRPV Cation Channels / Q000235:genetics / Q000502:physiology*
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D001920:Bradykinin; D002118:Calcium