Hypotonicity induces TRPV4-mediated nociception in rat.
We hypothesized that TRPV4, a member of the transient receptor family of ion channels, functions as a sensory transducer for osmotic stimulus-induced nociception. We found that, as expected for a transducer molecule, TRPV4 protein is transported in sensory nerve distally toward the peripheral nerve endings. In vivo single-fiber recordings in rat showed that hypotonic solution activated 54% of C-fibers, an effect enhanced by the hyperalgesic inflammatory mediator prostaglandin E2. This osmotransduction causes nociception, since administration of a small osmotic stimulus into skin sensitized by PGE2 produced pain-related behavior. Antisense-induced decrease in expression of TRPV4 confirmed that the channel is required for hypotonic stimulus-induced nociception. Thus, we conclude that TRPV4 can function as an osmo-transducer in primary afferent nociceptive nerve fibers. Because this action is enhanced by an inflammatory mediator, TRPV4 may be important in pathological states and may be an attractive pharmacological target for the development of novel analgesics.
Alessandri-Haber
Nicole
N
Division of Neuroscience, University of California, San Francisco, San Francisco, California 94143, USA.
Yeh
Jenny J
JJ
Boyd
Aileen E
AE
Parada
Carlos A
CA
Chen
Xiaojie
X
Reichling
David B
DB
Levine
Jon D
JD
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins; D006224:Cricetinae; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D007038:Hypotonic Solutions; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009994:Osmolar Concentration; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels
D027682:Cation Transport Proteins; D007038:Hypotonic Solutions; D007473:Ion Channels; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat