Hypotonicity Induces TRPV4-Mediated Nociception in Rat

• Published in: Neuron (Cambridge, Mass.) Vol. 39; no. 3; pp. 497 - 511
• Main Authors: Alessandri-Haber, Nicole, Yeh, Jenny J, Boyd, Aileen E, Parada, Carlos A, Chen, Xiaojie, Reichling, David B, Levine, Jon D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.07.2003; Elsevier Limited
• Subjects: Afferent Pathways - drug effects; Afferent Pathways - metabolism; Animals; Base Sequence; Cation Transport Proteins; Cricetinae; Extracellular Space - drug effects; Extracellular Space - physiology; Hypotonic Solutions; Ion Channels - antagonists & inhibitors; Ion Channels - physiology; Kinases; Male; Molecular Sequence Data; Neurons; Neurons - drug effects; Neurons - metabolism; Osmolar Concentration; Pain Measurement - drug effects; Pain Measurement - methods; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Studies; TRPV Cation Channels
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(03)00462-8

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 E 2. This osmotransduction causes nociception, since administration of a small osmotic stimulus into skin sensitized by PGE 2 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.