Vanilloid Receptors in Hearing: Altered Cochlear Sensitivity by Vanilloids and Expression of TRPV1 in the Organ of Corti

1 Oregon Hearing Research Center, Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University Portland, Oregon 97239; 2 Department of Otolaryngology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031 People's Republic of China; 3 Department of Otolaryngology, Chonbuk National University Medical School, Chonju, Chonbuk, 561-712 Korea; 4 Department of Otolaryngology, Albert Szent-Gyorgyi Medical University, H-6724 Szeged, Hungary; and 5 Kresge Hearing Research Institute, The University of Michigan, Ann Arbor, Michigan 48109-0506 Capsaicin, the vanilloid that selectively activates vanilloid receptors (VRs) on sensory neurons for noxious perception, has been reported to increase cochlear blood flow (CBF). VR-related receptors have also been found in the inner ear. This study aims to address the question as to whether VRs exist in the organ of Corti and play a role in cochlear physiology. Capsaicin or the more potent VR agonist, resiniferatoxin (RTX), was infused into the scala tympani of guinea pig cochlea, and their effects on cochlear sensitivity were investigated. Capsaicin (20 µM) elevated the threshold of auditory nerve compound action potential and reduced the magnitude of cochlear microphonic and electrically evoked otoacoustic emissions. These effects were reversible and could be blocked by a competitive antagonist, capsazepine. Application of 2 µM RTX resulted in cochlear sensitivity alterations similar to that by capsaicin, which could also be blocked by capsazepine. A desensitization phenomenon was observed in the case of prolonged perfusion with either capsaicin or RTX. Brief increase of CBF by capsaicin was confirmed, and the endocochlear potential was not decreased. Basilar membrane velocity (BM) growth functions near the best frequency and BM tuning were altered by capsaicin. Immunohistochemistry study revealed the presence of vanilloid receptor type 1 of the transient receptor potential channel family in the hair cells and supporting cells of the organ of Corti and the spiral ganglion cells of the cochlea. The results indicate that the main action of capsaicin is on outer hair cells and suggest that VRs in the cochlea play a role in cochlear homeostasis. Address for reprint requests: A. L. Nuttall, Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., NRC04, Portland, OR 97239 (E-mail: nuttall{at}ohsu.edu ).