Is auditory neural hypersensitivity induced by activation of vanilloid receptor (subtype 1, VR1) in the inner ear?

摘要

This study examined whether the activation of the vanilloid receptor, VRI, recently found in nerve cells of the inner ear, can affect auditory neural activity. Consecutive perfusions of the hearing organ with capsaicin (CAP, a VR1 agonist) of several concentrations were employed in an effort to activate VR1 and to characterize dose response while recording spontaneous and sound-elicited electrical activity from the cochlear (auditory) portion of the inner ear. Ensemble background activity (EBA, spectrum of the spontaneous electrical activity recordable in the vicinity of neural and sensory/hair cells of the cochlea) was recorded. Results of ancillary experiments confirmed the predominantly neural origin of an EBA peak around 900 Hz but hair cell origin of a peak roughly around 3000 Hz. However, the EBA appeared to be sensitive to the preparation, expressed in variability of both “neural” and “hair cell” spectral peaks. The hair-cell receptor potentials (cochlear microphonics) also were reduced by both CAP and co-application of CAP and capsazepine (CZP, a VR1 antagonist). Capsaicin induced a dose-dependent increase in the 900-Hz peak ratio (value normalized to overall EBA), as well as in the adjusted 900-Hz peak level (effectively, power around 900-Hz normalized to that around 3000-Hz, i.e. to compensate for a putative receptor cell bias). Increased power, per se, at 900 Hz also was evident in a minority of subjects. This effect appeared to be blocked with perfusion of CZP/CAP, supporting the hypothesis that activation of VR1 induces increased background activity in auditory neurons. Effects of CAP on sound-evoked activity proved more complex but were suggestive of overall depression of the whole-nerve action potential. The CZP/CAP perfusion also appeared to be depressive. Although it is somewhat tenuous to tease out neural from receptor effects of perfusion from results of this study, preliminary findings for some conditions suggest possible specific effects, including changes of latency of the action potential showing an “inverted U” dose response under CAP perfusion and dose-dependent increase with CZP/CAP. The results of the study thus indicate an action of capsaicin on the auditory nerve and support the notion functional significance for VR1 in the peripheral auditory system.