Endogenous dynorphins: possible role in peripheral tinnitus.
Tinnitus has been defined as the perceptual correlate of altered spontaneous neural activity occurring without an external auditory stimulus. Hyperacusis, defined as a collapse of tolerance to sound, is present in 40-86% of those who suffer from disabling forms of tinnitus. Both phenomena often are induced or exacerbated by physical or psychological stress. Biological systems known to regulate the body's overall response to stress use and release endogenous neuroactive opioid peptides. These stress-related neuromodulators consist of products derived from three genetically distinct precursor hormones. Two of these precursor hormones are proenkephalin and prodynorphin. Enkephalin and dynorphin-related peptides exist within the efferent olivocochlear systems (lateral and medial) of several mammalian species, including humans. Prodynorphin derivatives, however, may be restricted exclusively to lateral efferent neurons. Descending lateral efferent axons terminate solely on primary (type I) auditory dendrites innervating cochlear inner hair cells in most species. This action indicates that they play an important role in modulating auditory nerve sensitivity and spontaneous discharge. In a fashion similar to that exhibited by the observed excitatory mechanism of action of dynorphins in the spinal cord, sodium salicylate (aspirin) recently was shown to facilitate the excitatory effects of glutamate in the cochlea. This article provides support for a neurochemical model in which endogenous dynorphins may induce hyperacusis and can contribute to the induction, maintenance, or exacerbation of tinnitus in the auditory periphery by altering auditory type I neural excitability to glutamate.
Sahley
T L
TL
Departments of Speech and Hearing, and Biology, Cleveland State University, Cleveland OH 44115, USA. t.sahley@popmail.csuohio.edu
Nodar
R H
RH
Musiek
F E
FE
D003051:Cochlea / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D006801:Humans; D009847:Olivary Nucleus / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D014012:Tinnitus / Q000150:complications / Q000209:etiology* / Q000378:metabolism*
D004723:Endorphins; D004745:Enkephalins; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D004399:Dynorphins