Mechanisms of Mechanisms of tinnitus generationtinnitus generation

Carol A. BauerCurrent Opinion in Otolaryngology & Hea

d and Neck Surgery 2004,12:413–417

R1 石堅

IntroductionIntroductionTinnitus: auditory sensation without external stimulus.

6~20%, (1~3% interferes with daily life)

Theories of tinnitus pathophysiology aberrant peripheral neural activitycentral neural sourcescentral dysfunction + peripheral source of abnormal input

More than one physiologic mechanism

Peripheral sources of Peripheral sources of tinnitustinnitus

Hair cell damage stereocilia decoupling from tectorial membrane noise↑ from molecular motion within the hair cells tinnitusBaseline deviation from random activity of auditory nerve in the absence of stimulation

High-rate pulsatile electrical stimulation to the cochlea suppression of tinnitus (5/11)

Loss of tonic random afferent input loss of inhibition within brainstem auditory structures

Central sources of tinnitusComplete eighth nerve section: normal

Peripheral injury central changesacute (acoustic trauma) / slowly progressive hearing loss.

Inhibition↓ / excitation↑: dorsal cochlear nucleus, inferior colliculusComplex change in glutamatergic transmitter release in ipsilateral cochlear nucleus after noise exposure.

Initially: damaged hair cells, neural fibers degenerated acute↑ in glutamatergic release2 weeks later: glutamatergic release↓ and uptake ↓90 days later: long-term↑of residual glutamatergic synapses

Plasticity and tinnitusNeural plasticity: long-term alterations in central neural function after peripheral sensory receptor damage

Bidirectional information modulation within auditory pathway: corticofugal / corticopetal projections between auditory cortex and brainstem nuclei

Disturbing tinnitus: fail to develop the normal habituation in response to a repetitive non-informative sound.

Auditory enrichment or sound therapy: long-term exposure to low-level (15 dB SPL) sound

Plasticity and tinnitusTinnitus maladaptive cortical reorganizati≒on (ex: phantom limb pain)

Magnetoencephalography: subjective tinnitus loudness / frequency primary auditory cortex.

Psychophysical training with frequency discrimination task plastic changes in cortical representation of a range of frequencies

Exposure to continuous low-level background sound (auditory enhancement) shift in loudness judgments

Somatosensory / vascular factorsElectrical excitation of median nerve somatosensory system modulate the characteristics and loudness of tinnitus.

PET imaging: orofacial maneuvers (jaw clenching) changes in blood flow in temporal lobe / hippocampus modulation of tinnitus loudness.

Injury to head / neck brainstem somatosensory nuclei inappropriate excitation of auditory pathway (dorsal cochlear nucleus) craniocervical tinnitus

Somatosensory / vascular factorsCochlear implants: isometric movements of head, neck, or jaw muscles 50~80% change in tinnitus loudness

Trigeminal ganglion excitatory and inhibitory projections synapse within ventral and dorsal cochlear nucleus

Stimulate trigeminal ganglion 2-deoxyglucose uptake↑ in ipsilateral and contralateral lateral lemniscus and inferior colliculus

Guinea pig: capsaicin trigeminal control of cochlear blood flow

Capsaicin: agonist of type 1 vanilloid receptor (VR-1), nonselective cation channel in small- to medium- diameter primary afferents in the somatosensory system.

Somatosensory / vascular factors

Immunoreactive fibers: trigeminal origin.electrical stimulation of trigeminal ganglion plasma extravasation from cochlear vessels.inflammatory conditions exacerbate tinnitus.

Spiral and vestibular ganglia of rats: VR-1 and 5-lipoxygenase.

tinnitus generation by aspirin and nonsteroidal ototoxicity.

ConclusionConclusionTinnitus appears to be significantly affected in complex ways by somatosensory, limbic, and motor influences.

Effective treatments will certainly emerge from these new areas of research.