Endogenous dynorphins, glutamate and N-methyl-d-aspartate (NMDA) receptors may participate in a stress-mediated Type-I auditory neural exacerbation of tinnitus

Tony L. Sahley, Michael D. Hammonds, Frank Musiek

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Tinnitus is the phantom perception of sounds occurring in the absence of an external auditory stimulus. Tinnitus: [1] effects 50 million individuals, [2] often results from acoustic trauma and, [3] is very often exacerbated under stressful conditions. Tinnitus may result from lesions occurring at any location in the auditory system, but its mechanisms are poorly understood. Evidence is provided supporting an endogenous dynorphin-mediated potentiation of glutamate excitotoxicity at cochlear Type-I auditory dendrites that may well exacerbate chronic subjective neural-generated tinnitus during periods of heightened stress. The proposed mechanism is based on the following: [1] lateral efferent olivocochlear (LEOC) axon terminals contain endogenous dynorphin neuromodulators and are presynaptic to cochlear Type-I auditory dendrites that bear both κ-opioid and N-methyl-d-aspartate (NMDA) receptors/binding sites; [2] the release of presynaptic LEOC dynorphins is likely to be triggered by sympathetic stress via the locus coeruleus; [3] sodium salicylate induces an acute excitotoxicity by potentiating glutamate neurotransmitter effects at cochlear NMDA receptors, resulting in a Type-I auditory neural-generated tinnitus; [4] dynorphins participate in central NMDA-receptor-mediated excitotoxic inflammation; and [5] κ-opioid receptor ligands also modulate Type-I auditory neural activity by potentiating glutamate at cochlear NMDA receptors. A stress-activated release of dynorphins into the cochlea could potentiate the already excitotoxic effects of glutamate, producing: [1] hyperacusis, together with an acute exacerbation of [2] chronic aberrant Type-I neural activity and [3] a worsening of the activity-dependent central auditory neural plasticity changes that must certainly generate the perception of tinnitus. Treatment options are discussed.

Original languageEnglish (US)
Pages (from-to)80-108
Number of pages29
JournalBrain Research
Volume1499
DOIs
StatePublished - Mar 7 2013
Externally publishedYes

Fingerprint

Dynorphins
Tinnitus
Cochlea
Glutamic Acid
Dendrites
Neurotransmitter Agents
Hyperacusis
Sodium Salicylate
Noise-Induced Hearing Loss
Neuronal Plasticity
Locus Coeruleus
Presynaptic Terminals
Opioid Receptors
Opioid Analgesics
aspartic acid receptor
Binding Sites
Ligands
Inflammation

Keywords

  • Dynorphins
  • Glutamate excitotoxicity
  • Lateral efferent olivocochlear (LEOC) system
  • NMDA receptors
  • Stress
  • Tinnitus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Endogenous dynorphins, glutamate and N-methyl-d-aspartate (NMDA) receptors may participate in a stress-mediated Type-I auditory neural exacerbation of tinnitus. / Sahley, Tony L.; Hammonds, Michael D.; Musiek, Frank.

In: Brain Research, Vol. 1499, 07.03.2013, p. 80-108.

Research output: Contribution to journalArticle

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abstract = "Tinnitus is the phantom perception of sounds occurring in the absence of an external auditory stimulus. Tinnitus: [1] effects 50 million individuals, [2] often results from acoustic trauma and, [3] is very often exacerbated under stressful conditions. Tinnitus may result from lesions occurring at any location in the auditory system, but its mechanisms are poorly understood. Evidence is provided supporting an endogenous dynorphin-mediated potentiation of glutamate excitotoxicity at cochlear Type-I auditory dendrites that may well exacerbate chronic subjective neural-generated tinnitus during periods of heightened stress. The proposed mechanism is based on the following: [1] lateral efferent olivocochlear (LEOC) axon terminals contain endogenous dynorphin neuromodulators and are presynaptic to cochlear Type-I auditory dendrites that bear both κ-opioid and N-methyl-d-aspartate (NMDA) receptors/binding sites; [2] the release of presynaptic LEOC dynorphins is likely to be triggered by sympathetic stress via the locus coeruleus; [3] sodium salicylate induces an acute excitotoxicity by potentiating glutamate neurotransmitter effects at cochlear NMDA receptors, resulting in a Type-I auditory neural-generated tinnitus; [4] dynorphins participate in central NMDA-receptor-mediated excitotoxic inflammation; and [5] κ-opioid receptor ligands also modulate Type-I auditory neural activity by potentiating glutamate at cochlear NMDA receptors. A stress-activated release of dynorphins into the cochlea could potentiate the already excitotoxic effects of glutamate, producing: [1] hyperacusis, together with an acute exacerbation of [2] chronic aberrant Type-I neural activity and [3] a worsening of the activity-dependent central auditory neural plasticity changes that must certainly generate the perception of tinnitus. Treatment options are discussed.",
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