title: Noise-induced hearing loss: Neuropathic pain via Ntrk1 signaling.
abstract: Severe noise-induced damage to the inner ear leads to auditory nerve fiber degeneration thereby reducing the neural input to the cochlear nucleus (CN). Paradoxically, this leads to a significant increase in spontaneous activity in the CN which has been linked to tinnitus, hyperacusis and ear pain. The biological mechanisms that lead to an increased spontaneous activity are largely unknown, but could arise from changes in glutamatergic or GABAergic neurotransmission or neuroinflammation. To test this hypothesis, we unilaterally exposed rats for 2h to a 126dB SPL narrow band noise centered at 12kHz. Hearing loss measured by auditory brainstem responses exceeded 55dB from 6 to 32kHz. The mRNA from the exposed CN was harvested at 14 or 28days post-exposure and qRT-PCR analysis was performed on 168 genes involved in neural inflammation, neuropathic pain and glutamatergic or GABAergic neurotransmission. Expression levels of mRNA of Slc17a6 and Gabrg3, involved in excitation and inhibition respectively, were significantly increased at 28days post-exposure, suggesting a possible role in the CN spontaneous hyperactivity associated with tinnitus and hyperacusis. In the pain and inflammatory array, noise exposure upregulated mRNA expression levels of four pain/inflammatory genes, Tlr2, Oprd1, Kcnq3 and Ntrk1 and decreased mRNA expression levels of two more genes, Ccl12 and Il1β. Pain/inflammatory gene expression changes via Ntrk1 signaling may induce sterile inflammation, neuropathic pain, microglial activation and migration of nerve fibers from the trigeminal, cuneate and vestibular nuclei into the CN. These changes could contribute to somatic tinnitus, hyperacusis and otalgia.
authors.affiliation: Center for Hearing & Deafness, State University of New York at Buffalo, Buffalo, NY 14214, United States. Electronic address: smanohar@buffalo.edu.
authors.forename: Senthilvelan
authors.initials: S
authors.lastname: Manohar
authors.affiliation: Center for Hearing & Deafness, State University of New York at Buffalo, Buffalo, NY 14214, United States.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Dahar
authors.affiliation: Center for Hearing & Deafness, State University of New York at Buffalo, Buffalo, NY 14214, United States.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Adler
authors.affiliation: Center for Hearing & Deafness, State University of New York at Buffalo, Buffalo, NY 14214, United States.
authors.forename: Ding
authors.initials: D
authors.lastname: Dalian
authors.affiliation: Center for Hearing & Deafness, State University of New York at Buffalo, Buffalo, NY 14214, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
mesh_terms: D000818:Animals; D017626:Cochlear Nucleus / Q000378:metabolism* / Q000503:physiopathology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D051659:KCNQ3 Potassium Channel; C496918:Kcnq3 protein, rat; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D017465:Receptors, Opioid, delta; C493475:Slc17a6 protein, rat; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D050599:Vesicular Glutamate Transport Protein 2; D020917:Receptor, trkA
keywords: Cochlear nucleus; GABA; Gene array; Glutamate; Neuropathic pain; Noise exposure; Sterile inflammation