title: Therapeutic effect of sildenafil on blast-induced tinnitus and auditory impairment.
abstract: Blast-induced tinnitus, along with associated auditory impairment and traumatic brain injury, is a primary concern facing military service members. To search for treatment, we investigated the therapeutic effects of sildenafil, a phosphodiesterase-5 inhibitor, given its vasodilatory effects and evidence suggesting its beneficial effects on noise-induced hearing loss. Rats were subjected to three consecutive blast exposures at 22 psi and were monitored for tinnitus using a gap-detection acoustic startle reflex paradigm. Hearing thresholds and detection were tested using auditory brainstem responses and prepulse inhibition, respectively. Blasted rats were either treated with sildenafil or tap water following blast exposure, while age-matched sham control rats were treated with sildenafil and no blast exposure. Our results showed that sildenafil did not effectively prevent acute tinnitus onset and hearing impairment. Instead, sildenafil significantly suppressed high-frequency tinnitus from 3 to 6 weeks after blast exposure and reduced hearing impairment during the first week after blast exposure. Complex results were observed in the startle force data, where sildenafil-treated rats displayed significantly reduced startle force compared to the untreated blasted group, suggesting possible mitigation of traumatic brain injury and suppression of hyperacusis-like percepts. Taken together, sildenafil showed a therapeutic effect on blast-induced tinnitus and audiological impairment in a time-dependent manner. Other regimens such as higher dosage prior to blast exposure and combination with other treatments deserve further investigation to optimize the therapeutic effects.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: G
authors.initials: G
authors.lastname: Mahmood
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Mei
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hojjat
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: E
authors.initials: E
authors.lastname: Pace
authors.affiliation: Department of Biomedical Engineering, Wayne State University College of Engineering, Detroit, MI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kallakuri
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, MI, USA; Department of Communication Sciences & Disorders, Wayne State University College of Liberal Arts & Sciences, Detroit, MI, USA. Electronic address: jinzhang@med.wayne.edu.
authors.forename: J S
authors.initials: JS
authors.lastname: Zhang
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D001753:Blast Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D007839:Functional Laterality; D034381:Hearing Loss / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology; D011687:Purines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013997:Time Factors; D014012:Tinnitus / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
keywords: blast; hyperacusis; rat; sildenafil (Viagra, Revatio); tinnitus; traumatic brain injury