PP1318 - Exploring the Pathology of Sensorineural Hearing Loss from Methadone Treatment in Mice

Methadone maintenance treatment (MMT) is a key component of many successful approaches to managing opioid use disorder (OUD). With the goal of lifelong recovery, a holistic approach to patients’ health should consider all consequences of treatment that could affect the health of the patient. It is currently unknown if or how MMT is injuring the cochlea and causing hearing loss. This study models a standard MMT protocol in mice to analyze potential for hearing loss and underlying cochlear histopathology. This work serves to begin informing the clinical audiology community about this unique, under-served patient population.

Summary:

The opioid substance use disorder (OUD) epidemic has expanded over the last several years, and there is a continued need to develop effective strategies to aid in breaking addiction and facilitating long-term recovery.  For over 40 years, methadone has been used as a key pharmacological component of therapies designed to treat OUD.  Methadone is a synthetic opioid agonist that eliminates withdrawal symptoms and can relieve drug cravings by acting on the same opioid receptors in the brain that other opioids activate (NIH, 2018). For proper efficacy, individual patients can require months-to-years of MMT. Long-term MMT treatment can create sensorineural hearing loss that affects the high frequencies of the human audibility range. This is particularly concerning when considering the long-term hearing health of the MMT patient, as early sensorineural hearing loss in young adulthood or middle age can predispose people to more severe hearing difficulties later in life. Therefore, patients who have completed MMT may be in a risk pool for hearing problems in the future. The nature of these hearing problems depends on the underlying pathology in the auditory system. Once we understand the auditory injury, we can counsel and treat these patients effectively in order to conserve their hearing and maximize their communication ability as they proceed on their lifelong recovery. There are currently no articles in the literature that have modeled long-term MMT in animals to assess hearing loss, so we created a mouse model of long-term MMT and performed a battery of physiologic and anatomical assays. Our objective with this study was to measure changes in auditory physiology and cochlear anatomy during long-term MMT. We hypothesized that MMT would cause relatively mild threshold shifts in the ABR and DPOAEs in the high frequencies and would cause IHC synaptopathy in the middle frequencies. We dosed CBA/CaJ mice daily with methadone by oral gavage for nine months, with physiologic hearing testing (ABR thresholds and input-output amplitude measurements, DPOAEs completed at regular intervals. 

Through the first six months of dosing, the mice showed slight threshold shifts (5-15 dB) at multiple frequencies, but the MMT-exposed mice’s threshold shifts were not significantly different from the control mice that received water instead of MMT.  As the MMT progresses, some animals’ thresholds shifted more substantially than others, indicating that auditory sensitivity to MMT might vary across subjects.  Further investigations are needed to determine what, if any, injury patterns can be most reasonably expected in human MMT patients.