A Phenotypic Comparison of Loudness and Pain Hyperacusis: Symptoms, Comorbidity, and Associated Features in a Multinational Patient Registry

Abstract

Purpose: Hyperacusis is a complex and poorly understood auditory disorder characterized by decreased tolerance to sound at levels that would not trouble most individuals. Recently, it has been suggested that individuals who experience otalgia in response to everyday sounds (termed “pain hyperacusis”) may differ clinically from those whose primary symptom is the perception of everyday sounds as excessively loud (termed “loudness hyperacusis”). Despite this theoretical distinction, there have been no empirical studies directly comparing these two populations of hyperacusis patients.

Method: Using data from a multinational patient registry (the Coordination of Rare Diseases at Sanford [CoRDS] Registry), we examined self-reported demographics, symptoms, comorbidity, and response to treatment in a sample of 243 adults with hyperacusis, 152 of whom were classified as having pain hyperacusis based on reported symptoms. Bayesian statistical tests were used to investigate both the presence and absence of group differences between patients with loudness and pain hyperacusis.

Results: Individuals with pain hyperacusis presented with a more severe clinical phenotype, reporting a higher frequency of temporary symptom exacerbations (i.e., “setbacks”), less perceived symptom improvement over time, more severe comorbid headache disorders, and reduced benefit from sound therapy. However, the two hypothesized hyperacusis subtypes exhibited more similarities than differences, with the majority of symptoms and comorbidities being equally prevalent across groups. Multiple comorbidities were commonly observed, including tinnitus, primary headache disorders, psychiatric disorders, and functional somatic syndromes. Intolerance of sensory stimuli in other modalities was also frequently reported.

Conclusion: Although this study provides little evidence that loudness and pain hyperacusis are pathophysiologically distinct conditions, our findings indicate that a pain-predominant phenotype may be a meaningful prognostic marker in patients with hyperacusis.

Full text

AJA
Research Article
A Phenotypic Comparison of Loudness
and Pain Hyperacusis: Symptoms,
Comorbidity, and Associated Features
in a Multinational Patient Registry
Zachary J. Williams,
a,b,c,d
Evan Suzman,
e
and Tiffany G. Woynaroski
b,c,d,f
Purpose:AQ1 Hyperacusis is a complex and poorly understood
auditory disorder characterized by decreased tolerance to
sound at levels that would not trouble most individuals.
Recently, it has been suggested that individuals who
experience otalgia in response to everyday sounds (termed
pain hyperacusis)maydifferclinicallyfromthosewhoseprimary
symptom is the perception of everyday sounds as excessively
loud (termed loudness hyperacusis). Despite this theoretical
distinction, there have been no empirical studies directly
comparing these two populations of hyperacusis patients.
Method: Using data from a multinational patient registry (the
Coordination of Rare Diseases at Sanford Registry), we
examined self-reported demographics, symptoms, comorbidity,
and response to treatment in a sample of 243 adults with
hyperacusis, 152 of whom were classified as having pain
hyperacusis based on reported symptoms. Bayesian
statistical tests were used to investigate both the presence
and absence of group differences between patients with
loudness and pain hyperacusis.
Results: Individuals with pain hyperacusis presented
with a more severe clinical phenotype, reporting a higher
frequency of temporary symptom exacerbations (i.e.,
“setbacks”), less perceived symptom improvement over
time, more severe comorbid headache disorders, and
reduced benefit from sound therapy. However, the two
hypothesized hyperacusis subtypes exhibited more
similarities than differences,withthemajorityofsymptoms
and comorbidities being equally prevalent across
groups. Multiple comorbidities were commonly observed,
including tinnitus, primary headache disorders, psychiatric
disorders, and functional somatic syndromes. Intolerance
of sensory stimuli in other modalities was also frequently
reported.
Conclusion: Although this study provides little evidence
that loudness and pain hyperacusis are pathophysiologically
distinct conditions, our findings indicate that a pain-
predominant phenotype may be a meaningful prognostic
marker in patients with hyperacusis.
Hyperacusis is a hearing disorder characterized by
decreased tolerance to sound at levels that would
not trouble most people (Fackrell et al., 2019).
Individuals experiencing hyperacusis report that everyday
sounds are perceived as excessively loud, intense, fright-
ening, overwhelming, or physically painful, and can trig-
ger additional physical symptoms, leading to significant
distress and functional impairment (Ke et al., 2020; Tyler
et al., 2014). This condition is distinct from misophonia
(an aversive reaction to specific “trigger”sounds charac-
terized by anger, extreme annoyance, and disgust) and
phonophobia (a persistent, abnormal, and unwarranted
fear of certain sounds), although these other forms of de-
creased sound tolerance can co-occur with hyperacusis
a
Medical Scientist Training Program, Vanderbilt University School of
Medicine, Nashville, TN
b
Department of Hearing and Speech Sciences, Vanderbilt University
Medical Center, Nashville, TN
c
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN
d
Frist Center for Autism and Innovation, Vanderbilt University,
Nashville, TN
e
Graduate Program in Biomedical Sciences, Vanderbilt University,
Nashville, TN
f
Vanderbilt Kennedy Center, Vanderbilt University Medical Center,
Nashville, TN
Correspondence to Zachary J. Williams:
Zachary.j.williams@vanderbilt.edu
Editor-in-Chief: Ryan W. McCreery
Editor: Jamie Bogle
Received December 4, 2020
Revision received January 23, 2021
Accepted January 26, 2021
https://doi.org/10.1044/2021_AJA-20-00209
Disclosure: Zachary J. Williams has received consulting fees from Roche. He
also owns stock and stock options in Axsome Therapeutics, Inc., CRISPR
Therapeutics AG, and Editas Medicine. The other authors have declared that no
other competing interests existed at the time of publication. No funding body or
source of support had a role in the study design, data collection, analysis, or
interpretation, decision to publish, or preparation of this article.
American Journal of Audiology •1–18 •Copyright © 2021 American Speech-Language-Hearing Association 1
AJA-20-00209Williams (Author Proof )

(Jastreboff & Jastreboff, 2015). Although prevalence esti-
mates of hyperacusis are varied and highly method depen-
dent, an estimated 5.9% of U.S. adults report problems
tolerating everyday sounds based on data from the 2014
National Health Interview Survey (Zelaya et al., 2015), and
self-reported sound intolerance was endorsed by 9% of adults
in a large Swedish study (Paulin et al., 2016). Hyperacusis
is also associated with a range of other disorders, including
tinnitus, hearing impairment, traumatic brain injury, mi-
graine, anxiety disorders, mood disorders, autism spectrum
disorder, and functional somatic syndromes such as fibro-
myalgia and irritable bowel syndrome (Assi et al., 2018;
Cederroth et al., 2020; Paulin et al., 2016; Sheldrake et al.,
2015; Williams, He, et al., 2021; Williams, Suzman, &
Woynaroski, 2021). At this time, research on hyperacusis
is still in its infancy; the etiology, pathology, and natural
history of this condition remain poorly understood (Baguley
& Hoare, 2018; Pienkowski et al., 2014; Tyler et al., 2014),
and no evidence-based recommendations currently exist to
guide its diagnosis or treatment.
One recent approach to the study of hyperacusis has
been dividing the condition into subtypes based on the spe-
cific aversive reactions to sounds that patients experience.
In their seminal review, Tyler et al. (2014) proposed that
hyperacusis could be separated into four subtypes: loud-
ness hyperacusis, pain hyperacusis, annoyance hyperacusis,
and fear hyperacusis, occurring either separately or in com-
bination. Though many researchers consider misophonia
(i.e., Tyler’s“annoyance hyperacusis”) and phonophobia
(i.e., Tyler’s“fear hyperacusis”) to be separate conditions
from hyperacusis (Fackrell et al., 2019; Fagelson & Baguley,
2018; Jastreboff & Jastreboff, 2015), the more narrowly de-
fined hyperacusis can still be subdivided into loudness and
pain subtypes. For individuals with loudness hyperacusis,
the threshold for loudness discomfort is reduced, and sounds
of moderate intensity are judged to be very loud (Phillips
& Carr, 1998). These symptoms are associated with distur-
bances of loudness perception, as evidenced by excessive
growth of perceived loudness as a function of sound inten-
sity (Brandy & Lynn, 1995; Hébert et al., 2013; Noreña &
Chéry-Croze, 2007). Pain hyperacusis is a less well-understood
form of the condition in which an individual perceives phys-
ical pain in the ear when exposed to certain sounds at levels
far below those needed to cause pain in a typical listener
(i.e., approximately 120 dB SPL). The character of the pain
is variable across individuals (e.g., dull ache, burning, sharp,
stabbing, or throbbing), and patients often report experienc-
ing transient symptom exacerbations in response to certain
sounds, colloquially referred to as “setbacks”(Pollard, 2019).
Although the pathophysiology of pain hyperacusis is still
poorly understood, recent discoveries have implicated the
population of Type II cochlear afferent neurons in the per-
ception of noxious or painful auditory stimuli (Flores et al.,
2015; Liu et al., 2015; Wu et al., 2018). Although specula-
tive, researchers have hypothesized that increased sensitivity
or inappropriate activation of this population of Type II
afferents may mediate the symptoms of pain hyperacusis
(Auerbach, 2019; Noreña et al., 2018). To date, there has
been very little empirical research characterizing the clinical
phenotype of pain hyperacusis, and it remains unclear
whether pain hyperacusis can be meaningfully distinguished
from loudness hyperacusis in terms of clinical severity, nat-
ural history, associated symptoms, comorbidity, or response
to treatment.
Patient self-report is increasingly recognized as an im-
portant modality for assessing the impact of disease states
and generating novel questions for investigation (Acquadro
et al., 2003; Weldring & Smith, 2013). These data are partic-
ularly informative when investigating disorders such as
hyperacusis that are predominantly characterized by sub-
jective symptoms, and large-scale patient surveys have pro-
vided useful insights into several similar conditions (Bennett
et al., 2007; Chu et al., 2018; Kanazawa et al., 2016; Rouw
& Erfanian, 2018). Leveraging an existing database of pa-
tient survey responses (the Coordination of Rare Diseases
at Sanford [CoRDS] Registry; Trudeau, 2013), the current
study was designed to provide an in-depth clinical descrip-
tion of the hyperacusis phenotype, with the specific goal of
examining meaningful differences between loudness and
pain subtypes of the condition. The major aims of this study
were to compare individuals with loudness and pain hypera-
cusis with respect to (a) demographics, background, and on-
set of hyperacusis; (b) quality of life (QoL) and functional
impairment; (c) specific symptoms attributed to hyperacusis;
(d) clinical course and symptom fluctuation (including the
presence and severity of “setbacks”); (e) comorbid condi-
tions; (f) comorbid nonauditory sensory symptoms; and
(g) perceived benefit of interventions such as medication
and sound therapy.
Method AQ2
Study Sample and Data Source
Data for the current study were drawn from a multi-
national hyperacusis patient registry (hereafter the “CoRDS
Registry”) established in 2015 by the nonprofit organization
Hyperacusis Research Limited, Inc. in partnership with San-
ford Research (Pollard, 2019; Trudeau, 2013). Anonymized
data from this repository are available from Sanford Re-
search upon request (see Availability of Data and Materials
section for additional details). For the current study, data
were obtained from the CoRDS Registry in October of
2020. The study protocol for the secondary analysis of
these data was approved by the institutional review board
of Vanderbilt University Medical Center.
At the time of data access, a total of 456 individuals
had provided data for this registry, including both adult
patients with self-reported hyperacusis and parents or
caregivers of minors with hyperacusis. For the current
study, we limited our scope to self-reporting adults, given
the subjective nature of hyperacusis symptoms and the
relatively small number of minors in the sample (n= 18
[3.9%]). Included patients were required to (a) self-report
a diagnosis (including self-diagnosis) of hyperacusis in re-
sponse to the question “Please list all rare disease diagnoses,”
2American Journal of Audiology •1–18
AJA-20-00209Williams (Author Proof )

(b) report symptoms consistent with either loudness or pain
hyperacusis (i.e., everyday sounds are perceived as overly
loud and/or cause physical pain), and (c) provide an answer
to the question, “In the past twelve (12) months, approxi-
mately how often has the Participant experienced pain in one
or both ears?”(response options: “Never,”“Once a month,”
“2–3 times per month,”“Once a week,”“Every day,”and
“Continuously”), which we used to characterize individuals
into the categories of loudness and pain hyperacusis along
with free-text reports of hyperacusis symptomatology. A
total of 249 adults answered the question regarding pain
frequency, and of these, an additional six prospective par-
ticipants were eliminated from the study due to either not
reporting a diagnosis of hyperacusis or reporting no symp-
toms consistent with loudness or pain hyperacusis (i.e., some
patients recorded only strong emotional reactions to sound
[i.e., misophonia] or reactive tinnitus without endorsing
either pain in the ears or the perception of everyday sounds
as excessively loud). Thus, the final sample of participants
analyzed in the current study comprised 243 unique individ-
uals with hyperacusis.
Survey Questions
Participants completed two questionnaires, including
a 79-item background survey completed by patients in all
CoRDS registries and a 90-item hyperacusis-specific survey
designed for this particular registry (full questionnaires avail-
able from CoRDS on request). Analyzed questions from the
background survey included (a) demographic variables (age,
sex, race, ethnicity, country of residence), (b) rare and non–
rare disease diagnoses (free text), (c) symptoms attributed
to hyperacusis (free text), (d) and five items assessing vari-
ous facets of QoL (1. “In general, would the participant say
his/her health is…?”; 2. “Does the participant’s health now
limit him/her in doing vigorous activities? ”; 3. “How much
did pain interfere with the participant’s enjoyment of life?”;
4. “How often does the participant feel tired?”;5.“The partic-
ipant feels depressed….”). Participants responded to these
QoL items using a 5-point Likert scale, with the first ques-
tion rated from “Excellent”to “Poor”and the other four
rated from Never to Always. Item scores were coded such
that higher scores indicated higher QoL (i.e., a response
of “Always”was scored as “1”and a response of “Never”
was scored as “5”).
The hyperacusis-specific questionnaire was com-
posed of four sections: (a) background and onset of hyper-
acusis (e.g., duration of hyperacusis, laterality, symptom
change over time, hyperacusis risk factors), (b) symp-
toms (e.g., perception of everyday sounds as unbearably
loud, pain character and frequency, associated symp-
toms such as pressure and ear fullness, setback frequency
and duration, and degree of functional impairment from
hyperacusis), (c) comorbid conditions (e.g., presence and
characteristics of tinnitus, headache frequency and severity,
additional medical conditions, presence and severity of
sensory intolerance in other modalities), and (d) hyper-
acusis management and treatment (e.g., response to sound
therapy, use of ear protection, perceived benefit from
medications). Specific outcomes analyzed in the current
study and the survey questions used to assess them are de-
tailed in T1Table 1.
Classification of Loudness and Pain Hyperacusis
As part of the hyperacusis-specific survey, participants
answered the following question: “In the past twelve (12)
months, approximately how often has the Participant experi-
enced pain in one or both ears? ”Notably, only 9.5% of our
sample (n= 23) responded “Never”to this question, indi-
cating that the majority of hyperacusis patients do endorse
noise-induced pain at least some of the time. However,
the frequency of pain episodes in the sample varied widely,
with 24.7% of participants (n= 60) endorsing pain once
per week or less, 45.7% (n= 111) endorsing pain daily,
and 20.2% (n= 49) endorsing continuous pain in their ears.
Thus, for an individual to be classified as having pain
hyperacusis, we required that they report ear pain as oc-
curring “Every day”or “Continuously”(n= 160 [65.8%]).
Individuals reporting pain weekly or less were classified
as having loudness hyperacusis. Participants who reported
pain were also surveyed regarding the character of their
pain (with response options of “Dull ache,”“Burning pain,”
“Throbbing pain,”“Sharp pain,”“Stabbing pain,”and
“Other”), and free-text explanations of those who marked
the “Other”response were examined to determine whether
the sensation being described was clearly indicative of
pain. In cases where the free text unambiguously clari-
fied that the sensation was not pain (e.g., the responses “a
nervous panicky reaction”and “A buzzy distortion”), par-
ticipants were removed from the pain hyperacusis group
and classified as having solely loudness hyperacusis. This
process resulted in eight individuals being reclassified as
having loudness hyperacusis rather than pain hyperacusis.
Thus, using this method, 152 individuals in our sample
(62.6%) were classified as having pain hyperacusis, while
91 (37.4%) were classified as having loudness hyperacu-
sis. Notably, those classified as having pain hyperacusis
frequently reported excessive loudness perception, with
over 90% of participants in the pain hyperacusis group
reporting that they find everyday sounds to be “unbear-
ably loud,”as evidenced by affirmative responses to the
question, “Are everyday sounds unbearably loud to the
Participant?”
Coding of Free-Text Responses
In addition to the multiple-choice questions in the
background and hyperacusis-specific surveys, participants
answered several open-ended questions to qualitatively
describe their symptoms (e.g., “Please list symptoms of
rare disease diagnosis”and “List any other primary medical
conditions (disease/condition, autoimmune disorder, cancer,
etc.) that affect the participant”). Open-ended questions were
also included to elaborate on responses of “Other”provided
by participants to questions like “What other types of
Williams et al.: Comparison of Loudness and Pain Hyperacusis 3
AJA-20-00209Williams (Author Proof )

Table 1. Outcomes of interest derived from closed-ended questions on the hyperacusis-specific CoRDS survey.
Outcome Data type Source question Response options n
Pain
n
Loudness
Duration of
hyperacusis
Ordinal How long has the participant had
hyperacusis?
Less than 1 year; 1–3 years;
4–6 years; 7–10 years;
11–14 years; 15+ years
144 87
Sudden onset Binary (yes/no) How did the onset of the condition
start?
Suddenly = yes
Gradually; uncertain = no
143 85
Bilateral symptoms Binary (yes/no) Which ear is affected by hyperacusis? Both = yes;
Left; right = no
149 90
Symmetric symptoms Binary (yes/no) Are both ears equally affected? Yes; no 150 89
Professional diagnosis Binary (yes/no) How was the participant initially
diagnosed?
Audiologist; ENT; medical
doctor = yes
Self; other = no
141 86
Pre-existing hearing loss Binary (yes/no) Does the participant have pre-existing
hearing loss?
Yes; no 152 88
Wears hearing aids Binary (yes/no) Does the participant wear hearing aids? Both ears; left; right; = yes
No
140 83
Head injury Binary (yes/no) Has the participant ever had a serious
head injury (from car accident,
fall, etc.)?
Yes; no 147 88
Loud noise exposure Binary (yes/no) Does the participant have a history
of loud noise exposures?
Yes
No; uncertain = no
150 89
Traumatic noise/blast
exposure
Binary (yes/no) Has the participant had traumatic
impulse noise exposures (blasts,
gun fire, etc.)?
Yes; no 151 90
Delayed pain onset Binary (yes/no) When the participant experienced
ear pain as a result of an event,
how long after the event did the
pain begin?
After a few hours; the next day;
a few days later; weeks
later = yes
Immediately = No
131 57
Duration of pain Ordinal When the participant experiences ear
pain from environmental sounds,
how long does the pain last?
Less than 1 hr; 1–4 hr; 5–24 hr;
several days; several weeks;
several months; more than
several months
128 56
Functional impairment:
occupational
Ordinal Rate the impact of the participant’s
hyperacusis on the participant’s
education/career.
0–10 (10 indicates the participant’s
condition prevents them from
going to school or working)
142 88
Functional impairment:
domestic
Ordinal Rate the impact of the participant’s
hyperacusis on the participant’s
home life.
0–10 (10 indicates the participant’s
condition ruined their home life)
147 89
Functional impairment:
social
Ordinal Rate the impact of the participant’s
hyperacusis on the participant’s
social life.
0–10 (10 indicates the participant’s
condition ruined their social life)
145 89
Symptom change
over time
Categorical Has the severity of the participant’s
hyperacusis changed over time?
Better; worse; fluctuated; same 147 87
Setback severity Ordinal When the participant experiences
a setback, how does the participant’s
condition compare to earlier periods?
Small setback; moderately worse;
worse than it ever was previously
121 69
Setback recovery time Ordinal How long does it take for the participant
to recover from a setback?
Several days; several weeks;
months; years
119 70
Recovery worsened
by sounds
Binary (yes/no) Does the participant’s recovery take
longer if they are exposed to a
louder noise?
Yes; no 120 73
Tinnitus impairs sleep Binary (yes/no) Does the participant have difficulty
sleeping due to their tinnitus?
Yes; no 126 78
Tinnitus impairs
concentration
Binary (yes/no) Does the participant have difficulty
concentrating while reading in a
quiet room due to their tinnitus?
Yes; no 125 78
Reactive tinnitus Binary (yes/no) Do exposure sounds raise the volume
of the participant’s tinnitus?
Yes; no 122 77
Reactive tinnitus
duration
Ordinal If the volume level of the participant’s
tinnitus increases, how long does
the increase in volume last?
Minutes; hours; days; weeks;
permanently
117 68
Headache frequency Ordinal How often does the participant
experience headaches?
Never; rarely; monthly; weekly;
daily
143 88
Headache severity Ordinal How severe are the participant’s
headaches? (10 being the most
severe)
1–10 124 70
(table continues)
4American Journal of Audiology •1–18
AJA-20-00209Williams (Author Proof )

physical sensations does the participant experience along
with hyperacusis?”and “When the participant experiences
ear pain from environmental sounds, what type of pain do
they experience?”
In order to more fully characterize the clinical phe-
notypes of participants in this registry, we examined each
participant’s free-text responses, classifying them according
to the additional sound-evoked symptoms they reported
(e.g., ear fullness, jaw pain, hearing changes). These re-
sponses were categorized into binary variables that indi-
cated whether a specific symptom was mentioned by a given
patient. A similar procedure was undertaken for the ques-
tions regarding additional medical comorbidities and specific
medications that patients found helpful for their hypera-
cusis symptoms. As the presence of certain comorbidities
(e.g., temporomandibular joint disorders [TMJDs] and
tinnitus) could be indicated in a multiple-choice question
or a free-text field, we coded a given condition as present
if it was endorsed by a patient in either location. Binary
variables were created for any symptom category, comor-
bid condition, or medication class that was reported by
5% or more of the sample (n≥12; see below paragraph
for a full list). Notably, as only 84 patients provided a re-
sponse to the question regarding medication benefit, we
created categories for medication classes perceived as ben-
eficial by eight or more individuals (i.e., approximately
10% of the individuals who responded to that question).
In the domain of symptoms, we categorized pain char-
acter into three nonexclusive categories based on the latent
structure of the Short-form McGill Pain Questionnaire
(Dworkin et al., 2009): (a) continuous pain (“throbbing,”
“aching,”“gnawing,”“heavy,”or “tender”); (b) intermit-
tent pain (“stabbing,”“sharp,”“shooting,”“splitting,”
“electric-shock,”and “piercing”); and (c) neuropathic-like
pain (“hot/burning,”“cold/freezing,”“pain caused by light
touch”; note that, while paresthesias are also included in
this section of the Short-form McGill Pain Questionnaire,
we classified such sensations as associated symptoms rather
than pain per se). Participants who described multiple types
of pain in their descriptions were classified in multiple cate-
gories. For participants who described pain but did not re-
spond to the multiple-choice item describing pain character
or provide any descriptors, we considered responses to
the pain character categories to be missing. With regard to
Table 1. (Continued).
Outcome Data type Source question Response options n
Pain
n
Loudness
Headache worsened
by sounds
Binary (yes/no) Does the participant experience
headaches more frequently after
they have been exposed to loud
noises?
Yes; no 122 71.
Vertigo daily/weekly Binary (yes/no) How often does the participant
experience balance problems
(vertigo)?
Never; rarely; monthly = no
Weekly; daily = yes
144 86.
Vertigo severity Ordinal Rate the severity of the participant’s
balance issues (10 being the most
severe).
1–10 90 58.
Vertigo worsened
by sound
Binary (yes/no) Does the participant experience
increased/more frequent balance
issues after they are exposed to
loud noises?
Yes; no 91 57.
Photophobia daily/
weekly
Ordinal How often do bright lights bother
the participant?
Never; rarely; monthly = no
Weekly; daily = yes 141 83
Photophobia severity Ordinal How severely do bright lights bother
the participant? (10 being the
most severe)
1–10
104 61
Osmophobia present Binary (yes/no) Is the participant bothered by strong
smells?
Yes; no
140 81
Tactile intolerance
present
Binary (yes/no) Is the participant bothered by touch? Yes; no
143 85
Duration of sound
therapy
Ordinal How long has the participant
followed/utilized sound therapy
protocol?
Less than 1 year; 1–2 years;
3–4 years; 5–6 years;
7–8 years; 8+ years
88 48
Outcome of sound
therapy
Ordinal How much improvement has the
participant experienced from
following/utilizing sound therapy
protocol?
Worsened hyperacusis;
worsened tinnitus =
worsened symptoms
No improvement; minor improvement;
some improvement; significant
improvement; hyperacusis
is almost eliminated
91 49
Note. Additional outcomes examined were (a) derived from CoRDS background survey, (b) derived from free-text fields, or (c) derived from a
combination of free-text and multiple-choice fields. Number of nonmissing responses determined both by voluntary skipping (e.g., providing
no answer) and survey logic (e.g., severity of headache not rated by individuals not endorsing headaches); n
Pain
/n
Loudness
= number of patients
in pain/loudness hyperacusis group providing nonmissing response to question. CoRDS = Coordination of Rare Diseases at Sanford.
Williams et al.: Comparison of Loudness and Pain Hyperacusis 5
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ancillary symptoms, the following were reported frequently
enough to warrant categorization: pain in face, jaw, and
neck regions; ear fullness; ear pressure; scalp or head pres-
sure; flu-like symptoms (e.g., fatigue, malaise); fluttering/
middle ear myoclonus; hearing changes (e.g., distortion,
saturation, autophony, temporary hearing loss); sounds
such as clicking or popping; and paresthesia (defined broadly,
including numbness, tingling, heat, cold, and vibrotactile
sensations). Comorbidities were classified into the follow-
ing categories: tinnitus, hearing loss, migraine, phonopho-
bia (i.e., a specific phobia of sound, including pronounced
sound-induced anxiety reactions), tension headache, chronic
daily headache of any type, TMJD, bruxism, osteoarthritis,
any anxiety disorder (including posttraumatic stress disor-
der, obsessive–compulsive disorder, and phonophobia), any
unipolar depressive disorder, any psychiatric disorder (in-
cluding misophonia; Jager et al., 2020; Schröder et al., 2013),
and any functional somatic syndrome (defined as the follow-
ing diagnoses: fibromyalgia, myalgic encephalomyelitis/
chronic fatigue syndrome, chronic daily headache, irritable
bowel syndrome, TMJD, multiple chemical sensitivity,
functional neurological [conversion] disorder, interstitial
cystitis/bladder pain syndrome, and whiplash-associated
disorders). Lastly, we created binary variables to represent
perceived benefit from three classes of medications: benzo-
diazepines, opioids, and gabapentinoids.
Statistical Analyses
In order to determine which aspects of the hyperacusis
phenotype differed meaningfully between individuals classi-
fied as having loudness and pain hyperacusis, we compared
values of each outcome of interest between the two groups
in a Bayesian framework. When the outcome of interest was
categorical (e.g., the presence or absence of tinnitus), we ex-
amined group differences using a Bayesian analogue of the
Pearson chi-squared test (Gûnel & Dickey, 1974; Jamil
et al., 2017). When the outcome of interest was a contin-
uous variable (e.g., age), we examined mean differences
using a Bayesian analogue of the Welch (unequal-variances)
ttest (Kruschke, 2013). Lastly, when the outcome of interest
was ordinal (e.g., a Likert scale item), group differences
were assessed using a Bayesian ordered probit regression
model (Bürkner & Vuorre, 2019; Liddell & Kruschke,
2018), which assumes that a normally distributed continu-
ous latent variable underlies each ordinal dependent vari-
able. Additional details on the specifics of each model are
presented later in this section.
Conducting group comparisons in a Bayesian hypoth-
esis testing framework allowed us to quantify evidence both
for or against a given null hypothesis using Bayes factors
(Kass & Raftery, 1995; Ly et al., 2020; Wagenmakers et al.,
2018). When considering an arbitrary null hypothesis (H
0
)
and a mutually exclusive alternative hypothesis (H
1
), the
Bayes factor (BF
10
) is defined as the ratio of how likely the
data are under H
1
divided by how likely the data are under
H
0
. Values of BF
10
greater than 3 are typically considered
to provide substantial evidence for H
1
over H
0
, and values
of BF
10
less than 0.333 are typically considered to provide
substantial evidence for H
0
over H
1
(Wagenmakers et al.,
2011). Values of BF
10
between 0.333 and 3 are typically
considered inconclusive, providing only “anecdotal”evi-
dence for either H
0
or H
1
. Thus, for every group compari-
son, results could be interpreted as (a) providing significant
support for a true group difference on the outcome vari-
able (BF
10
> 3), (b) providing significant support for the ab-
sence of a group difference on the outcome variable (BF
10
<
0.333), or (c) providing inconclusive evidence for or against
a group difference on the outcome variable. With the use
of Bayesian statistics, we are therefore able to characterize
significant differences between groups as well as significant
similarities, allowing for a more nuanced comparison of
loudness and pain hyperacusis relative to more conventional,
frequentist analytic approaches.
All statistical computations were performed in R
(R Core Team, 2020). FN1
1
Categorical variables were compared
between groups using default Gûnel–Dickey Bayes factors
for contingency tables (as implemented in the BayesFactor
R package; Morey & Rouder, 2018) based on the indepen-
dent multinomial sampling scheme (Gûnel & Dickey, 1974;
Jamil et al., 2017). In this test, the number of individuals in
each clinical group (pain hyperacusis and loudness hypera-
cusis) is treated as fixed, and cell counts are multinomially
distributed within each row of the contingency Table. A
Dirichlet prior with parameters a
1
,…,a
k
= 1 is placed on
the parameters of each multinomial distribution, and the
analytically derived Bayes factor provides evidence for or
against the null hypothesis of equivalent distributions be-
tween groups.
For 2 ×2 contingency tables, the Bayes factor for
the independent multinomial sampling plan reduces to a
test for the equality of two proportions (i.e., the odds ratio
[OR]ofendorsementisequalto1).Thus,whengroups
were being compared on binary variables, we additionally
calculated the OR along with its 95% highest-density credi-
ble interval (CrI) using 15,000 Monte Carlo samples from
the joint posterior distribution of the model parameters. For
comparison with a frequentist hypothesis test, group differ-
ences were deemed “statistically significant”when the full
95% CrI excluded OR = 1. Notably, as the null hypothesis
of complete equality between groups is always false at the
population level (Cohen, 1994), we further sought to test
whether the OR was greater than an interval null hypothesis
representing effects that are thought to be too small to be
practically meaningful (Kirk, 1996). This interval, termed
the region of practical equivalence (ROPE; Kruschke &
Liddell, 2018), was defined as the interval OR = [0.905,
1.105] (i.e., values in which log(OR)isbetween−0.1 and
0.1). In order to test the null hypothesis that the popula-
tion effect lies within the ROPE (i.e., the difference in
1
Custom R code to perform statistical analyses can be found on
the ResearchGate profile of the corresponding author (https://www.
rese archgate.net/pro fil e/Zachary_Wil liams19/pu bli cations). The
remainder of research materials can be obtained from the corresponding
author upon request.
6American Journal of Audiology •1–18
AJA-20-00209Williams (Author Proof )

proportions in the population is too small to be of practi-
cal importance), we calculated the ROPE Bayes factor
(BF
ROPE
;Makowskietal.,2019),definedastheoddsof
the prior OR distribution falling within the ROPE divided
by the odds of the posterior OR distribution falling within
the ROPE. Like other Bayes factors, BF
ROPE
allows for the
quantification of evidence for or against the interval null
hypothesis and can be interpreted in the same manner as BF
10
(with H
1
being that the true parameter value falls outside of
the ROPE). When BF
ROPE
provided substantial support in
favor of the parameter value falling within the ROPE, we
deemed the parameters “practically equivalent.”BF
ROPE
values were calculated using the R package bayestestR
(Makowski et al., 2019).
When comparing continuous variables between groups,
we utilized a Bayesian ttest similar to that proposed by
Kruschke (2013), albeit without data-dependent prior dis-
tributions. Dependent variables were standardized (M= 0,
SD = 1) and fit to an unequal-variances ttest model, with
a Normal (0, 1) prior on regression coefficients (i.e., the in-
tercept term and mean difference between groups), a Normal
(0, 1) prior on log-transformed standard deviation parameters
for each group, and a Gamma (2, 0.1) prior on ν,thedegrees
of freedom of the t-distribution. Model parameters were
estimated via Markov chain Monte Carlo (MCMC) as
implemented in the R package brms (Bürkner, 2017, 2018).
Posterior distributions of the parameters were based on
40,000 postwarmup MCMC draws from five separate
Markov chains. The primary parameter of interest was
the standardized mean difference between groups (i.e.,
Cohen’sd), which we summarized using the posterior me-
dian and 95% CrI. Group differences were deemed “sta-
tistically significant”when the full 95% CrI excluded zero.
Tests of the point null hypothesis were also supplemented
with a Bayes factor (BF
10
) calculated using the Savage–
Dickey Density Ratio (Dickey & Lientz, 1970; Wagenmakers
et al., 2010). In order to determine whether dvalues were
large enough to be practically meaningful, we further ex-
amined BF
ROPE
values to test the interval null hypothe-
sis that the population value of dlies within the interval
[−0.1, 0.1].
For ordinal variables, we fit an unequal-variances
ordered probit regression model (Bürkner & Vuorre, 2019;
Liddell & Kruschke, 2018) to the data, which assumes that
the ordinal dependent variable represents a normally dis-
tributed latent variable. In these models, the standard devi-
ation of the reference group (loudness hyperacusis) was
set to 1 in order to set the scale of the latent variable. The
other parameters estimated in the model were similar to
those in the Bayesian ttest (e.g., mean difference, standard
deviation for pain group, Cohen’sdeffect size), with the
addition of multiple intercept parameters needed to model
the category thresholds of the dependent variable. For these
models, we placed a Normal (0, 1) prior on the mean differ-
ence between groups, a Normal (0, 1) prior on the log-
transformed standard deviation, and a Student-t
3
(0, 2.5)
prior on each of the threshold values. Model parameters
were estimated in brms using the same MCMC procedure
described for the continuous models. Again, dwas the pri-
mary parameter of interest, and its value was tested against
the point null by examining whether 0 fell within the 95%
CrI (supplemented by BF
10
calculated using the Savage–
Dickey method). Furthermore, practical significance was
determined by examining BF
ROPE
values based on the in-
terval null hypothesis that the population value of dlies
within [−0.1, 0.1].
Results
Availability of Data and Material
Data from the current study are available from the
Coordination of Rare Diseases at Sanford (CoRDS) Regis-
try, organized by Sanford Research. Interested parties can
apply to access the data at https://research.sanfordhealth.
org/rare-disease-registry. Data generated by the authors
of this study from the original CoRDS data (e.g., binary
codes for qualitative responses) can be requested from the
corresponding author if written permission for the author
to share those data is obtained from Sanford Research.
Demographics, Background, and Onset
of Hyperacusis
The study sample was composed of 243 patients with
self-reported hyperacusis (152 pain hyperacusis, 91 loudness
hyperacusis per our operational definitions) between the
ages of 18 and 85 years (M±SD age = 45.65 ± 15.75 years;
49.8% female). The majority of participants were located
within the United States or Canada (n= 160 [66.9%]), and
95% of the sample identified as White. Most participants
(72.6%) had been formally diagnosed with hyperacusis
by a professional (audiologist: 26.9%, otolaryngologist:
33.5%, other physician: 10.1%, other medical professional:
2.2%). More detailed demographic information for the full
sample and loudness/pain subsamples can be found in
T2Table 2.
Comparing demographics between the two groups,
we found that patients with pain hyperacusis were on aver-
age 5.32 (95% CrI [1.16, 9.45]) years younger than patients
with loudness hyperacusis (d=−0.345 [−0.615, −0.073],
BF
10
=6.82,BF
ROPE
= 4.58). Despite the age difference
between patients with loudness and pain hyperacusis,
the two groups did not meaningfully differ in duration of
hyperacusis symptoms (d=−0.144 [−0.424, 0.122], BF
10
=
0.345, BF
ROPE
= 0.254). Sex ratio also differed between
the groups, with approximate parity in the pain hyperacu-
sis group and a predominance of women in the loudness
hyperacusis group (pain: 54.5% male, loudness: 36.8% male;
OR = 2.037 [1.193, 3.52], BF
10
= 5.07, BF
ROPE
= 2.97). Par-
ticipants in each group were similarly likely to be located in
the United States (pain: 64.0%, loudness: 61.8%; OR = 1.105
[0.639, 1.911], BF
10
=0.170,BF
ROPE
=0.095)andhadap-
proximately the same proportion of individuals with profes-
sionally diagnosed hyperacusis (pain: 73.0%, loudness: 72.0%;
OR =1.056[0.587,1.955],BF
10
=0.154,BF
ROPE
=0.104).
Williams et al.: Comparison of Loudness and Pain Hyperacusis 7
AJA-20-00209Williams (Author Proof )

Considering the laterality of hyperacusis, the majority
of patients in both groups experienced symptoms bilaterally
(pain: 83.9%, loudness: 78.9%; OR = 1.393 [0.723, 2.739],
BF
10
= 0.207, BF
ROPE
= 0.205). However, fewer patients in-
dicated that both ears were affected equally, with practically
equivalent proportions of individuals in each group endors-
ing asymmetric symptoms (pain: 48.0%, loudness: 51.6%;
OR = 0.865 [0.525, 1.487], BF
10
= 0.193, BF
ROPE
= 0.103).
Data were not reported regarding the laterality of asymmet-
ric symptoms, although monaural hyperacusis was reported
with approximately equal frequencies in either ear (right:
n= 21, left: n=22).Withregardtocommonhyperacusis
risk factors, the pain hyperacusis group reported signifi-
cantly increased rates of loud noise exposure (pain: 52.6%,
loudness: 39.3%; OR = 1.699 [1.022, 2.948]), although Bayes
factors were inconclusive regarding the practical significance
of this effect (BF
10
= 1.20, BF
ROPE
= 0.757). Conversely,
practically equivalent proportions of individuals in each
group reported a history of exposure to traumatic impulse
noise exposures such as blasts and gun fire (pain: 36.4%,
loudness: 31.1%; OR = 1.259 [0.743, 2.226], BF
10
= 0.221,
BF
ROPE
= 0.138) and serious head injuries (pain: 25.2%,
loudness: 20.5%; OR = 1.285 [0.681, 2.421], BF
10
= 0.196,
BF
ROPE
= 0.155). A diagnosis of hearing loss preceded the
hyperacusis diagnosis in approximately 20% of cases across
groups (pain: 20.3%, loudness: 21.6%; OR = 0.918 [0.484,
1.745], BF
10
=0.139,BF
ROPE
= 0.115), and a relatively
small proportion of individuals in each group reported
wearing hearing aids at the time of the survey (pain: 9.3%,
loudness: 7.2%; OR = 1.255 [0.460, 3.295], BF
10
= 0.108,
BF
ROPE
= 0.207). All but two participants reporting hear-
ing aid use (both in the pain group) indicated that they
wore hearing aids binaurally.
QoL and Functional Impairment
Confirmatory factor analysis of the five QoL items in-
dicated that they did not form a unidimensional composite
(CFI
cML
= 0.913, TLI
cML
= 0.826, RMSEA
cML
AQ4= 0.161;
Savalei, 2020). Thus, scores were compared between groups
on an item-by-item basis using ordered probit models.
Comparing QoL Item 1 (general self-perceived health)
between groups, patients with pain hyperacusis group re-
ported numerically lower scores than patients with loudness
hyperacusis, although scores were practically equivalent be-
tween groups (d=−0.132 [−0.415, 0.156], BF
10
= 0.317,
Table 2. Participant demographics and clinical characteristics by hyperacusis subtype.
Demographics and clinical characteristicsAQ3 n
Pain
/n
Loudness
Pain hyperacusis Loudness hyperacusis Full sample
Age (years) 150/89 43.69 (15.58) 48.96 (15.56) 45.65 (15.75)
Sex 145/87
Male 79 (54.5%) 32 (36.8%) 111 (47.8%)
Female 66 (45.5%) 55 (63.2%) 121 (52.2%)
Location 150/89
United States/Canada 102 (68.0%) 58 (65.2%) 160 (66.9%)
Europe 38 (25.3%) 26 (29.%) 64 (26.8%)
Australia/New Zealand 3 (2.0%) 4 (4.5%) 7 (2.9%)
Other 7 (4.7%) 1 (1.1%) 8 (3.3%)
Professional diagnosis 141/86 103 (73.0%) 62 (72.0%) 165 (72.7%)
Duration of hyperacusis 144/87
Less than 1 year 28 (19.4%) 15 (17.2%) 43 (18.6%)
1–3 years 35 (24.3%) 16 (18.4%) 51 (22.1%)
4–6 years 28 (19.4%) 13 (14.9%) 41 (17.7%)
7–10 years 16 (11.1%) 18 (20.7%) 34 (14.7%)
11–14 years 9 (6.2%) 7 (8.0%) 16 (6.9%)
15 years or more 28 (19.4%) 18 (19.4%) 46 (19.9%)
Symptom trajectory 147/87
Improved 11 (7.5%) 18 (20.7%) 29 (12.4%)
Same 20 (13.6%) 9 (13.6%) 29 (12.4%)
Worsened 75 (51.0%) 30 (34.5%) 105 (44.9%)
Fluctuated 41 (27.9%) 30 (34.5%) 71 (30.3%)
Symptom laterality 149/90
Bilateral 125 (83.9%) 71 (78.9%) 196 (82.0%)
Unilateral –left 11 (7.4%) 11 (12.2%) 22 (9.2%)
Unilateral –right 13 (8.7%) 8 (8.9%) 21 (8.8%)
Hearing loss 152/88 73 (48.0%) 42 (47.7%) 115 (47.9%)
Tinnitus 152/91 129 (84.9%) 79 (86.8%) 200 (85.6%)
Functional impairment (0–10)
Career 142/88 7.67 (2.89) 5.59 (3.40) 6.87 (3.25)
Domestic 147/89 7.15 (2.58) 5.75 (2.79) 6.62 (2.74)
Social 145/89 8.52 (1.82) 7.12 (2.73) 7.99 (2.31)
Note. Values for continuous variables (including 0–10 rating scales for impairment) are presented as mean (SD), while values for categorical/
ordinal variables are presented as n(%); n
Pain
/n
Loudness
= number of patients in pain/loudness hyperacusis group providing nonmissing response
to question.
8American Journal of Audiology •1–18
AJA-20-00209Williams (Author Proof )

BF
ROPE
= 0.231). Similarly, inconclusive results were ob-
served regarding QoL Item 2 (vigorous activity limitation;
d=−0.174 [−0.463, 0.114], BF
10
=0.420,BF
ROPE
=0.329).
Perhaps unsurprisingly, large group differences were ob-
served in QoL Item 3 (pain interference with enjoyment of
life), with the pain hyperacusis group reporting much lower
QoL due to pain interference (d=−1.104 [−1.440, −0.772],
BF
10
=6.25×10
5
,BF
ROPE
=4.37×10
5
). Numerically
lower scores in the pain group were also demonstrated on
QoL Item 4 (tiredness), although results were inconclusive
regarding whether a significant group difference was present
(d=−0.205 [−0.509, 0.097], BF
10
=0.553,BF
ROPE
=0.455).
On the final QoL item (depression), persons classified as hav-
ing pain hyperacusis again reported lower numerical scores,
but the ROPE Bayes factor indicated practical equivalence
between groups (d=−0.175 [−0.462, 0.118], BF
10
= 0.417,
BF
ROPE
= 0.329).
Three questions on the hyperacusis-specific survey
asked respondents to rate the impact of hyperacusis on
their occupational, domestic, and social functioning on an
11-point scale from 0 (no impact) to 10 (completely ruined
by hyperacusis). Comparing these measures between groups,
individuals with pain hyperacusis reported substantially
more impairment in the occupational domain (d= 0.701
[0.425, 0.987], BF
10
=2.94×10
3
,BF
ROPE
=1.93×10
3
),
as well as moderately more impairment in domestic function-
ing (d= 0.527 [0.261, 0.791], BF
10
= 377, BF
ROPE
= 161)
and social functioning (d= 0.541 [0.247, 0.840], BF
10
= 111,
BF
ROPE
= 70.1).
Symptoms Attributed to Hyperacusis
Pain in the “intermittent”category (e.g., “stabbing,”
“sharp”) was by far the most commonly endorsed in both
groups (pain: 63.8%, loudness: 29.3%), with individuals in
the pain hyperacusis group substantially more likely to en-
dorse this symptom (OR = 4.177 [2.328, 7.437], 4.82 ×10
4
,
BF
ROPE
=1.26×10
3
). Pain of the “continuous”type (e.g.,
“throbbing,”“dull ache”)waslessfrequentinbothgroups
(pain: 36.2%, loudness: 19.5%) and similarly more prevalent
in patients with pain hyperacusis (OR =2.272[1.219,4.409],
BF
10
= 5.07, BF
ROPE
= 3.84). However, this pattern was
not replicated for the category of “neuropathic-like”pain,
the prevalence of which was practically equivalent across
the groups (pain: 25.9%, loudness: 18.6%; OR =1.360
[0.661, 2.759], BF
10
=0.197BF
ROPE
=0.188).Although
the majority of individuals in both groups reported that
sound-induced pain occurred immediately after hearing the
sound, a sizable minority reported experiencing pain hours
to days after the inciting event (pain: 15.2%, loudness [ex-
cluding individuals who reported no pain]: 36.2%; OR =
0.321 [0.153, 0.682], BF
10
= 12.5, BF
ROPE
= 15.1). More-
over, the two groups differed minimally in the duration of
sound-induced pain (d=0.188[−0.151, 0.522], BF
10
=0.443,
BF
ROPE
= 0.362).
With regard to sound-evoked symptoms, a practically
equivalent proportion of participants in each group en-
dorsed scalp pressure, flu-like symptoms, fluttering/middle
ear myoclonus, hearing changes, sounds such as clicking
or popping, and paresthesia (all BF
10
< 0.33; see T3Table 3).
Individuals with pain hyperacusis were significantly
more likely to endorse facial pain (pain: 36.9%, loud-
ness: 23.5%; OR = 1.868 [1.027, 3.446], BF
10
=1.40,
BF
ROPE
= 1.04), ear fullness (pain: 66.2%, loudness:
51.7%; OR = 1.824 [1.070, 3.131], BF
10
= 1.79, BF
ROPE
=
1.18), and ear pressure (pain: 64.0%, loudness: 47.7%;
OR = 1.933 [1.151, 3.313], BF
10
= 3.26, BF
ROPE
= 1.95)
than those with loudness hyperacusis, although Bayes
factors were inconclusive regarding the practical signif-
icance of these differences. Numerically higher propor-
tions of pain hyperacusis patients also endorsed both
jaw pain (pain: 34.0%, loudness: 22.4%; OR = 1.760 [0.950,
3.246], BF
10
=0.875,BF
ROPE
= 0.671) and neck pain
(pain: 34.8%, loudness: 24.7%; OR = 1.601 [0.888, 2.952],
BF
10
= 0.542, BF
ROPE
= 0.420), with Bayes factors provid-
ing inconclusive evidence regarding group differences in
symptom endorsement.
Clinical Course and Symptom Fluctuations
The onset of hyperacusis symptoms was described as
sudden in 49.0% of the pain hyperacusis group and 49.4%
of the loudness hyperacusis group, with the difference be-
tween the groups being practically insignificant (OR = 0.982
[0.583, 1.689], BF
10
= 0.170, BF
ROPE
= 0.089). When de-
scribing the natural history of hyperacusis symptoms, par-
ticipants categorized their clinical course as Better, Worse,
Same, or Fluctuated. Examining the full 2 ×4 contingency
table (see Table 2), there was substantial evidence for a dif-
ference in symptom trajectories between groups (BF
10
=
3.86). Examining each category separately, the pain group
was substantially less likely to endorse symptoms getting
better over time (pain: 7.5%, loudness: 20.7%; OR = 0.320
[0.142, 0.697], BF
ROPE
= 11.7) and significantly more likely
to endorse symptoms worsening over time (pain: 51.0%,
loudness: 34.5%; OR = 1.96 [1.148, 3.392], BF
ROPE
= 2.22),
although the ROPE Bayes factor provided inconclusive evi-
dence that the latter difference was large enough to be of
practical significance. Notably, a similar proportion of indi-
viduals in each group indicated that their symptoms had
stayed the same over time (pain: 13.6%, loudness: 10.3%;
OR = 1.316 [0.581, 3.007], BF
ROPE
= 0.187) or fluctuated
between better and worse (pain: 27.9%, loudness: 34.5%;
OR = 0.734 [0.423, 1.306], BF
ROPE
= 0.189).
The majority of individuals in both groups reported
experiencing “setbacks”(defined as specific events that
noticeably worsened symptoms), with only 14.8% of the
loudness group and 13.0% of the pain group stating they
had never experienced temporary symptom exacerbations
(see F1Figure 1). Setbacks were most commonly attributed to
moderate or loud noise exposure, with equivalent proportions
of both groups identifying environmental noises as the cause
(pain: 77.1%, loudness: 70.8%; OR = 1.388 [0.729, 2.763],
BF
10
= 0.259, BF
ROPE
= 0.204). A minority of patients
attributed their setbacks to stress, exhaustion, or fatigue,
with inconclusive evidence for differences between groups
Williams et al.: Comparison of Loudness and Pain Hyperacusis 9
AJA-20-00209Williams (Author Proof )

Table 3. Sound-evoked symptom frequencies by hyperacusis subtype.
Symptom n
Pain
/n
Loudness
Pain hyperacusis Loudness hyperacusis OR (95% CrI) BF
10
BF
ROPE
Ear pain: intermittent 141/82 90 (63.8%) 24 (29.3%) 4.177 [2.328, 7.437] 4.82 ×10
4
1.26 ×10
4
Ear pain: continuous 141/82 51 (36.2%) 16 (19.5%) 2.272 [1.219, 4.409] 5.07 3.84
Ear pain: neuropathic-like 141/82 29 (20.6%) 13 (15.7%) 1.360 [0.661, 2.759] 0.197 0.188
Pain in face 141/85 52 (36.9%) 20 (23.5%) 1.868 [1.027, 3.446] 1.40 1.04
Pain in jaw 141/85 48 (31.6%) 19 (20.9%) 1.760 [0.950, 3.246] 0.875 0.671
Pain in neck 141/85 49 (34.8%) 21 (24.7%) 1.601 [0.888, 2.952] 0.542 0.420
Ear fullness 148/87 98 (66.2%) 45 (51.7%) 1.824 [1.07, 3.131] 1.79 1.18
Ear pressure 150/88 96 (64.0%) 42 (47.7%) 1.933 [1.151, 3.313] 3.26 1.95
Scalp pressure 141/85 45 (31.9%) 26 (30.6%) 1.056 [0.598, 1.902] 0.161 0.098
Flu-like symptoms 141/86 29 (20.6%) 13 (15.1%) 1.417 [0.689, 2.871] 0.218 0.212
Flutter/middle ear myoclonus 152/91 12 (7.9%) 4 (4.4%) 1.69 [0.608, 5.704] 0.136 0.330
Hearing changes/distortion 152/91 7 (4.6%) 7 (7.7%) 0.579 [0.202, 1.634] 0.130 0.364
Sounds (clicking, popping, etc.) 152/91 19 (12.5%) 14 (15.4%) 0.773 [0.374, 1.63] 0.140 0.175
Paresthesia 152/91 9 (5.9%) 4 (4.4%) 1.251 [0.427, 4.317] 0.083 0.236
Reactive tinnitus 122/77 99 (81.1%) 60 (77.9%) 1.217 [0.623, 2.498] 0.170 0.149
Headache exacerbation 122/71 79 (74.8%) 43 (60.6%) 1.204 [0.669, 2.221] 0.212 0.134
Vertigo exacerbation 91/57 46 (50.5%) 57 (40.4%) 1.509 [0.772, 2.917] 0.428 0.264
Note. Odds ratio (OR) and 95% credible interval (CrI) calculated using 15,000 samples from joint posterior distribution of category proportions.
Credible intervals that exclude OR = 1 are presented in bold. Bayes factor (BF) values greater than 3 (providing substantial evidence for a group
difference) are bolded, whereas BF values less than 1/3 (providing substantial evidence against a group difference) are italicized. n
Pain
/n
Loudness
=
number of patients in pain/loudness hyperacusis group providing codable/nonmissing responses; BF
10
= Bayes factor testing comparing
proportions between the two groups; BF
ROPE
= Bayes factor versus the interval null hypothesis log(OR)=[−0.1, 0.1], that is, the region of
practical equivalence to 0 (ROPE).
Figure 1. Comparison of setback frequency and severity between patients with loudness and pain hyperacusis. Percentages of individuals in
each group endorsing each response on the Coordination of Rare Diseases at Sanford survey regarding (A) setback frequency and (B) setback
severity. Ordered probit models were used to compare latent mean scores between groups, and the posterior distributions of latent mean scores
are depicted for (C) setback frequency and (B) setback severity. Vertical dotted lines indicate the grand mean score of the sample on each
variable.
10 American Journal of Audiology •1–18
AJA-20-00209Williams (Author Proof )

(pain: 11.0%, loudness: 19.4%; OR = 0.513 [0.232, 1.167],
BF
10
= 0.469, BF
ROPE
= 0.631). Notably, individuals in
the pain group reported that they experienced setbacks
significantly more often than individuals in the loudness
group (d= 0.617 [0.345, 0.897], BF
10
= 672, BF
ROPE
=
435). While 62.3% of individuals with pain hyperacusis
reported experiencing setbacks once per month or more,
only 32.1% of individuals in the loudness group reported
having setbacks this frequently (OR = 3.442 [1.939, 6.099],
BF
ROPE
=233).Amongthepatientswhoreportedexperienc-
ing setbacks, those with pain hyperacusis also reported greater
worsening of symptoms during setbacks than those with
loudness hyperacusis (d= 0.616 [0.282, 0.963]), BF
10
= 137,
BF
ROPE
= 98.9). However, there was inconclusive evidence
regarding whether the two groups differed in terms of the
amount of time needed to recover from a setback (d= 0.252
[−0.138, 0.668], BF
10
=0.613,BF
ROPE
=0.544),withthe
majority of patients (56.1%) reporting that these setbacks
typically last several days. Patients frequently perceived
the need to avoid loud noises during a setback, with the
majority of individuals in both groups responding affirma-
tively to the question, “Does the Participant’s recovery take
longer if they are exposed to a louder noise?”(pain: 91.5%,
loudness: 84.7%; OR = 1.922 [0.799, 4.803], BF
10
= 0.331,
BF
ROPE
= 0.517).
Comorbid Conditions
As expected, there was high comorbidity between
hyperacusis, tinnitus, and hearing loss in our sample, with
approximately 85% of patients in each group reporting tin-
nitus (pain: 84.9%, loudness: 86.8%; OR = 0.870 [0.410,
1.813], BF
10
= 0.125, BF
ROPE
=0.143)andnearlyhalfof
patients reporting some form of hearing loss (pain: 48.0%,
loudness: 47.7%; OR = 1.012 [0.607, 1.713], BF
10
= 0.166,
BF
ROPE
= 0.085). Of the patients who endorsed tinnitus,
the proportion whose tinnitus interfered with sleep was
substantially smaller and practically equivalent between
groups (pain: 39.0%, loudness: 50.0%; OR =0.728[0.43,
11.334], BF
10
= 0.327, BF
ROPE
= 0.195). A similar propor-
tion of individuals indicated that their tinnitus causes diffi-
culty concentrating while reading in a quiet room, with no
practically meaningful group differences in endorsement
(pain: 60.0%, loudness: 56.4%; OR = 1.166 [0.665, 2.086],
BF
10
= 0.200, BF
ROPE
= 0.113). The majority of patients
with comorbid tinnitus also noted that their tinnitus in-
creased in volume with exposure to sounds (pain: 81.1%,
loudness: 77.9%; OR = 1.217 [0.623, 2.498], BF
10
= 0.170,
BF
ROPE
= 0.149). Within the group of patients with reac-
tive tinnitus, there was no difference between patients with
loudness hyperacusis and pain hyperacusis in regard to the
duration of tinnitus increases after hearing a loud sound
(d= 0.130 [−0.180, 0.448], BF
10
= 0.312, BF
ROPE
= 0.229),
with the most common response (40%) being that tinnitus
exacerbations lasted several hours.
Headache disorders were also prevalent in our sample,
with equivalent proportions of individuals in each group
reporting both migraines (pain: 42.8%, loudness: 35.2%;
OR = 1.370 [0.810, 2.357], BF
10
= 0.316, BF
ROPE
= 0.197)
and tension headaches (pain: 54.6%, loudness: 48.4%;
OR = 1.280 [0.784, 2.203], BF
10
= 0.256, BF
ROPE
= 0.145).
However, chronic daily headaches of any type were experi-
enced significantly more frequently by patients with pain
hyperacusis (pain: 29.4%, loudness: 13.6%; OR = 2.534
[1.281, 5.149], BF
10
= 6.71, BF
ROPE
= 6.21). Headaches
occurred frequently in both groups of patients, with indi-
viduals in the pain hyperacusis group experiencing head-
aches slightly more often than individuals in the loudness
hyperacusis group (d= 0.361 [0.086, 0.627], BF
10
= 5.86,
BF
ROPE
= 4.17). Average headache severity, rated on a
1–10 scale, was also higher in the pain group as compared
to the loudness group (pain: M=6.19,loudness:M=5.20;
d= 0.466 [0.175, 0.758], BF
10
= 29.0, BF
ROPE
= 18.7).
The majority of patients in both groups who experienced
headaches also endorsed an increased frequency of head-
aches after being exposed to loud noises (pain: 64.8%,
loudness: 60.6%; OR = 1.204 [0.669, 2.221], BF
10
= 0.212,
BF
ROPE
= 0.134).
Additional comorbidities reported by over 5% of the
sample included TMJD, bruxism, osteoarthritis, phono-
phobia, anxiety disorders, depressive disorders, psychiatric
disorders in general, and functional somatic syndromes
(see F2Figure 2). Although not reaching the 5% threshold,
it is notable that 10 individuals (4.1%; eight in pain group,
two in loudness group) reported experiencing misophonia
comorbid with their hyperacusis. Phonophobia, including
both self-reported phonophobia diagnoses and descriptions
of pathological anxiety/panic responses evoked by sounds,
was present in just under 10% of the sample and endorsed
to an equivalent degree across groups (pain: 9.2%, loudness:
9.9%; OR = 0.911 [0.391, 2.195], BF
10
= 0.099, BF
ROPE
=
0.165). TMJD was reported by 20% of the sample, with
practically equivalent endorsement across groups (pain:
21.7%, loudness: 17.6%; OR = 1.271 [0.665, 2.498], BF
10
=
0.175, BF
ROPE
= 0.153). Bruxism was also relatively com-
mon, occurring in 35.8% of the sample and similarly across
groups (pain: 35.5%, loudness: 36.3%; OR = 0.965 [0.565,
1.667], BF
10
= 0.159, BF
ROPE
= 0.090). Anxiety disorders
(inclusive of phonophobia) were present in 21.8% of the
sample, with a significantly higher rate of endorsement in
the loudness group but inconclusive evidence for a practi-
cally significant difference (pain: 17.1%, loudness: 29.7%;
OR = 0.492 [0.262, 0.893], BF
10
=1.80,BF
ROPE
= 1.73).
Similar patterns were also observed for the categories of
depressive disorders (pain: 10.5%, loudness: 18.7%; OR =
0.515 [0.251, 1.071], BF
10
=0.553,BF
ROPE
=0.789)and
any psychiatric disorder (pain: 20.4%, loudness: 34.1%;
OR = 0.501 [0.281, 0.901], BF
10
=2.24,BF
ROPE
= 1.85),
although the group difference in depression prevalence
did not reach statistical significance (i.e., the 95% CrI
included OR = 1). Consistent with previous studies (Paulin
et al., 2016), we found a high prevalence of functional
somatic syndromes in individuals with hyperacusis, with
the pain hyperacusis group numerically more likely to
report one of these conditions (pain: 45.5%, loudness:
34.1%; OR = 1.597 [0.948, 2.749], BF
10
= 0.724, BF
ROPE
=
Williams et al.: Comparison of Loudness and Pain Hyperacusis 11
AJA-20-00209Williams (Author Proof )

0.465). Notably, when excluding chronic daily headache
from the functional somatic syndrome category, nearly
equal proportions of each group endorsed a functional so-
matic syndrome diagnosis (pain: 27.0%, loudness: 26.4%;
OR = 1.023 [0.571, 1.828], BF
10
= 0.146, BF
ROPE
= 0.098).
Comorbid Nonauditory Sensory Symptoms
The surveys also included several questions regarding
sensory symptoms in the vestibular, visual, olfactory, and
somatosensory modalities. Vertigo was a commonly reported
symptom, occurring daily or weekly in 27.8% of the sample
(pain: 29.2%, loudness: 25.6%; OR = 1.184 [0.653, 2.139],
BF
10
= 0.178, BF
ROPE
= 0.121). Among the patients report-
ing vertigo, neither the severity of vertigo symptoms (d=
0.058 [−0.273, 0.394], BF
10
= 0.260, BF
ROPE
= 0.176) nor
the frequency of vertigo attacks differed between loudness
and pain groups (d=−0.099 [−0.382, 0.192], BF
10
= 0.268,
BF
ROPE
= 0.181). Additionally, approximately half of pa-
tients experiencing vertigo reported an increase in vertigo
attack frequency or severity after exposure to loud noises
(pain: 50.5%, loudness: 40.4%; OR = 1.509 [0.772, 2.917],
BF
10
= 0.428, BF
ROPE
= 0.264). Discomfort due to bright
lights (i.e., photophobia) was also common, occurring daily
or weekly in approximately 40% of patients (pain: 39.7%,
loudness: 39.8%; OR = 0.994 [0.581, 1.756], BF
10
= 0.168,
BF
ROPE
= 0.093). Of the patients reporting photophobia,
no differences were found between loudness and pain groups
in terms of photophobia severity (d= 0.016 [−0.286, 0.322],
BF
10
= 0.217, BF
ROPE
= 0.135) or frequency (d=0.039
[−0.248, 0.328], BF
10
= 0.219, BF
ROPE
= 0.133). A sizable
proportion of individuals in each group also endorsed be-
ing bothered by strong smells (i.e., osmophobia; pain: 33.6%,
loudness: 38.3%; OR = 0.813 [0.463, 1.432], BF
10
= 0.213,
BF
ROPE
= 0.131) and being bothered by touch (pain: 22.4%,
loudness: 23.5%; OR = 0.929 [0.492, 1.747], BF
10
= 0.146,
BF
ROPE
= 0.111).
As an exploratory analysis, we also examined the
rates at which the various nonauditory sensory symptoms
co-occurred, additionally investigating the relationships
of these symptoms with psychiatric and functional somatic
syndrome diagnoses. Notably, disturbances in nonauditory
sensory modalities co-occurred at rates substantially higher
than chance. Of the individuals who reported daily or weekly
photophobia, 62.7% endorsed osmophobia (vs. 16% of those
without photophobia; OR = 8.475 [4.508, 16.472]), 35.4%
Figure 2. Comparison of comorbid conditions and nonauditory sensory complaints between patients with loudness and pain hyperacusis.
(A) Percentages of participants with loudness and pain hyperacusis who reported a certain diagnosis/symptom. (B) Posterior densities of each
odds ratio (OR) comparing respondents with pain hyperacusis to those with loudness hyperacusis. OR values are presented with their 95%
CrIs. Thick and thin horizontal lines indicate bounds of the 80% and 95% CrIs, respectively. The gray shaded area indicates the bounds of
the interval null hypothesis (i.e., the region of practical equivalence OR = [0.905, 1.105]). CrI = credible interval; TMJD = temporomandibular joint
disorder.
12 American Journal of Audiology •1–18
AJA-20-00209Williams (Author Proof )

endorsed tactile intolerance (vs. 16.3% of those without
photophobia; OR = 2.765 [1.496, 5.44]), and 43.7% en-
dorsed daily or weekly episodes of vertigo (vs. 16.4% of
those without photophobia; OR = 3.871 [2.127, 7.386]).
Similarly, individuals who endorsed osmophobia reported
higher rates of both bothersome tactile experiences (OR =
3.554 [1.884, 7.045]) and daily/weekly vertigo (OR = 3.425
[1.861, 6.501]), and individuals who endorsed tactile intol-
erance had higher rates of daily/weekly vertigo (OR = 4.274
[2.274, 8.561]). Exploratory analyses also revealed that
symptoms in nonauditory sensory modalities were associ-
ated with a functional somatic syndrome diagnosis (photo-
phobia: OR = 2.212 [1.288, 3.865]; tactile intolerance:
OR = 2.719 [1.300, 5.936]; vertigo: OR = 2.755 [1.542,
5.017]), with the exception of osmophobia, the prevalence
of which was equivalent between groups with and with-
out functional somatic syndrome diagnoses (OR =1.403
[0.801, 2.463], BF
10
= 0.327, BF
ROPE
= 0.213). Conversely,
the diagnosis of a psychiatric disorder was unrelated to daily/
weekly photophobia (OR = 1.128 [0.613, 2.072], BF
10
=
0.202, BF
ROPE
=0.118)ordaily/weeklyvertigo(OR =
1.207 [0.638, 2.285], BF
10
=0.196,BF
ROPE
= 0.139), al-
though osmophobia was more likely to occur in individuals
with psychiatric diagnoses (OR = 2.807 [1.537, 5.228],
BF
10
= 44.2, BF
ROPE
= 19.7). Patients with psychiatric
comorbidities were also numerically more likely to report
tactile intolerance, although evidence for this association
was inconclusive (OR = 1.896 [0.989, 3.617], BF
10
= 0.927,
BF
ROPE
= 0.873).
Perceived Response to Hyperacusis Treatments
Of our sample, over 50% of each group had attempted
to treat their hyperacusis with sound therapy, including both
self-directed protocols and those prescribed by professionals
(pain: 59.9%, loudness: 53.8%; OR = 1.273 [0.763, 2.173],
BF
10
= 0.248, BF
ROPE
= 0.141). The most common form
of sound therapy was self-administered pink noise (n= 85),
followed by self-administered white noise (n= 84), struc-
tured interventions that included counseling (n= 58), tinni-
tus retraining therapy (n=55),“Other”(n=48),hearing-aid
sound generators (n= 26), and the Neuromonics protocol
(n= 3). Participants reported engaging in sound therapy
for a median of 1–2 years, with the loudness hyperacusis
group reporting a moderately longer duration of sound ther-
apy compared to the pain hyperacusis group (d=−0.525
[−0.908, −0.137], BF
10
=8.42,BF
ROPE
=7.55).Notably,
the loudness group also reportedmoreperceivedbenefitfrom
sound therapy than the pain group (d=−0.425 [−0.806,
−0.047], BF
10
=3.12,BF
ROPE
= 2.84). Individuals in the
loudness group were substantially more likely to report
that sound therapy resulted in “significant improvement”or
“hyperacusis [being] almost eliminated”(pain: 4.4%, loud-
ness: 22.4%; OR = 0.176 [0.054, 0.557]). However, the pro-
portions of patients reporting (a) no change in symptoms
with sound therapy (pain: 38.5%, loudness: 32.7%; OR =
1.274 [0.618, 2.605], BF
ROPE
= 0.162) or (b) worsening
tinnitus/hyperacusis (pain: 27.5%, loudness: 18.4%; OR =
1.616 [0.702, 3.801], BF
ROPE
= 0.313) did not differ mean-
ingfully between the two groups.
The three medication classes reported as beneficial by
eight or more individuals were benzodiazepines (n= 30),
opioids (n= 9), and gabapentinoids (n= 10). Benzodiaze-
pines were reported as beneficial for hyperacusis symptoms
by equivalent proportions of patients in each group (pain:
11.8%, loudness: 13.2%; OR = 0.871 [0.400, 1.870], BF
10
=
0.115, BF
ROPE
= 0.150). In contrast, all individuals report-
ing symptom reduction from opioids or gabapentinoids
were in the pain hyperacusis group, likely due to the spe-
cific effects of these medications on nociceptive processes.
Discussion
Using a multinational patient registry, the current study
investigated how patients with loudness and pain hyperacusis
differed with respect to demographics, background/onset
characteristics, symptoms, comorbidities, and response to
treatment. On the whole, the two hyperacusis subgroups
were more alike than they were different, yielding equiva-
lent results on the majority of tested variables. However,
the group differences that were detected suggest that pain
hyperacusis is likely a more severe phenotype than loud-
ness hyperacusis, associated with more frequent and severe
setbacks, less improvement over time, a higher burden of
comorbid headache disorders, reduced benefit from sound
therapy, and more overall functional impairment. Notably,
the distinction between loudness and pain hyperacusis was
somewhat blurred in this cohort, as over 90% of patients
with pain hyperacusis perceived everyday sounds as unbear-
ably loud, and over 60% of our “loudness hyperacusis”
group experienced sound-induced pain at least monthly.
Thus, while our study does not indicate that pain and loud-
ness hyperacusis are pathophysiologically distinct condi-
tions, it does suggest that a pain-predominant phenotype
could serve as a prognostic marker within the hyperacusis
population.
Demographically, the loudness hyperacusis group
was slightly older and more likely to be female, but the
two groups were generally well matched on most other
background variables. However, reported symptom trajecto-
ries differed substantially between the two groups, with the
pain hyperacusis group more likely to report worsening over
time and less likely to report improvement. Individuals with
pain hyperacusis also reported higher scores on all three
functional impairment items when compared with the loud-
ness hyperacusis group. Group differences in QoL items
(other than the pain interference item) were small and
largely not significant, but the directions of these effects
were all consistent with slightly decreased QoL in pain
hyperacusis. Larger studies that implement more reliable
measures of health-related QoL may permit more precise
characterization of differences between these subsets of
the hyperacusis population.
Specific symptoms of hyperacusis were typically re-
ported to a similar degree between the two groups, although
several symptoms such as facial pain, ear pressure, and ear
Williams et al.: Comparison of Loudness and Pain Hyperacusis 13
AJA-20-00209Williams (Author Proof )

fullness were reported slightly more often by patients with
pain versus loudness hyperacusis. However, large group dif-
ferences were found in the domain of setbacks, with the pain
hyperacusis group reporting significantly more frequent and
severe symptom exacerbations than the loudness hyperacusis
group. As the majority of patients in our sample experi-
enced setbacks at least monthly, our study supports the
claims of patient advocates who argue that setbacks should
be considered a core feature of hyperacusis deserving of
additional clinical and research attention (Pollard, 2019).
Future research on this symptom cluster should consider
how to best quantify the frequency, severity, and duration
of setbacks, as such a measure would likely be extremely
useful when evaluating the safety and efficacy of clinical
interventions. Additional research is also necessary to char-
acterize the specific events that trigger setbacks, determine
whether setbacks are associated with measurable changes
in auditory physiology, and investigate the factors that en-
hance or inhibit recovery from setbacks, such as sound
exposure/avoidance and medication use.
Comorbidities were frequent in this sample of hyper-
acusis patients. As expected, tinnitus was the most frequently
reported condition, occurring in 85.6% of our sample (Anari
et al., 1999; Sheldrake et al., 2015). Approximately 80% of
individuals with tinnitus also reported that their tinnitus in-
creased in volume with sound exposure, consistent with previ-
ous reports (Schecklmann et al., 2014). Additional commonly
reported comorbidities included primary headache disorders,
psychiatric disorders, and functional somatic syndromes, all
of which have been associated with hyperacusis in prior stud-
ies (Cederroth et al., 2020; Goebel & Floezinger, 2008; Jüris
et al., 2013; Paulin et al., 2016; Schecklmann et al., 2014).
Most co-occurring conditions were equally prevalent in the
two groups, although individuals with pain hyperacusis
were more likely to report chronic daily headaches. Indi-
viduals with loudness hyperacusis were somewhat more
likely to report comorbid psychiatric disorders, particularly
anxiety disorders, although data were inconclusive regard-
ing the practical significance of this group difference. As
temporal trends in the onset of hyperacusis and these co-
morbid disorders were not assessed in the CoRDS survey,
we were unable to determine whether any of these conditions
could be considered risk markers for developing hyperacusis
(though see Goebel & Floezinger, 2008). Additional research
is necessary to better understand the ways in which comorbid
disorders confer hyperacusis risk and whether hyperacusis it-
self is a risk factor for developing certain comorbidities.
Individuals with both loudness and pain hyperacusis
further reported fairly high rates of nonauditory sensory
complaints, including photophobia, osmophobia, tactile
intolerance, and vertigo attacks, consistent with previous
qualitative findings (Ke et al., 2020). Though the severity
and frequency of nonauditory sensory complaints did not
differ between patients with loudness and pain hyperacusis,
the presence of one nonauditory sensory symptom was
highly predictive of additional symptoms in other modalities.
Moreover, the presence of a functional somatic syndrome
predicted symptoms of photophobia, tactile intolerance,
and vertigo, potentially indicating that these processes may
arise from the pathologic process of central sensitization
thought to underlie functional somatic syndromes (den Boer
et al., 2019; La Touche et al., 2018; Suhnan et al., 2017;
Yunus, 2015). With the exception of osmophobia, sensory
abnormalities were also not related to the presence of psy-
chiatric disorders, indicating that the occurrence and co-
occurrence of sensory symptoms cannot be easily attributed
to the presence of anxiety or trait negative affectivity. Fur-
ther research is warranted to better understand the overlap
between hyperacusis, other sensory complaints, and func-
tional somatic syndromes, and subsequent studies should
seek to determine whether central sensitization delineates a
clinically meaningful hyperacusis subgroup.
Lastly, we investigated relations between hyperacusis
subtypes and response to treatments, including sound ther-
apy and medications. The majority of patients in our sample
had utilized some form of sound therapy to treat hyperacu-
sis, although self-reported treatment outcomes were modest.
One notable finding was that individuals with loudness
hyperacusis were more likely to report substantial improve-
ment with sound therapy than individuals with pain hypera-
cusis, although approximately one third of pain hyperacusis
patients reported at least minor improvement. Additionally,
a substantial minority of patients (27.4% in the pain group,
18.4% in the loudness group) reported symptomatic worsen-
ing of either hyperacusis or tinnitus due to sound therapy,
indicating that these treatments may be harmful to a subset
of the population. The field of hyperacusis research would
benefit substantially from research designed to elucidate fac-
tors that predict differential response to sound therapy in
hyperacusis patients.
Few medications were reported by multiple patients
to be beneficial for symptoms, and only benzodiazepines,
opioids, and gabapentinoids were reported by at least 10% of
respondents. Gabapentinoids and opioids were both only
reported as beneficial in patients with pain hyperacusis,
indicating that certain medications targeting nociceptive
symptoms may be specifically useful for individuals with
pain hyperacusis but not loudness hyperacusis. Notably,
benzodiazepines were the medication class with the most
perceived benefit by patients across hyperacusis groups.
This finding is consistent with the hypothesis that hypera-
cusis is caused by decreased inhibition in the central audi-
tory system (Auerbach et al., 2014; Sheppard et al., 2020)
and indicates that benzodiazepines and other GABAergic
medications may reduce hyperacusis symptoms by counter-
acting maladaptive auditory gain within the central nervous
system. Benzodiazepines have also been found to be benefi-
cial in reducing tinnitus in some cases, although evidence
for this indication is mixed and may not be sufficient to
outweigh the potential harms of these medications (Jufas
& Wood, 2015). However, given the substantial disability
associated with cases of severe hyperacusis and the lack of
established pharmacological treatments, we believe that
additional research should further explore the potential ben-
efits of benzodiazepines in the context of controlled clinical
trials. Specific unanswered questions include (a) whether
14 American Journal of Audiology •1–18
AJA-20-00209Williams (Author Proof )

benzodiazepines provide long-term symptom reduction
with repeated dosing, (b) whether a short-term course of
benzodiazepines will improve recovery from a setback,
and (c) whether acute doses of benzodiazepines objectively
alter psychoacoustic correlates of hyperacusis such as loud-
ness discomfort levels and loudness growth functions. In
the absence of high-quality randomized controlled trials
supporting the use of benzodiazepines in this population,
we strongly caution against the routine prescribing of ben-
zodiazepines for patients with hyperacusis, although judi-
cious use of these medications (with frequent re-assessment
of benefits and harms) may be warranted in some cases.
Given the promising open-label results seen with safer medi-
cations such as nortriptyline and topiramate (Abouzari et al.,
2020), clinicians should consider prescribing benzodiazepines
only in cases that fail to respond to more conservative phar-
macotherapies and/or sound therapy.
Despite the rich information gleaned from this investi-
gation, our study is not without limitations. Most notably,
all information was self-reported by patients in the CoRDS
Registry and was unable to be empirically verified. More-
over, participants in this registry were self-selected and quite
possibly not representative of the broader hyperacusis popu-
lation. In particular, it may be the case that individuals
with pain hyperacusis were overrepresented in this sample, as
noise-induced pain is a particularly strong focus of Hypera-
cusis Research Ltd., the organization sponsoring the
CoRDS hyperacusis survey. Given that many individuals
in this registry were recruited from social media hyperacu-
sis support groups, it is also possible that individuals in
our sample differed from the population of hyperacusis
patients in terms of chronicity of symptoms, comorbid
conditions, illness severity, or sociodemographic factors
(Sautier et al., 2014). Another limitation concerns our
operationalization of pain hyperacusis. As no clinical or
research criteria have been established to parse hyperacu-
sis into loudness and pain subtypes, we chose the arbitrary
criterion of pain experienced daily based on (a) preliminary
results from this sample (Pollard, 2019) and (b) the notion
that pain caused by “everyday sounds”would result in
pain experienced at least daily. However, it may poten-
tially be the case that individuals who report no sound-
induced pain whatsoever differ systematically from those
who report sound-induced pain in any capacity, and addi-
tional research will be needed to determine whether such
subgroups provide additional prognostic information. A
third limitation is the lack of data in the CoRDS registry
on the perceived efficacy of cognitive-behavioral therapy
(CBT; Aazh et al., 2019), which has demonstrated some
efficacy in reducing hyperacusis symptoms and improving
loudness discomfort levels in a single randomized controlled
trial (Jüris et al., 2014). Future research investigating the
utility of CBT as a potential treatment for hyperacusis
should specifically investigate the degree to which response
to CBT may differ between individuals with and without
pain hyperacusis. Notably, as CBT has demonstrated effi-
cacy in treating other forms of chronic pain with diverse
etiologies (Hoffman et al., 2007; Morley et al., 1999; Pike
et al., 2016), the adaptation of existing CBT protocols to
pain hyperacusis remains a potentially fruitful area of fu-
ture research. Lastly, the information in the CoRDS Reg-
istry was gathered using an ad hoc survey measure rather
than previously validated questionnaires. As a result, it is
difficult to compare this sample of patients to other groups in
terms of hyperacusis or tinnitus severity, comorbid anxiety/
depression symptoms, QoL, and other constructs of inter-
est. Future survey studies in this population should addition-
ally include validated measures of sound tolerance symptoms
(Fackrell & Hoare, 2018; Greenberg & Carlos, 2018) and
other patient-reported outcomes (Cella et al., 2007). De-
spite the limitations of the CoRDS Registry as a source of
information on the phenotype of hyperacusis, we believe
that the information gathered from CoRDS and other pa-
tient surveys has the potential to identify important aspects
of the hyperacusis experience from the perspective of pa-
tients and to guide clinicians and researchers in providing
higher quality care to this particular patient population.
Author Contributions
Zachary J. Williams: Conceptualization (Lead), Data
curation (Lead), Formal analysis (Lead), Investigation (Lead),
Methodology (Lead), Visualization (Lead), Writing –original
draft (Lead), Writing –review & editing (Lead). Evan
Suzman: Conceptualization (Supporting), Methodology
(Supporting), Visualization (Supporting), Writing –original
draft (Supporting), Writing –review & editing (Equal).
Tiffany G. Woynaroski: Conceptualization (Supporting),
Formal analysis (Supporting), Resources (Lead), Supervi-
sion (Lead), Writing –review & editing (Equal).
Acknowledgments
This work was supported by National Institute on Deafness
and Other Communication Disorders Grant F30-DC019510
(awarded to Z. J. W.), National Institute of General Medical Sci-
ences Grant T32-GM007347 (awarded to Z. J. W.), and the Nancy
Lurie Marks family foundation (awarded to Z. J. W./T. G. W.). The
authors would like to acknowledge Hyperacusis Research, Ltd. and
Sanford Research for developing and maintaining the CoRDS hyper-
acusis registry, as well as Alyssa Mendel of Sanford Research for
assisting in data curation and management. The authors would
also like to thank Maura Black, David Treworgy, and other hyper-
acusis patient-advocates for their hard work in recruiting individ-
uals experiencing hyperacusis to register with CoRDS.
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