We are delighted to announce our interview with PhD. Paul Fuchs, Co-director, the Center for Sensory Biology at Johns Hopkins University. He is one of the most knowledgeable Hyperacusis Researcher in the world, with his research he could prove that there are nerve fibers in the auditory nerve which cause the hyperacusis pain.
He talks about what is hyperacusis, how it affects peoples lifes, the causes and why is hyperacusis research is a big challenge.
Here is the interview with Dr. Paul Fuchs, a professor at the Johns Hopkins University School of Medicine, whose laboratory has investigated trauma to the cochlear hair cells. The transcript has been lightly edited and condensed.
Q. Iāll start with a with a basic question. What is hyperacusis?
A. This word is unfortunate because itās not as specific as it should be for describing the disease state or the pathology. What it means, literally, is very sensitive hearing. That, as you know, is kind of inaccurate. Rather, one would like to have words which describe the set of conditions that people experience. Hyperacusis now more commonly means that people are disturbed or pained by loud sounds that previously were not painful. Hyperacusis as a clinical condition simply means that there is now an aversive or a painful experience when one hears sound.
Q. So do you think hyperacusis should have separate terms for people who perceive sound louder and for people that actually have pain from sound?
A. Yes. I think this is becoming clearer and clearer. There is probably a progression in hyperacusis from an initial condition when louder sounds become more irritating or annoying, to then becoming increasingly painful. But what will be helpful in the end is that we can define what the actual pathogenic mechanisms are and in so doing we can be clearer about what kinds of insults give rise to hyperacusis ā what sorts of actual damage or other sorts of mechanistic changes underlie the symptoms that people experience. I think weāre stuck with āhyperacusis.ā It is going to be a word that everybody will use, but at the end of the day, as we explore the biomedical mechanisms, weāll realize that one has to be more precise in the language.
Q. What is the main mechanism known to date of hyperacusis? Is it a psychological disorder? Is it an injury to the auditory pathway? What are your studies revealing?
A. The studies of a variety of laboratories are beginning to make progress on the notion that there is an underlying biological mechanism that begins in the periphery. I think itās a certainty that hyperacusis follows upon some kind of inner ear damage, and so this to me is a very firm indicator that hyperacusis is not simply psychological ā which is complicated in itself ā but rather is a consequence of peripheral inner ear damage. Whether there is one main mechanism, I donāt think that we can yet draw that conclusion. But what we can say is that, as we move forward, we are beginning to explore the kinds of changes that occur in the inner ear that may give rise to the conditions that then become hyperacusis.
Q. And is hyperacusis more a problem in the peripheral nervous system or is it something that happens in the internal structure of the ear ā in the cochlea or the hair cells? Where does the problem reside?
A. I like to draw the comparison between hyperacusis and tinnitus. They are consequences of peripheral damage in some way. But when one looks at tinnitus, it is pretty clear that there are a lot of central plasticity and central changes that conspire to provide tinnitus to people. Hyperacusis seems more strongly associated with a change in the peripheral sense organ itself, so hyperacusis is more likely to be something where we can localize the actual mechanism to the inner ear as opposed to the brain.
This is not to say that there arenāt also changes in central connectivity that help to explain hyperacusis. That almost certainly will be true, but I think in comparison to tinnitus, hyperacusis is something which Iām pretty confident reflects a change in the properties of the inner ear itself.
Q. Weāll start talking now about tinnitus. Many patients report that sound gives them pain or they perceive hyperacusis, but there is also a link with tinnitus. Many patients report more sound exposure gives them louder tinnitus, hyperacusis and pain. Can you comment?
A. So this is where you start to see the interplay between peripheral changes ā- the way the sense organ itself changes ā and the way the central nervous system follows that up with some forms of plasticity and more complicated kinds of changes. By comparison to pain in the skin or in the body generally, we know that there are changes in the sensitivity and excitability of the nerve fibers that innervate skin ā when you have a kind of painful nerve condition in the skin ā but there are also central changes where connections between neurons become stronger or weaker. And so tinnitus is probably more like phantom pain, which Iām sure you may have heard of ā that people who have lost a digit or a limb can report painful feelings in the missing limb.
So in conditions where the auditory periphery is no longer providing normal input, where you have some degree of hearing loss, then the brain begins to kind of self-generate activity as a replacement for the lost activity. This probably results from an imbalance in the input provided by what one would call the cognitive nerve fibers. In the somatic nervous system, for example, that means the fibers that tell us about touch and limb position, the cognitive inputs about our body ā vs pain fibers. We donāt really want to think about that pain. We just want to get away from it. So pain fibers initiate withdrawal symptoms.
And in the normal nervous system, there is a balance between input coming on pain fibers and input coming on the cognitive, touch, motion or other fibers. And thereās even a pretty well established principle that those cognitive nerve fibers inhibit the pain pathways.
So when we come to tinnitus, as we begin to lose inputs that are delivered by the cognitive nerve fibers that tell us about sound, then conceivably the Type II neurons which we have been studying, which we think may be analogous to pain fibers, begin to gain more or stronger access to parts of the nervous system which are going to mediate sensations of pain and the kinds of behaviors that mean withdrawal or aversion.
Q. So the hypothesis is that nerve cells are not signaling the sound in the normal wau and that is one of the causes of hyperacusis?
A. Almost certainly. Everything that weāve seen so far about these nerve fibers that look like pain fibers in the inner ear, is that they could become the basis for sensations that we now find as hyperacusis rather than normal hearing.
Q. Now maybe a tricky question but there are a lot of people that get hearing damage and hearing loss especially after rock concerts, and they donāt experience hyperacusis even with worse hearing loss than many hyperacusis patients. There must be problems of some other kind.
A. I agree, and that is a difficult question, so without knowing what the real biological mechanisms are, we canāt really say why one person may be different than another. But I think we can look at other examples of how people respond to varieties of insults and have different kinds of responses. We know that some people are very allergic to particular things and other people are not, so thatās a genetic difference in their immune systems that confer different sensitivities. We know that some people have very sensitive skin. Other people do not.
In the case of acoustic trauma and why there may be differences in the way that people respond to that ā with some developing the kind of pathologies and others not ā then we can at least talk about the fact that there may be differences in the patterns of damage in the cochlea.
The way that we measure hearing loss typically is a fairly crude instrument. We just ask āCan you hear this, can you hear that?ā But there may be much more subtle kinds of differences among people in the patterns of hearing loss. So we donāt know that the peripheral damage is the same in every case. There may also be differences in the genetics between people, so if it is the case that type II fibers are the pain fibers of the inner ear, they are not necessarily going to have the same pattern of gene expression in every person. They may be more or less subject to the kinds of changes that might give rise to hyperacusis and tinnitus.
And then we have to think about the fact that part of what happens in the ear are inflammatory responses ā the same kinds of tissue damage responses that are produced by histamine or other sorts of immune mediators ā and those are going to be different in different people. So one can imagine there to be a variety of ways in which the response differs, but until we know what the actual underlying biomedical process is, we canāt really address those differences.
Q. What is the state of hyperacusis research at the moment? What is the important focus and what studies should be done to study the mechanisms and to provide future hopes for treatment in the long term?
A. Weāve had a constant theme in our conversation, which is that until we understand the underlying mechanism, we canāt really begin to address ways of treating it. So from my view, I think weāve had a genuine breakthrough in the basic research in that weāve been able to confirm some elements of the idea that there really might be pain fibers in the cochlea, and that opens up a whole host of possibilities for exploring analogies between the way that people study pain in the rest of the body and what we might to do study pain in the ear.
Iāve been talking about these analogies as weāve gone along and the Type II afferents that our laboratory and others have studied, and we have now begun to gain real momentum for those as being potential pain fibers. We know something about the mechanisms by which they operate, we know how they are excited by chemicals, we know what their likely non-response to sound is and we know that they can be activated by tissue damage.
So now we can begin to look at: What are the molecules that mediate that response to tissue damage? Are they similar to the molecules that serve for skin pain? If so, can we use the same kinds of anesthetics to quiet down Type II afferents?
We donāt know that yet, but these are the sorts of leading hypotheses that one gains from this very important finding that there is a population of neurons in the cochlea which are almost certainly not there to respond to sound and they do respond to tissue damage. So I think weāre on the right track. The most important thing for us to do now is to determine how these potential pain fibers respond to tissue damage. Do they become hyperexcitable as pain fibers in skin do when you have a sunburn, for example? And where do they project in the brain? Where does that information go? Does it get to pain pathways?
To do these things and to begin to test them in the hyperacusis condition, we need to have an animal model so that we can ask: Does this animal have hyperacusis, does that hyperacusis depend upon Type II afferents, can we treat that animalās hyperacusis with drug XYZ, etc. We are on the way to doing that now. We are beginning to learn about the genetic specifications of the Type II afferent neurons, and that means we can manipulate those neurons genetically and so design experiments which are going to be much more informative about these questions.
Q. And this is exciting news and good news for people with hyperacusis ā that in the medium term or long term, might some kind of treatment appear?
A. Yes. Can I add another word about this? In the last year or so, weāve seen a significant increase in the interest of biomedical and pharmacology companies in these questions. So Iāve been very encouraged by the fact that, at the moment, for example, thereās three or four different contacts that Iāve received from the research and development people at big pharma and little pharma and biotech startups who are beginning to think about the commercial benefit of tackling these things. So I think thatās really encouraging and that will move things a lot faster.
Q. The main cause of hyperacusis?
A. The main cause is hearing loss, so thatās what we can say with any confidence ā beyond that, thatās as far as it goes.
Dr. Paul Fuchs, thanks so much for this interview
