Pain Hyperacusis in Relation to Acoustic Shock & Synapse Disconnection

Yes, I watched their presentation and wasn't convinced about it.

 

This article is also related to that topic:

A Case of Acoustic Shock with Post-trauma Trigeminal-Autonomic Activation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562182/

 

Another piece of the puzzle: this research is from a few years ago and was conducted at the University of Buffalo, they showed that following acoustic trauma, auditory nerve fiber degeneration in the cochlear nucleus in the brainstem led to upregulation of brain immune cells (microglia) thus potentially triggering inflammation. Another possible explanation for hyperacusis pain.

https://hearinghealthfoundation.org...in-inflammation-may-result-in-painful-hearing

 

Depends on where I am on the recovery scale, but at the moment I bouncing between mild discomfort and generally OK as long as everything is moderate, I can handle so much of it before it gets noticeable. It's the usual stuff though, drums, music with drum breaks in particular, kids screaming, yappy dogs, plates and cutlery etc.

A couple of obscure ones though that always get me no matter what are trolleys or anything on casters, especially the tall metal goods trolleys being pushed over rough ground, and cars driving in carparks that have painted floors.

How about you?

 

Interstesting that it suggests 2 types of damage, the frequency specific damage at the hair cells and then what seems to be a broader damage in the cochlear nuclei that continues to degenerate over many months that leads to a lower pain threshold due to the neuro inflammation. It could explain why at normal volume only certain frequencies hurt but at loud volumes, everything starts hurting no matter the frequency.

 

Yeah, it's rough.

For me, it's mostly high-frequency sounds. Stuff like microwave beeping etc or the phone ringing feels a bit grating but I don't tend to have trouble with fleeting sounds. The biggest trigger for me is 'artificial' audio sources especially from tinny laptop speakers or phone speakers. Stereo systems that are better quality feel easier on my ears but yeah something about that cheap tinny sound absolutely kills my ears - it has a very 'sharp' and scratchy quality to it. I also find that this sort of audio tends to produce a sort of wind-up reaction in my ears where it will trigger reactive tinnitus and hyperacusis and it also triggers facial numbness which is kind of bizarre but I guess that's hyperacusis for you.

Hoping we will both make full (well, as close to normal as possible) recoveries!

 

I came across this and thought it relevant to post here. An account of a woman who suffered sudden hearing loss in one ear resulting in debilitating tinnitus and hyperacusis - it was so bad she couldn't listen to music as the tinnitus distorted everything and the hyperacusis was equally disabling. She ended up opting for a cochlear implant in the affected ear. The result was that: "My hyperacusis, although it has not completely disappeared, has drastically improved and the tinnitus has become almost unnoticeable when I have my audio processor on. Paradoxical though it may be, I can finally enjoy silence again!"

https://blog.medel.com/cochlear-implants-for-tinnitus-hyperacusis/

I'm unsure whether it was more a case of pain or loudness but it seemed pretty bad in any case. Anyway, to get to the point this kind of brings me hope because if restoration via a cochlear implant, which is a pretty poor imitation of normal hearing, can alleviate tinnitus and hyperacusis to this degree then I feel optimistic that regenerative medicine could yield similar results.

 

I really needed some good news like this. I hope when FX-322 restores the OHCs, IHCs and synapses where there was a loss of hair cells should it reduces hyperacusis or completely gets rid of it.

 

Nice find. I wondered sometimes about cochlear implants as well, I've done little to no reading on them so really know not much about them. From what I have read though, it sounds like they can be very destructive to whats left of the inner ear as they get inserted. Makes me think if could be the case that the implant destroys or wipes out the semi-damaged components that are causing problems such as tinnitus or hyperacusis as they are being inserted.

 

I’m really desperate for a regenerative cure to hyperacusis and tinnitus. I went from wanting to be a musician to not being able to listen to music without painful whistling. I’m really banking on FX-322 in the next 3-4 years, I just want a second chance at life I’m only 16. Hopefully I can live my dreams out with the help of modern medicine

 

I don't mean to bring you down, just to be realistic... there have been rumours about repairing hearing, the "pill that cures hearing loss", supplements etc for like 30 years, and all of them got nowhere...

Remember Theranos? There are a lot of companies that promise some sort of revolution regarding health issues, blood testing etc etc... Theranos wanted to "change the world" and in the end it was just a scam, and investors lost like 1bn dollars on that.

 

Have you read about Theranos?? Frequency has proven their drug worls conclusively. Fx-322 is not a scam - sure, we don't know exactly how effective it will be and what the outcome of the trials will be but I really don't think you can compare it to Theranos. Also how could the participants in the Phase 1/2 trial have shown improved hearing then? You can't placebo your way to better hearing.

Also it was only discovered that birds could even regenerate hearing in the late 1980s - prior to that, the possibility of hearing regeneration was basically unknown. So I don't think you're totally accurate in saying there have been promises to restore hearing for 30 years...
Significant progress has been made. And don't compare supplements to the current regenerative drugs in the pipeline.

 

Sorry, I’m still cautiously optimistic

 

Completely agree with you - comparisons to Theranos are kind of lazy and disingenuous imo. There were so many red flags there - very high staff turnover, workplace bullying, failed quality control plus Elizabeth Holmes' inability to coherently answer questions in interviews.

 

Same, but more so for something like XEN-1101 than FX-322. (I'd happily try FX-322 if it happens though).

 

Well, I would love to be wrong and look back let's say 5 years from now and see that the possibility to regenerate hearing exists. We'll see.

 

When it comes to potential treatments for hyperacusis in particular, I'm also skeptical because hyperacusis never seems to get a mention in current trials for either being a candidate for testing in future trials or, potential off label use. But for anything else hearing related including hearing loss, tinnitus or a combination of the 2 (without hyperacusis) then I am far less skeptical and I think there is much more hope for these sufferers due to what is currently in research and the fact that tinnitus in particular is being looked into, either in terms of further trials or, off label use for what are primarily hearing loss drugs.

I have a lot of hope for FX-322, Otonomy, Hough etc. for purely hearing loss and/or tinnitus sufferers, but am reserved when it comes to hyperacusis. I don't consider myself a tinnitus sufferer even though I've had it for most of my life. I would call myself a severe hyperacusis sufferer with tinnitus. Tinnitus never bothered me, it would never have stopped me playing music or going out, it would never have made me seek out ENT's/audiologists or made me join this forum. But the second I got hyperacusis through acoustic shock my life changed. I didn't even consider a link between tinnitus & hyperacusis at first. It took me over a year of consultations telling ENTs about my hperacusis to realize, holy shit I have tinnitus as well maybe I should be mentioning it. I checked out this site years ago but didn't join because I didn't think it applied to me because I was so preoccupied with the notion that hyperacusis was my condition and not tinnitus. So over the years I read a bit of this site and realized a lot of other tinnitus sufferers also had hyperacusis, and so I finally joined. Tinnitus doesn't bother me nearly as much as hyperacusis, and if anything my tinnitus is enabling me to use this site to discuss my hyperacusis. The only thing I'm grateful for is that my tinnitus is more of an annoyance to me as opposed to what some on here seem to suffer, in that they suffer from tinnitus in the same way I suffer from hyperacusis (debilitating).

So many questions about it in my head. Is hyperacusis, an extreme/chronic form of tinnitus? Or, Is hyperacusis a completely separate injury in its own right? If it is the former then I have a lot of hope for FX-322 etc. but if it is the latter then not so much. Maybe a combo of FX-322 and XEN-1101.

My tinnitus and hyperacusis usually go hand in hand, when ones bad the other is too, and so another question I have is what potentially triggers what? If a tinnitus spike triggers my hyperacusis then I have hope for FX-322. But if a hyperacusis spike/setback triggers my tinnitus, I have more hope for something like XEN-1101.

Hyperacusis is not like an on/off switch for me. Its more like a dimmer switch that gets better when I avoid noise and then gets aggravated and inflamed when I have too much noise exposure. So with that in mind I don't see how it could be a dead hair cell or disconnected synapse (off switch). I feel its more likely something different. I keep thinking with the amount of damaged hair cells there must be in this world why isn't there more hyperacusis going around. Coupled with the fact the my hyperacusis started directly after acoustic shock, I remain convinced something else is fundamentally damaged, and it was the acoustic shock that caused that damage.

Hyperacusis, from absolutely everything I've read about it is the thing that leaves everyone scratching their head and at a loss as to what could potentially cure it. Hearing loss has potential to be fixed, tinnitus has potential, synapse disconnection has potential, and these conditions all point more to inner ear pathologies. The most plausible things I've read on hyperacusis (some since I started this thread) seem to indicate something not necessarily located in the inner ear, but potentially closer to the brain, or at least somewhere along the nerve pathway to the brain. (Acoustic trauma symptoms cluster, particularly the hypoxia nerve damage, and so if its nerve damage that causes hyperacusis, I'm looking out more for a nerve regeneration drug or at least a nerve pain blocking drug).

Whatever happens I can't wait for the first real discovery of any drug that does something genuinely measurable for any hearing condition because it will at least if nothing else start the process of elimination. If and when say (a successfully released) FX-322 gets used on and off label for various hearing conditions, it won't take long to establish which conditions it fixes and which it does nothing for. Same with Otonomy, and again same with Hough. If it ever turns out that people with only hearing loss and/or tinnitus are being cured with these inner ear drugs, but people with hearing loss and/or tinnitus AND hyperacusis are recovering from everything expect their hyperacusis, then it will eliminate a whole load of potential wasted effort on inner ear hyperacusis research and enable it to be focused elsewhere.

 

I am skeptical because all ENTs I have checked with over the years, and these have been a lot, and very experienced, said it is almost impossible to regenerate hearing. Some of them discussed what was thought years back, and how things evolved, and what was the state of the art now, and they were very skeptical about the possibility to regenerate lost hearing, as everything in the hearing system is tiny and too complex, and has to be connected exactly in the right way. The right hair cell would have to be connected to the right synapse etc... it is like a tiny construction set where every piece has to be connected to the other right piece, it is just not a matter of regenerating anything, but the whole system has to reconnect as it was before.

And one of my doubts about this also lies in the fact that once hair cells are bent, deteriorated or dead... maybe the connections are lost for good too. I mean, if one loses hearing at let's say high frequencies and that stays for years, probably the connections and synapses to the higher parts of the hearing system (neurons, nerve, brain) are just lost for good, as they have had no function for years and years.

 

Yes @Juan I agree with everything you say about hearing regeneration, I'm probably not quite as skeptical as you based on what's known about FX-322, and I think people with solely hearing loss and/or tinnitus do have a lot to be hopeful for, but still, for such an intricate thing to be successfully rebuilt will be almost unbelievable.

I'd love it if something could fix hair cells and synapses but remember though that this thread is coming from the sole point of view of what possibly causes pain hyperacusis in particular, whether or not deafness or tinnitus are present. Again I am no expert but from the deductions I come to, pain hyperacusis is a fundamentally different thing to hearing loss and tinnitus. I still lean to the theory that the pain is caused by nerve damage that gets very rapidly inflamed and then takes a long time to calm down, as per the nature of pain hyperacusis. And in turn a nerve damage pain management drug might not only stand a better chance of getting successfully developed than, as you rightly say something that could build back the infinite intricacies of the inner ear, but it might be the only option anyway (except for a nerve regeneration drug if such a thing exists). I'm on your side, I'm just trying to envisage / deduce as best I can the possibility that pain h could well be such a separate problem from hearing loss and tinnitus that it doesn't even bring inner ear regenerative meds into the equation anyway.

And even if, say pain hyperacusis is down to hair cells and synapses (which again I doubt because there would surely be so many more cases of it), I still think a nerve pain management drug would stand a better chance of development than a inner ear regenerative drug, as cautiously hopeful as I am for FX-322 etc.

At the end of the day, if I had to take 10 different types of nerve pain drugs a day for life (that were proven to be effective) to keep hyperacusis pain under control, I'd happily do it.

 

After a long time with hearing problems I have had a varied set of symptoms, and it is sometimes hard to tell whether the pain is located at a particular point or whether it is just pain that irradiates from somewhere else...

Also hearing perception is tricky, for some people like me it fluctuates, goes a bit up and down, with a long term downline trend (this is, progressing towards hearing loss).

My eyes get kind of tired due to spending a lot of time at home or the office... Sometimes my tired eyes seem to somehow interact with pressure irradiating from my ears. I wonder if this has something to do with nerves running close to each other...

 

@100Hz, replying to you here rather than the FX-322 thread as I feel we are getting slightly off-topic!

I think the question of why some people get pain and others don't is an interesting one even if they both have OHC damage. I like Paul Fuchs' answer to this - that it could possibly be dependent on, say, gene expression in the Type 2s so that not every person is going to have the same response to damage. I guess it's similar to how other conditions can produce a wide range of symptoms but not everyone is going to exhibit the same symptoms even if they both have the same underlying disease. Perhaps we just got the shitty end of the genetic stick with this one. E.g. on page 10 of the summary from the 2017 Hyperacusis Research conference at the ARO researchers found that people who develop tinnitus and hyperacusis experience a dysfunctional level of central adaptation.

https://hyperacusisresearch.org/wp-content/uploads/2017/03/ARO-2017-Technical-Summary.pdf

So perhaps it's more the way our systems adapt (or fail to) to the damage that leads to symptoms like tinnitus and hyperacusis?

Page 8 of this upload also discusses whether people who develop hyperacusis are more vulnerable to this kind of damage, e.g. by being less able to produce heat shock proteins (HSPs) under stress which are protective. So perhaps we have some kind of in-built vulnerabilities in our systems?

These insights are really thought-provoking and I am still trying to digest everything. The 2016 ARO symposium summary was also focused on pain hyperacusis and I read through the summary of it to see if there any discussions on the role of the middle-ear. The findings seem to point more to inner ear pathology, e.g.:

https://hyperacusisresearch.org/an-md-summary-of-the-2016-aro-hyperacusis-symposium/

"The biology of hyperacusis pain isn’t primarily due to stimulation of fibers in the 5th, 7th, 9th and 10th cranial nerves. These nerves serve parts of the eardrum (tympanic membrane), middle ear, and opening of the Eustachian tube in the throat, so some hypothesize that they mediate the experience of hyperacusis pain as well. Yet for the most part this doesn’t explain why ‘normal’-intensity causes pain.

So if we're talking about what triggers it again and again, and at lower sound intensities it seems to be suggesting that this must be mediated more by the inner ear?

Also, Ulf Baumgaertner's presentation again brings up middle ear pathology but it seems there's not much conclusive evidence for it as afferents of the trigeminal nerve are not excited by sound frequency. He also states that it is unlikely that the TTM and the stapedius could be causing hyperacusis pain as TTM spasm results in pulsing tinnitus and since the stapedius contracts during speech, we would feel pain when talking. But some people report TMJ-like pain so the muscles controlling the jaw and TMJ could also be playing a role here.

Also, an audience member pointed out that there are projections from the trigeminal ganglion to the cochlea and into blood vessels so autonomic participation of the trigeminal nerve could also play a role. That seems significant though as, in theory, that could suggest that the diverse facial/trigeminal symptoms that people experience could actually be coming from the cochlea.

The presentation on neuropathic pain also states that when nociceptors inhabit a chronically inflamed environment it leads to sensitisation hence why we could be experiencing setbacks at a much lower level than normal?

I feel like I'm playing devil's advocate slightly here - it's all so disorienting. The acoustic shock paper you linked puts forth a very comprehensive hypothesis but then the above findings very much seem to rule out middle ear pathology so I'm honestly not sure. The fact that Myriam Westcott had a patient who responded to a nerve blocker though is intriguing though and sort of makes me question that. I personally suspect that it would be more unusual to have middle ear pathology on its own with no inner ear pathology at all. The part that makes me think it may be OHC damage is why do some frequencies hurt but not others even if they are at the same volume level? To me, that would suggest that there is some structural damage in the cochlea at certain frequencies but I'm not sure. It's a shame that the 2020 conference couldn't go ahead as there would have been a presentation on the middle ear and TTM.

 

Thanks @serendipity1996 will go through it all in the next couple of days.

 

Okay... so you guys are saying that even if hair cell and synaptic treatments are successful at regenerating the respective functions, it wouldn’t do anything for H? I wanna cry...

 

I wouldn't worry too much about it yet. The one thing I'm convinced about is that there's a fundamentally damaged something, somewhere which is why setbacks happen and cause renewed inflammation and pain no matter how well we seem to recover. Either cochlea OHC damage, or mid ear physical damage, or an altered nervous system. Or a combination of 2 or 3 of them keep getting aggravated over and over.

After everything I've read I'd say there's a big chance that the cochlea is responsible for being the initiator although I lean slightly towards it being mid ear. But there's a lot of arguments for both sides and is far from conclusive.

It gets much more muddy when you try to consider what is triggering what though. And even more muddy when you split it further and try and think about what triggers the first acoustic shock, and then what triggers follow up acoustic shocks or setbacks.

I think whatever happens fx322 will do something for acoustic shock noxacusis. If not a full cure, a partial one, and if it fails to do anything for the facial noxacusis part of our condition and setbacks etc. at all then it will firmly put the spotlight on the mid ear and / or nervous system.

 

I do think we will uncover a lot more about hyperacusis in the next 5 years or so. Even if FX-322 is less effective for us, it's still progress as it means we can potentially 'rule out' some causes and focus more on others (e.g. the middle-ear).

Research into hyperacusis seems to be progressing exponentially - I mean, 10 years ago it merited perhaps a few obscure references in the literature - there was no advocacy group (Hyperacusis Research was founded in 2011). I think the discovery of the Type 2 neurons, in particular, has been a big milestone.

Paul Fuchs and his team at Johns Hopkins are still studying mice models but I would assume their ultimate aim is to get a drug into clinical trials, at least that's the impression I got from emailing him about his work.

We also have Sound Pharmaceutical with a drug that combats inflammation in Phase 3 which could be helpful if hyperacusis is maintained by a chronically inflamed cochlea.

 

I haven't had much interest in Sound Pharma since that drug is for menieres but this info has has piqued my interest. This may be a stupid question but is there any chance it would also help with potential inflammation in the middle ear?

 

I'm not actually sure - I assume it's more targeted towards the inner ear but it could also help combat middle-ear inflammation.

 

There is no evidence that hair cell regeneration will correct pain hyperacusis. Yet people continue to support this idea.

 

To be honest I think it's more that we know very little about pain hyperacusis in general so we can only make educated guesses. But what about the fact that researchers at the 2017 ARO Hyperacusis Research meeting said they believe hair-cell regeneration could potentially improve pain hyperacusis? Nobody's saying anything with certainty but I think it's okay to express hope that it might. What do you believe would correct it?

https://hyperacusisresearch.org/wp-content/uploads/2017/03/ARO-2017-Technical-Summary.pdf (see pages. 7-8)

 

I've had a good read of all that @serendipity1996, thanks, very interesting and it goes into a lot of detail on cochlear pathology. I can see where you're coming from and think you're absolutely correct, it would be wrong to assume that it is all down to the mid ear only, mainly due to the frequency specific sensitivity and pain side of noxacusis which now suggests cochlea damage to me as well.

I don't know if you've noticed this too, but what I find so strange now after reading about it from both angles (cochlea vs. mid ear) is that neither research is particularly acknowledging of the other, there's a glaring lack of joined up thinking. Most of what I read about cochlea Type II sensitization does not seem to address the possible relationship with acoustic shock mid ear damage (even seems to dismiss it yet repeatedly refer to aching facial pain), and the only reference to Type II sensitization in the acoustic shock paper is that mid ear inflammation can diffuse through the round window and possibly cause Type II sensitization that way. There's no direct mention that it is also caused directly by noxious noise (that could well be responsible for the acoustic shock). But I'm starting to really see a connection between the 2 of them on how they may possibly trigger and interrelate with each other.

I would like to one day see a universal acknowledgment as well that there are evidently 2 main specific types of pain related to noxacusis and each one appears to be the result of a very different pathology. To simply say 'noxacusis or pain hyperacusis' I think is too broad now and to actually separate the pain types helps to understand the different possible underlying pathology in more detail. The models and hypotheses for example on central gain etc., how the cochlea nociceptors are communicating with the brain etc., and how the parts of the CNS are adjusting to pain / noise signals etc. seems to be related strictly to the cochlea and is directly related to the actual response to noise by the cochlea, i.e. the instant sharp specific frequency pain / sensitivity. But the delayed facial pain and even modulated tinnitus would suggest a secondary pain/symptom, and something completely different such as the theory on mid ear inflammation and TGN sensitization as a result of physical acoustic shock.

'Allan applied his expert knowledge of neuropathic pain to pain in hyperacusis. Based on hyperacusics’ descriptions of their pain—burning, stabbing.' Notice the way that 'burning and stabbing' are grouped together. I think this is too broad. When you for example setback hearing a dog bark as a noxacusis sufferer it is instantly too loud and sensitive but doesn't last (at first), I think this is where the 'stabbing' occurs, whether it is in the cochlea itself or more likely triggered in the mid ear by the cochlea response, the very instance of the sound, is what's causing this stabbing. The burning aching however is typically delayed, long lasting and facial and in my view is the result of secondary mid ear inflammation. I just see 2 very different types of pain and pathology regularly being bundled together as one.

You mention, 'Also, Ulf Baumgaertner's presentation again brings up middle ear pathology but it seems there's not much conclusive evidence for it as afferents of the trigeminal nerve are not excited by sound frequency'. The trouble with this statement is that it is suggesting that sound could be triggering facial neuralgia directly which doesn't make much sense in itself. It doesn't take into account the full chain of events of sound triggering an acoustic shock that then leads to the mid ear inflammation and TGN sensitization which could then easily explain facial neuralgia. Ongoing non-noxious sound then continues to excite and further inflame an already inflamed mid ear and a damaged TTN that cannot rest and recover (this could explain why people still suffer facial pain in particular from even non-noxious noise. Of course a highly inflamed cochlea could also possibly react to non-noxious noise, I don't know, but I doubt it would cause this kind of facial pain directly, especially in silence where perhaps the mid ear still might do. Also would the stabbing sensation not be ongoing?). In addition, ongoing non-noxious noise also continues to possibly stimulate nociceptors in the cochlear where although the sound may be non-noxious in volume, the specific frequency is noxious (I completely agree with you on this part now, I also think it could be one of the best explanations for a trigger for acoustic shock and setbacks as well. In essence this could be THE permanent damage that I believe repeatedly keeps causing setbacks no matter how well we recover and FX-322 would in theory be great for it). If it is all initiated by the cochlea however (the acoustic shock, the frequency specific pain, and the delayed facial pain) then its also a very positive sign for FX-322 and maybe SPI-1005.

This one also, 'He also states that it is unlikely that the TTM and the stapedius could be causing hyperacusis pain as TTM spasm results in pulsing tinnitus and since the stapedius contracts during speech, we would feel pain when talking. But some people report TMJ-like pain so the muscles controlling the jaw and TMJ could also be playing a role here.' This seems to be trying to hypothesize that a healthy, normally functioning middle ear is generating facial pain and not taking into account that it's not the movement of these muscles and nerves that cause the pain but the fact they've been sensitized and inflamed as a result of the acoustic shock secondary to the cochlear damage / Type II sensitization. In a case where there was only cochlea damage, indeed causing its own type of pain, I'd guess these symptoms are more likely to be only instantaneous frequency specific sensitivity and pain with no delayed facial pain anyway (TGN not yet sensitized plus no middle ear inflammation). It's this kind of thing that makes me think the types of pain really need separating now for research to become more detailed.

In short I'd say that the lingering facial pain is more likely down to any stimulation of the damaged mid ear, even non-noxious noise (this could explain why silence is sometimes all that will help. Also it could explain why it only gets worse if you try and 'push through the pain'). Even non-noise stimulation may still excite the middle ear (this could explain why sometimes even silence doesn't help). Setbacks however I think are more likely to be the result of repeat stimulation of sensitized Type II afferents because from my own experience and from what I read of a lot of others, setbacks usually follow noxious or frequency noxious noise exposure that causes the initial pin prick sensations in the ear (the stabbing?), and again whether this stabbing actually occurs inside the cochlea or is more likely the mid ears response to the cochlea nociceptor stimulation, this does appear to be as a direct instant reaction to actual noise (as opposed to a delayed secondary inflammatory pain). This bodes really well for fx322 as long as the mid ear pathology hasn't become a self sustaining problem in its own right.

With regard to the projections from the trigeminal ganglion to the cochlea, this is interesting because it puts a direct link between the two and it could in theory turn all the above upside down as well. I've read about this before and I'm open minded about it although I'm still slightly more steered to the possibility that this is a one way inflammation street into the cochlea that is responsible for symptoms such as tinnitus modulation etc. (tinnitus fluctuating with facial pain). For this theory to be the sole cause of the facial pain would seem to rule out a lot of the acoustic shock symptoms cluster theory. I think the acoustic shock theory is more likely and conclusive though given that extensive paper on it. Of course however, if the single lingering action of the acoustic shock was to simply sensitize the TGN (but not stimulate it from within the mid ear, again doubtful due to apparent mid ear inflammation), then who knows, maybe cochlea inflammation could then affect the whole TGN via the cochlea TGN nerve endings. Another possible win for FX-322 and SPI-1005 if this is the case anyway.

The main thing that I'm still having trouble with in regards to the Type II sensitization causing noxacusis, is again how few noxacusis sufferers there appear to be in relation to the surely larger amount of people who must have OHC damage but simply just go deaf without pain. I'm starting to buy into the possibility it's down to genetics / predisposition based on this because so much else seems to be stacking up in favour of this theory for it to be ignored.

I've been working on some models based on the more feasible possible relationships between these 2 different angles, I'll post them soon once they're finished.