Pain Hyperacusis in Relation to Acoustic Shock & Synapse Disconnection

[serendipity1996]

@100Hz

Great post and I fully agree with many of the points you're making especially the middle/inner ear dichotomy - will need a few days to compose a proper reply!

 

[Croaker]

Why is it so hard to calm whatever is going on in the middle ear, if it really is playing such a major role? It isn't isolated like the cochlea.

 

[Orions Pain]

Why is it so hard to calm whatever is going on in the middle ear, if it really is playing such a major role? It isn't isolated like the cochlea.

I'd say lack of an easy/non-invasive way to actually see into the middle ear. In order to calm it they'd need to know what needs to be calmed first. When it comes to imaging the middle ear is basically just as isolated as the inner ear is.

 

[serendipity1996]

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.

I think you've touched on a really key point that I've thus far struggled to articulate - there does seem to be this dichotomy between the middle and the inner ear. I suppose it's partly a by-product of the highly specialised nature of academic research but it is still slightly frustrating to see as it's difficult to synthesise what this all means. Research into hyperacusis is still in its infancy and only really took off about a decade ago, after Hyperacusis Research was founded, as far as I can tell. The good thing though is that having an organisation like this means that research is more streamlined and the patient's voice is heard. The discovery that the cochlea has pain receptors in 2015-16 has focused much attention on the role of the inner ear (which is fair) and if you look at the conference summaries from Hyperacusis Research from the past few years, much of the focus seems to be on the inner ear. I know this year's annual conference was going to be focused more on the role of the middle ear - it's a shame this couldn't go ahead.

I'm encouraged by much of the research as it's starting to recognise that 'pain' is a fundamental feature of hyperacusis for many people. However, much of these discussions about pain seem to refer solely to the cochlea, e.g. mentioning 'burning or stabbing' in the ears. I have yet to see researchers directly grapple with questions such as 'why do I experience facial pain from noise'? I have wondered if this could possibly be referred pain? I actually went on some TMJ forums and there were many people who experienced substantial ear pain as a result, for example (although not the same as hyperacusis). Dental pain also seems to commonly result in referred pain. So I wouldn't be surprised damage that is maybe originating in the cochlea can cause widespread pain sensations. It could also be a form of secondary hyperalgesia where surrounding tissue becomes sensitised and tissue outside of the injured area reacts to noxious stimuli? The ear seems to be a hotbed of nerves etc and is in close proximity to the trigeminal nerve so this wouldn't strike me as odd.

Paul Fuch's lab is exploring whether the type 2 neurons and the surrounding tissue became hyperexcitable after peripheral trauma and a researcher in his lab is currently doing his doctoral thesis on this. Another postdoctoral fellow in his lab is exploring the impact of cochlear inflammation and type 2 activity as additional factors in the prolonged pain response to sound. So, it's something that is being actively worked on and hopefully this will emerge as published research in the next few years.

Another encouraging thing is that Hyperacusis Research have, for the past few years, turned their attention to setbacks and the physiological mechanisms that could be underlying them. I'm pretty sure Bryan Pollard in his interview with Tinnitus Talk Podcast said that this is now what they are working towards with the researchers. I think setbacks are one of the most frustrating and bizarre aspects of this condition and trying to understand them currently is like an enigma.

I really agree with your frustrations on the shortcomings of some of the current research (as good as it is). I think there is definitely some kind of feedback loop between the middle ear and the cochlea. Something that I was also baffled by in my personal case was that caffeine and stimulants also seemed to exacerbate my facial symptoms. I was kind of confused as to how this could be happening as it is not the result of noise exposure.

However, I came across this from the 2016 ARO hyperacusis symposium: "Important phenomenon: If inflammation is present, sympathetic activity can activate undamaged nociceptors."

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

So, 'sympathetic activity' I take it just refers to stimulation of the nervous system - given that caffeine and some prescription medications are stimulants, could this be why they have tended to trigger my facial symptoms? Just a personal musing.

Looking forward to those models!

 

[grate_biff]

I feel both reactiveness, distortion and pain to my own voice. Especially when I wear my noise canceling headphones. I admit that the higher the frequency, the more there is distortion, screeching and pain involved.

Anyway, it is very interesting (although depressing) following the discussion between you guys @serendipity1996 and @100Hz.
As you may or may not know I´m putting a lot of stock in that my severe noxacusis stems from problems within my MEM and that the pain is trigeminal nerve irritation.

I´m supposed to have my MEM cut next month, but the surgeon wants me to have another try with Spiral Ganglion Nerve blockade first. I already had one using Lidocaine with no effect. This time they will use Botox. Problem is I keep getting my referral denied.

After reading your posts, I too am leaning towards the culprit being within the cochlea. Nocireceptors and what not, but still I am not overly convinced.
Like @100Hz say, it is very strange that if the problems arise because of OHC dying exposing the type II receptors it is very strange this is not a more broad problem within Tinnitus Talk for instance.

In 2014 I had my trauma(s) using headphones. There were short bursts of very loud noise. Almost like gunshots. I was working with editing audio and video.
I developed tinnitus 5 days later in my right ear. I also developed some sort of sensitivity in my right ear, but I could easily handle it. I could still listen to music and go about my day not even thinking about noise other than my piercing tinnitus. My left ear was spared because of a big chump of earwax build up. My right ear was clean as a whistle. It was not until about 3 years after my trauma I would start noticing sound distortion, reactiveness and severe pain to sound. I would have days that were bad, but it would be better again the next day. But slowly over the last couple of years it has become a chronic beast I struggle with 24/7. And it is just as bad in both ears. You both describe the sensation very well and I have it exactly the same way.

I just find it hard to grasp that after all this time my OHC have slowly died and exposed the type II fibers. I find it more reasonable that the constant grief of my tinnitus, the constant stress and anxiety has slowly strained my MEM causing the cluster of symptoms. What do you think?

I will of course be devastated if/when I perform this surgery and I am still left with noxacusis. Either way it is worth shot, right? At least we will be a little wiser as what is what.

All that my testing has showed is that my stapedius muscle really acts up just to low level stimulus sounds, but that could of course be as a reaction to the pain stemming from the cochlear nocireceptor response or it could be an isolated problem of the middle ear it self.

My biggest hope comes from a Facebook group called "Hyperacusis Surgery Success Talk", a couple of members there were cured from what they described as "broken speaker" effect and severe hyperacusis/noxacusis after performing MEM surgery. Their symptoms were not exactly like mine, but pretty close.

I really do not know what to think anymore. Nobody can know for sure.

 

[100Hz]

Here are the models. They're all based on the acoustic shock paper and the cochlea Type II sensitization research. They might be a bit crude and patchy in places but the aim of them is to combine the 2 theories above in various ways.

They take a bit of understanding so may need reading several times and it would help to also read the above papers and research (linked earlier in this thread) for some preliminary background.

They naturally seem to fall into self propelling cycles that could go on endlessly. The apparent 'fuel' for the cycles seems to be inflammation that once subsides is what finally breaks the cycle. The potential triggers for the cycles are more complex and could start in various places.

If there's any obvious errors in these please point them out and I'll fix them if any of it is easily debunk-able then that's good as well as it reduces the number of theories.

In case you've not seen these types of diagrams before, just start at the noise entering the ear and then just follow the arrows, they normally end up cycling in some way.

1.01 - Initial Acoustic Shock Triggered by Cochlea OHC Damage / Type II Sensitization

This model proposes that the acoustic shock is triggered by the sensitization of Type II afferents due to damaged OHC in the cochlea that then send pain signals through the central nervous system back to the middle ear telling it to protect the cochlea. It results in the hypercontraction of the tensor tympani leading to the acoustic shock symptoms cluster. Depending on the severity and duration of the acoustic shock symptoms cluster plus the noxious noise exposure time, there could be a range of damage from no significant lasting damage (acute), to mid ear inflammation leading to possible further cochlea damage (Type II sensitization), through to mid ear inflammation plus trigeminal nerve sensitization. Cochlea inflammation may also stimulate the TGN cochlea nerve endings.

This could explain why people suffer varying degrees of symptoms post acoustic shock, ranging from a seemingly quick and full recovery, to frequency specific noise sensitivity and acute pain, through to delayed lingering facial pain, modulated tinnitus, and setbacks etc. It also assumes that even though there may possibly be no significant mid ear damage as a result of the first acoustic shock, the threat of repeat and more severe setbacks and acoustic shocks remains due to the permanent OHC damage and Type II sensitization in the cochlea, and could also explain the accumulative nature of hearing damage, the worsening of symptoms, and the lowering of threshold for setbacks over time.

If, in this scenario the mid ear and cochlea inflammation were allowed to rest and recover in silence and return to a tolerable (albeit fragile) baseline as indeed they can do, it is perceivable that the threat of setbacks could be neutralized if the damaged OHC can be regenerated with something like FX-322. Other drugs like SPI-1005 and maybe synapse drugs may have further positive effect.

2.01 - Initial Acoustic Shock Triggered by Tensor Tympani Muscle Hypercontraction

This model proposes that the acoustic shock is triggered by the cochlea sending sound signals to the cochlear nucleus / CNS via Type I afferents and not Type II, where it then gets perceived to be a noxious noise resulting in a signal being sent to the middle ear telling it to protect the cochlea. It results in the hypercontraction of the tensor tympani leading to the acoustic shock symptoms cluster. Depending on the severity and duration of the acoustic shock symptoms cluster plus the noxious noise exposure time, there could be a range of damage from no significant lasting damage (acute), to mid ear inflammation leading to possible cochlea damage (Type II sensitization), through to mid ear inflammation plus trigeminal nerve sensitization. In addition to the above damage being done by the acoustic shock symptoms cluster to the mid ear and TGN, the noxious noise (if duration of exposure was long enough) may also now have caused hearing loss, and led to enough OHC damage to cause Type II sensitization directly in the cochlea. This Type II sensitization could now further exacerbate the acoustic shock symptoms cluster, as well as become the potential trigger of frequency specific sensitivity / pain, and further setbacks and acoustic shocks once the initial acoustic shock had been seemingly recovered from. Cochlea inflammation may also stimulate the TGN cochlea nerve endings.

A third causal model could suggest a combination of the 2 above models. Noxious noise causes sensitization of Type II afferents and then proceeds to simultaneously send both pain signals on Type II afferents whilst also sending sound signals on the Type I afferents that are perceived to be noxious and therefore having a synchronized 2 tiered impact on how the acoustic shock affects the mid ear.

These models could suggest that a centralized, heightened neural response to noise may remain even after initial recovery, that now runs independently upon exposure to even non noxious sound. If cochlea damage was repaired by some combination of FX-322, SPI-1005, and maybe also synapse drugs, and the mid ear environment was allowed to also recover, the concern would be that the mid ear response to noise is now heightened and could possibly lead to needless hyper contraction of the TTM and further acoustic shocks at non noxious noise levels resulting once again in mid ear inflammation and TGN stimulation (delayed facial pain). However, to put a positive spin on this scenario, if the cochlea was now repaired and not subject to any further non-noxious frequency specific noise damage/stimulation, this model may indicate that only the mid ear is now at risk of further damage by a newly perceived noxious noise level across all frequencies. It is presumably no longer at risk of damage via frequency specific stimulation of Type II afferents in the cochlea where the damaged OHCs have now been regenerated as presumably, OHC support cells will no longer release ATP. But, if new mid ear inflammation can possibly cause ATP to diffuse through the round window, can this ATP stimulate the previously sensitized Type II afferents or cause repeat OHC damage? The middle ear is also presumably now no longer at risk of setbacks if they indeed do originate in a damage cochlea.

The fact that tolerance to noise does improve as recovery goes on suggests that this is not permanent however.

Of course, a brand new instance of genuinely noxious noise induced cochlea damage remains a possibility.

3.01 - Long Recovery & Repeat Setbacks Now Become A Result Of Noise Exposure To Cochlea & TTM

This model proposes a 2 point effect on possibly why it takes so long to recover after an acoustic shock as well as what could be responsible for setback. In effect there are 2 ongoing conditions running in parallel.

It assumes that once the middle ear has been damaged by an acoustic shock symptoms cluster that it remains vulnerable to any noise. The fact that it is physically moving at all and unable to immobilize and rest and repair leads to a constant state of inflammation that continues to affect the facial muscles, modulate tinnitus, and cause other hearing distortions hence the need to avoid all sound in order to let this damage heal. If there are other reasons why the middle ear may still be active even during silence such as even blinking it could add more reason why it takes so long to recover from the facial pain.

It also assumes that running in parallel are the sensitized cochlea Type II afferents that are still acting as nociceptors upon hearing specific frequencies. This part of the model proposes ATP sensitized Type II's continue to send pain signals to the middle ear to protect the cochlear, and therefore putting an already damaged and inflamed middle ear under even more strain, also raising the likelihood of setbacks and even further acoustic shocks.

This could suggest why tolerance to sound generally increases over time, and why symptoms such as facial pain, modulated tinnitus, and hearing distortions do settle after long recovery periods particularly in silence. Importantly these particular symptoms do not seem to be permanent. It could also explain why certain frequencies cause instant acute pain that leads to repeat setbacks. Finally it could explain why no matter how well recovery seems to be going the possibility of setbacks remain a threat due to the permanent OHC damage and Type II sensitization in the cochlea.

If in this scenario the mid ear and cochlea inflammation were allowed to rest and recover in silence and return to a tolerable (albeit fragile) baseline, it is perceivable that if the cochlea damage can be repaired by a regenerative treatment so that the nociceptors no longer responded to frequency specific noxious noise it would break the setback cycle.

4.01 - Long Recovery & Repeat Setbacks Now Become A Result Of Noise Exposure To Cochlea & TTM & Heightened Neural Responsiveness

This model proposes a 3 point attack on the mid ear due to an already damaged and inflamed cochlea, TTN and mid ear environment, sensitization of TGN, sensitization of cochlea Type II afferents, plus an independent, centralized, and heightened neural response to even non noxious noise.

It firstly assumes that once the middle ear has been damaged by an acoustic shock symptoms cluster that it remains vulnerable to any noise. The fact that it is physically moving at all and unable to immobilize and rest and repair leads to a constant state of inflammation that continues to affect the facial muscles, modulate tinnitus, and cause other hearing distortions hence the need to avoid all sound in order to let this damage heal. If there are other reasons why the middle ear may still be active even during silence such as blinking it could add more reason why it takes so long to recover from facial pain.

It also assumes that running in parallel are the sensitized cochlea Type II afferents that are still acting as nociceptors upon hearing specific frequencies. This part of the model proposes ATP sensitized Type II's continue to send pain signals to the middle ear to protect the cochlear, and therefore putting an already damaged and inflamed middle ear under even more strain, also raising the likelihood of setbacks and even further acoustic shocks.

It further assumes that now there is also a centralized heightened neural response that is running independently upon exposure to even non noxious sound. If cochlea OHCs were repaired by FX-322, cochlea inflammation brought under control by SPI-1005, and the mid ear environment was allowed to recover, the concern with this model remains that the mid ears response to noise is now heightened. This could possibly lead to needless hypercontraction of the TTM and to further acoustic shocks at non noxious noise levels resulting once again in mid ear inflammation and TGN stimulation. However, to put a positive spin on this scenario, if the cochlea was now repaired and not subject to any further non-noxious frequency specific noise damage/stimulation, this model may indicate that only the mid ear is now at risk of further damage by a newly perceived noxious noise level across all frequencies. It is presumably no longer at risk of damage via frequency specific stimulation of Type II afferents in the cochlea where damaged OHCs have been regenerated as presumably, support cells no longer release ATP. But, if new mid ear inflammation can possible cause ATP to diffuse through the round window, can this ATP stimulate the previously sensitized Type II afferents or cause repeat OHC damage once again? The middle ear is also presumably now no longer at risk of setbacks if they indeed do originate in a damage cochlea.

The fact that tolerance to noise does improve as recovery goes on suggests that this is not permanent however.

Of course, a brand new instance of genuinely noxious noise induced cochlea damage remains a possibility.

5.01 - Facial Pain in Setbacks Triggered by Cochlea Trigeminal Nerve Branch Stimulation due to Cochlea Inflammation

This model is quite different. Although similar key elements remain the same such as sensitized Type II afferents in the cochlea and a sensitized TGN, where it differs is how potentially the delayed facial pain is being triggered. It suggests that the cochlea inflammation is what is stimulating the TGN nerve endings in the cochlea which is then in turn causing the facial pain throughout the TGN nerve area.

Such a pathology would suggest that all symptoms (acute frequency specific pain, delayed facial pain, and importantly setbacks) are being triggered by cochlea damage and that drugs such as FX-322, SPI-1005 and possibly synapse drugs would have a very good chance of helping noxacusis in this instance.

6.01 - Post Recovery & Potential Triggers for Setbacks

This indicates that certain symptoms of an acoustic shock or setback do settle over time. Typically, although it can take weeks, months or even years, radiating facial pain as well the middle ear and the tolerance to noise can and do improve.

It assumes however that the TGN remains sensitized and also that the OHC damage and sensitized Type II afferents remain, suggesting that the threat of setbacks and repeat acoustic shocks remains in place. It also assumes that lingering TTN damage could also remain. The degree of likelihood and possibly severity of further setbacks could be relative to the level of damage that the cochlea, and mid ear currently have.

Finally the threat of setbacks being caused by heightened neural responsiveness to noise also possibly remains, however the fact that tolerance to noise does increase over time suggests this also is not permanent and decreases over time if indeed it is even a factor.

 

[xyz]

I just came across this paper

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892385/

It does apply generally to muscles but then probably also to middle ear muscles. There it says inflammation is a key part in muscle regeneration. So could it be that this inflamed / hot feeling is actually something positive as part of regeneration and if one takes NAC this more hinders the muscle regeneration than anything?

Probably I will stop taking NAC and stay with Magnesium.

 

[lapidus]

From October 6.
Investigating the Interaction of Auditory and Pain Pathways

https://hearinghealthfoundation.org...the-interaction-of-auditory-and-pain-pathways

 

[grate_biff]

So, I cut my tensor tympani muscle today. I did the surgery under semi anesthetic. Sedated with Propofol, but still awake. Of course they numbed my ear canal.
Impossible to say if it had any effect on my noxacusis yet as I'm stone deaf due to severe bleeding in the outer ear canal from the patched tympanic membrane. I do not think the severed tendon bleed as much.

I´ll be back later.

 

[Lucifer]

So, I cut my tensor tympani muscle today. I did the surgery under semi anesthetic. Sedated with Propofol, but still awake. Of course they numbed my ear canal.
Impossible to say if it had any effect on my noxacusis yet as I'm stone deaf due to severe bleeding in the outer ear canal from the patched tympanic membrane. I do not think the severed tendon bleed as much.

I´ll be back later.

I hope your recovery goes well and you get a positive effect from doing this surgery.

 

[grate_biff]

I hope your recovery goes well and you get a positive effect from doing this surgery.

Thank you friend

 

[100Hz]

@grate_biff Wishing you all the best my friend, I know you've been after this for ages. I really hope it works for you. Did you ever get the botox stellate ganglion blocker in the end?

 

[grate_biff]

Did you ever get the botox stellate ganglion blocker in the end?

Thanks buddy.

If this doesn't work I will have it. But my surgeon is having trouble finding someone to do it.

 

[JRC1]

Grate_biff, how are you doing?

 

[grate_biff]

Grate_biff, how are you doing?

Not good. It did not seem to help me. I'm devastated and on high doses of Clonazepam.

I think this is probably it for me. I can't wait for FX-322 which may or may not help with severe noxacusis.

 

[JRC1]

Hang in there. I will say a prayer for you. I will pray that happy days (and quiet) are in your future.

 

[100Hz]

@grate_biff So sorry to hear that. Is it still early days though, could it improve?

Stay strong, there's still plenty to hope for in the hopefully not too distant future.

 

[grate_biff]

@grate_biff So sorry to hear that. Is it still early days though, could it improve?

Stay strong, there's still plenty to hope for in the hopefully not too distant future.

I think I would have felt it by now if it was better. The ear has opened up again thankfully, so I can at least try to mask my tinnitus again. I tried for a while with conductive headphones, but it did not really help.
My ear surgeon still think it is a problem in my middle ear, even though I try to tell her about the nociceptors and afferent nerve fibers within the cochlea.

It is weird, I am lying here in bed in a silent room. Still the noxacusis is bothering me. My ears feel so strained and on full alertness just waiting for pain and the ultra high pitch reactiveness to sound. My nervous system is also in high gear from the never ending benzo withdrawal.
I said yes today to be committed for a year on a psychic ward. Maybe it can help me. I have never been more depressed and suicidal. I fear to have less control of noise around me though.

 

[100Hz]

I think I would have felt it by now if it was better. The ear has opened up again thankfully, so I can at least try to mask my tinnitus again. I tried for a while with conductive headphones, but it did not really help.
My ear surgeon still think it is a problem in my middle ear, even though I try to tell her about the nociceptors and afferent nerve fibers within the cochlea.

It is weird, I am lying here in bed in a silent room. Still the noxacusis is bothering me. My ears feel so strained and on full alertness just waiting for pain and the ultra high pitch reactiveness to sound. My nervous system is also in high gear from the never ending benzo withdrawal.
I said yes today to be committed for a year on a psychic ward. Maybe it can help me. I have never been more depressed and suicidal. I fear to have less control of noise around me though.

I can't imagine what you're going through to do that. Stay focused, I'm with you all the way in believing that this was always in all probability down to one of two pathologies, middle ear, or looking more likely now the cochlea nociceptors. As far as setbacks go, most of what noxacusis is, I'm steering more than then ever to the cochlea damage now and at the very least when it comes to possible treatments, SPI-1005 does not look that far away with FX-322 maybe not much further behind.

It's just a matter of waiting now for the drugs to hopefully start coming along to begin trial treating with them, which I believe will need to be accepted as an inevitable part of the process for working out the finer details of noxacusis treatment. Educated research based guesses get us so far, maybe even far enough to put a bit of faith in a theory, but the drugs will be the game changers though when it comes to working it out. Stay strong minded.

 

[xyz]

@futuredreams also already thought about tense muscles in relation to tinnitus / hyperacusis in this thread

Muscular Involvement in Tinnitus/Hyperacusis — Maybe We Can Know More?

I think there is something to it. But what can be done about it? Massaging our jaw muscles and taking large amounts of Magnesium?

 

[weab00]

I can't imagine what you're going through to do that. Stay focused, I'm with you all the way in believing that this was always in all probability down to one of two pathologies, middle ear, or looking more likely now the cochlea nociceptors. As far as setbacks go, most of what noxacusis is, I'm steering more than then ever to the cochlea damage now and at the very least when it comes to possible treatments, SPI-1005 does not look that far away with FX-322 maybe not much further behind.

It's just a matter of waiting now for the drugs to hopefully start coming along to begin trial treating with them, which I believe will need to be accepted as an inevitable part of the process for working out the finer details of noxacusis treatment. Educated research based guesses get us so far, maybe even far enough to put a bit of faith in a theory, but the drugs will be the game changers though when it comes to working it out. Stay strong minded.

I am optimistic too, and I'm also happy to hear you think the evidence is pointing more and more towards cochlear damage the more you research. Just makes you wish our ears could've crapped out a decade from now so we'd have treatments.

By the way, what is the possible explanation for the mechanism behind middle ear issues like TTTS brought on by hyperacusis? Is that the ear trying to protect itself?

 

[100Hz]

I am optimistic too, and I'm also happy to hear you think the evidence is pointing more and more towards cochlear damage the more you research. Just makes you wish our ears could've crapped out a decade from now so we'd have treatments.

By the way, what is the possible explanation for the mechanism behind middle ear issues like TTTS brought on by hyperacusis? Is that the ear trying to protect itself?

Yeh at some point all the research we have to hand, plus our insights into the relationship with our actual symptoms applying to that research will get exhausted and all that's left is to come up with with the most probable cause and the most probable potential treatment. I've got more hope now than I did 5 months when I really started thinking about it, I think hyperacusis is at least on the map now for upcoming treatments.

But definitely it will be a case now of seeing what each drug eliminates as they get released. I can't see how the speculation can go much further now. There are no diagnostic tools of any use, its just a matter of waiting for fresh research to come out and hopefully put more of the puzzle together. At the end of the day the more I think about it the more simple it gets, noise hurts me, there are nociceptors in the cochlea that do nothing except transmit pain signals upon stimulation by noise. It's enough for me for now unless something can blow the theory to peices.

I think TTTS is a residual effect of an acoustic shock for one of two, or possibly both reasons. First I think its partly due to being needlessly activated by heightened neural response to noise, secondly (my own little theory) is that it gets damaged in the acoustic shock and becomes weak and hypermobile making it more 'loose and flappy'. Heightened neural response to noise I believe though is one the symptoms that does recover over time, and becomes retriggered as a secondary response to the cochlea reaction to noise. So again fix the cochlea and hopefully things like neural response will be able to properly recover.

@grate_biff by the way I want to add that I dont think that cutting your tensor tympani is a bad move at all, and could even be part of the whole package that we'll all need in the end. If say cochlea regeneration does work but we are left with heightened neural responses that keep triggering acoustic shocks, the next thing I would do is what you've done. Also don't forget how long it takes takes a damaged middle ear to recover. That surgery must have left a large degree of inflammation behind for now and if that's whats re stimulating your trigeminal nerve it will take some time.

 

[100Hz]

I've read this several times. I understand it bit better every time so I'll see I I can break it down a bit.

Unmyelinated type II afferent neurons report cochlear damage

An experiment was performed where cells were ruptured and from I can get from the research, the supporting cells were deemed to be a major source of ATP acting on type II afferents.

Such immediate rupture of individual hair cells might occur in vivo. More commonly, however, acoustic stress progressively damages OHCs, leading to their eventual death, and is known to increase ATP concentration in cochlear fluids in vivo.

This work provides direct evidence that type II afferents, in addition to sensing glutamate release from OHCs, are activated by cochlear damage in the young rat's cochlea. This observation may help to resolve the decades-long conundrum that type II afferents in vivo are very insensitive to sound and yet presumably carry some information to the auditory brainstem. Likewise, measured ex vivo, synaptic excitation is weak and could activate type II afferents only if all of the presynaptic OHCs were maximally stimulated. Alternatively, ATP potently activates type II afferents and serves as a major contributor to the damage-induced response. ATP can be released into cochlear fluid after tissue stress (even without OHC ablation) in vitro, or noise exposure in vivo.​

I'm a bit confused by the above, I've tried to make some sense of it. It seems to suggest that in vivo or vitro, there is relatively low chance of Type II sensitization, but however if all of the associated hair cells become maximally stimulated then it will become sensitized. But also it alternatively seems to suggest that upon noise exposure, importantly not necessarily leading to hair cell death, ATP could still be released and cause Type II sensitization. I could well be reading this wrong though but it's what it seems to say.

Experimental ablation of OHCs was shown to initiate ATP-dependent calcium waves in nearby Hensen's (support) cells that further triggers release of ATP through their connexin hemichannels. P2X2 receptors have been located to the postsynaptic junction in the OHC region in adult guinea pig, and P2Y2 receptors have been identified in a small population of spiral ganglion neurons in both adult and neonatal rats, suggesting the expression of purinergic receptors in type II neurons.​

I understand that expression of purinergic receptors in type II neurons means the receptors respond to ATP.

Of interest in this context is the previous report that sensitivity to ATP is reduced in type II afferents after the onset of hearing, consistent with the fact that loud sound is not usually painful to normal ears. However, purinergic signaling in the cochlea is up-regulated after noise exposure, raising the possibility that type II afferents become more sensitive after damage, in part by increased sensitivity to ATP.​

This suggests to me that as we know, loud sound for the majority of people isn't painful and that the more the Type II afferents are exposed to ATP, which is more and more frequently after repeat noise exposure, the more they are stimulated by ATP, and then they become more and more sensitive to ATP until they finally become sensitized, at which point they do begin to transmit pain signal upon noise exposure. It seems to not be suggesting that its a one time switch where ATP automatically sensitizes a Type II afferent but cumulative damage.

What I seem to be getting from reading this again, is that it might be suggesting that Type II afferent can become sensitized without OHC death necessarily occurring. If I'm missing something obvious please let me know.

Type I afferents are strongly activated by glutamate release from IHCs, but not by ATP. Type II afferents are strongly activated by ATP, but only weakly by glutamate release from OHCs. These distinctions reinforce the hypothesis that type I and type II afferents serve different functional roles: as acoustic (type I) versus trauma (type II) detectors.

Finally, the KCNQ activator retigabine can silence both type II afferents and somatic pain fibers.​

That experiment you posted last week about the deaf mice still haunts me though because I wish they'd tested what repeat noise exposure would do after the hair cell death, because this question seems to be becoming more prominent now, its obvious that upon hair cell death ATP is released, and according to the above maybe even not necessarily upon hair cell death. What I'd love to know is what kind of activity occurs after the hair cell death. I don't believe Ive ever seen a study showing ATP being released over and over from support cells upon repeat noise exposure, ideally also measuring the specific frequencies used and the support cell response to each individual frequency.

So why does too much noise exposure lead to a setback in hyperacusis sufferers?

@weab00 I'll move this to this thread where it's more relevant.

As per the research and the models arising out of it I assume noise is causing a spark of ATP when it hits the damaged frequency OHC and this is a setback. It's a fact that noise causes setbacks isn't it. And I think this is the start of the chain of events once the integral components have been primed for setbacks (trigeminal nerve sensitization, OHC death, Type II afferent sensitization, possible lingering middle ear damage). As we know loud noise isn't typically painful for most people but once the sensitization thresholds have been crossed, we are not 'most people' anymore and no longer just hear 'loud noise'. Something else is happening, ATP release is my guess.

Noise exposure at specific frequencies / levels aggravates the damaged OHC support cells, they release further ATP, ATP release results in cochlea inflammation plus nociceptors sending pain signals, that results in repeat or further middle ear damage to a possibly still damaged tensor tympani due to the sudden heightened neural response and over activity of the middle ear which then causes mid ear inflammation, mid ear inflammation re-ignites trigeminal nerve related symptoms (facial pain, fluctuating tinnitus, and hearing distortions). Then the recovery process begins again until it all calms down once again, then repeat.

Just trying to make logic of what we've got to work on.

When it comes to sound hitting a healthy cell I draw a parallel with a car driving on the road with tires on. All the components are there for a smooth process. Then say you kill the hair cell, the sound continues to hit support cells which can't handle the sound in the same way so the outcome is completely different and the ATP released is I guess some kind of distress signal resulting in pain. For the purpose of the parallel with the car, image the tires are the hair cells and you now remove them and drive along the road. All the necessary components are not there to handle the process smoothly and would result in other secondary damage to the car. There's probably a better analogy out there.

 

[Aaron91]

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

Really interesting find @serendipity1996.

I was surprised to see this: "Since sensory nerve fibers (e.g., pain, touch) from the face, head, neck and shoulders (facial, trigeminal and spinal nerves) enter the cochlear nucleus, the long-term neuro-inflammation occurring in this region could lower pain thresholds (hyperalgesia). If this were to occur, much lower, moderate-intensity sounds (60-80 dB) might be sufficient to cause hyperacusis (loudness intolerance) with ear pain."

Perhaps this could also explain some of the trigeminal neuralgia symptoms that many of us with this condition experience.

I had been doing a lot of reading about neuroinflammation recently resulting from stress, which I've had a lot of this year and whether that may have predisposed me to developing hyperacusis. The fact this study shows a direct mechanism is very promising to me, as it may suggest that if we can find ways to reduce that neuroinflammation through supplementation - for example, curcumin, resveratrol, quercetin, lion's mane and nicotinamide riboside - then we may be able to help relieve some of our symptoms, unless of course the type II afferent theory really is the main cause and this study is a red herring. I'm currently in the process of putting together a supplement protocol for neurogenesis/nerve fibre regeneration, treating neuroinflammation/auditory cortex inflammation, and alleviating oxidative stress as well as promoting BDNF/NT-3.

This is my current list, starting with many of the obvious:

- Vitamins A, B12, C and E
- NAC
- Magnesium
- Astaxanthin
- Curcumin
- Quercetin
- Lion's Mane
- Zinc
- 100% dark cocoa
- Wheat grass powder
- Seamoss and Bladderwrack
- Niacin
- Resveratrol
- Nicotimanide Riboside
- L-Thianine
- Alpha Lipoic Acid
- Bitter Melon Extract
- Naringin

I'm currently taking about half of these and adding more every few days as I go. I still haven't added resveratrol, quercetin, astaxanthin or Nicotinamide Riboside (among others), which are the ones I'm most excited about from the reading I've done and I've only been on LM for two days so far. I'll also be doing meditation/yoga, as these have shown a lot of promise for overall brain health too.

I'll report back in the next few months.

 

[Marin]

@Aaron91 are you also making any special dietary changes such eliminating dairy or following a keto diet? Just curious.

I have lions mane in my queue and plan to test it out soon. I've also tried many of the other supplements on that list, but for some reason they increase my trigeminal symptoms such as I get increased burning and numbness on my face and neck that can last all day. Anyone have an idea why that might be happening?! It's very frustrating not being able to take any of these potentially helpful supplements.

 

[Aaron91]

@Aaron91 are you also making any special dietary changes such eliminating dairy or following a keto diet? Just curious.

I have lion's mane in my queue and plan to test it out soon. I've also tried many of the other supplements on that list, but for some reason they increase my trigeminal symptoms such as I get increased burning and numbness on my face and neck that can last all day. Anyone have an idea why that might be happening?! It's very frustrating not being able to take any of these potentially helpful supplements.

Yes @Marin, I went completely vegan two weeks ago with the aim of reducing overall inflammation in the body (and hopefully the cochlea and auditory cortex, if there is any). My plan is to give it until end of the year and see how I feel - my understanding is because of the blood-labyrinth barrier it can take a long time to see the effects of all these things (if any). I should note that I've decided not to go with Naringin that is on my list above. While it has been shown to have some promise for neuropathic pain, which was the reason for adding it, it can interact with a lot other stuff by inhibiting liver enzymes (it's basically the key thing in grapefruit juice). I noticed today within half an hour of taking it I was getting minor palpitations, so I'm sure it's interacted with something else I've taken. All in the name of science!

Which supplements are you on?

 

[Marin]

Thanks for the diet info! I'm curious to hear how that works out. I've been trying to eat more healthy fats for nerve health, but just recently got serious about cutting out dairy and grains.

Which supplements are you on?

The only vitamins I'm currently taking are the ones I've been taking for years: a multi vitamin, vitamin C, vitamin D, and vitamin K2.

Everything else that I've tried has given me side effects, and it's incredibly frustrating!

NAC - short of breath and terrible hangover feeling.
Turmeric - fever and skin burning sensation all over
NAD - burning & tingling face, neck, arms
Fish oil - burning & tingling face, neck, arms
ALA - burning & tingling face, neck, arms
CoQ10 - burning & tingling face, neck, arms
Quercetin - burning & tingling face, neck, arms
Resveratrol - burning & tingling face, neck, arms
L-theanine - chest pain

I don't understand why the anti-inflammatory and antioxidant supplements are causing the burning sensations. When I mention it to my doctors they tell me to get an MRI and that is NOT happening.

I do have Lion's Mane and Taurine in my queue to try next, although I won't be surprised if I react poorly to those, too.

 

[Aaron91]

Thanks for the diet info! I'm curious to hear how that works out. I've been trying to eat more healthy fats for nerve health, but just recently got serious about cutting out dairy and grains.

The only vitamins I'm currently taking are the ones I've been taking for years: a multi vitamin, vitamin C, vitamin D, and vitamin K2.

Everything else that I've tried has given me side effects, and it's incredibly frustrating!

NAC - short of breath and terrible hangover feeling.
Turmeric - fever and skin burning sensation all over
NAD - burning & tingling face, neck, arms
Fish oil - burning & tingling face, neck, arms
ALA - burning & tingling face, neck, arms
CoQ10 - burning & tingling face, neck, arms
Quercetin - burning & tingling face, neck, arms
Resveratrol - burning & tingling face, neck, arms
L-theanine - chest pain

I don't understand why the anti-inflammatory and antioxidant supplements are causing the burning sensations. When I mention it to my doctors they tell me to get an MRI and that is NOT happening.

I do have Lion's Mane and Taurine in my queue to try next, although I won't be surprised if I react poorly to those, too.

That's very strange, Marin. I'm obviously not a doctor but fact so many supplements are causing that reaction would tell me that the problem is not with the supplements but that something very peculiar is happening in your body. I can imagine this must all be very stressful for you too. Have you tried magnesium? Has that caused you any issues?

 

[Marin]

Have you tried magnesium? Has that caused you any issues?

Yeah, I've tried magnesium on a few occasions even before this hearing issue, and it gives me headaches and then bad dizziness the next day. I do wish I could take it because it seems like it does a lot of good for people!

 

[100Hz]

Really interesting find @serendipity1996.

I remember reading this find from @serendipity1996 a while back, just read it again to refresh my memory. Its a bit of research that does bother me because it detracts from the 'typical' cochlea pathology that we're hoping will get fixed by upcoming cochlea treatments. i.e. auditory neuropathy as in inner cochlea synapse / SGN connections rather than damage to the auditory nerve external to the cochlea.

One question though, is this referring to the type of damage that Rinri Therapeutics is being developed for? (There's been a bit of discussion lately about it being caused by other conditions such as MS etc. but not typically caused by noise from what I remember. I can't find the exact post I'm looking for from @FGG I think, but there are bits and pieces of discussion in some of the research threads about us noise induced sufferers not really having to worry to much about it.)

If it is anything to do with noxacusis, the timeline could be quite accurate in that it continues to degenerate up to 9 months post noise exposure, but however, it would also seem to be something that can recover to a degree as well unless it is once again inflammation that is recovering and auditory nerve degeneration is something else to add to the list of permanently damaged components.

Would this part of the auditory system be responsible for setbacks though? I would imagine not, and that even though it is damaged (possibly permanently), the susceptibility to setbacks is still more likely to be a fault in the cochlea at a certain point along the frequency range. (For what its worth, although it could be the case that permanent damage has occurred to multiple various components, I would like to think that only one or two of them are actually responsible for setback susceptibility. OHC's and sensitized type II afferents for example. I would hope that if they could be fixed, even though a sensitized trigeminal nerve, damaged auditory nerve, and whatever else remained that at least the threat of setbacks would be over.