Pain Hyperacusis in Relation to Acoustic Shock & Synapse Disconnection

I wonder what the consequences of having smaller/larger ribbon sizes are? Would I be right in guessing that a larger ribbon size would mean there's a greater chance of synapsing the OHCs to the type II afferents?

I've been giving more and more thought to this inverse relationship Fuchs alluded to between the type 1 and 2 afferents post noise exposure. I want to bring to everyone's attention this passage from the zebrafish study:

"decreasing voltage-gated Ca2+ influx through CaV1.3 channels during development led to the formation of ... larger ribbons. Furthermore, in mouse knockouts of CaV1.3, auditory outer hair cells have reduced afferent innervation and synapse number."

For those who don't know, a knock-out mouse is a mouse that's been genetically engineered to not have a particular gene by disrupting it with a piece of artificial DNA. So these mice were genetically engineered to not have the voltage-dependent calcium channel and the result was less afferent innervation and synapse numbers, suggesting that the calcium channels play an important role in regulating the synapse numbers. If we know from the recently released Fuchs study that synapse numbers of OHCs increase after noise exposure, this would suggest that noise exposure disrupts the function of the calcium channel in the complete opposite manner than that seen in the knock out mouse. I also recall from Liberman's work that IHCs in the high frequency region of the mouse cochlea have enlarged ribbons immediately after noise, followed by synapse loss.

So where I am going with this? In short, I am inferring that the dysfunctional Cav1.3 calcium channels may be the smoking gun here with regards to what's causing our hyperacusis. I've had a quick look online to see what other diseases and conditions are caused by dysfunctional Cav1.3 calcium channels and the biggest one seems to be Parkinson's, which is sometimes treated with calcium channel blockers. Interestingly, the zebrafish study has something to say here:

"Recent work in mice has investigated the role of the MCU in noise-related hearing loss. This work demonstrated that pharmacological block or a loss of function mutation in MCU protected against synapse loss in auditory inner hair cells after noise exposure".

I just wonder: could a calcium channel blocker, such as a Parkinson's-prescribed drug, help us with our symptoms?

Would love to get some feedback on this and I again encourage everyone to read this zebrafish study!

 

Hi Friend,

So sorry you're suffering.

When do you think you would go to the hospital?

I'm praying for you buddy.

Daniel

 

There is a long waiting list I'm afraid. The noxacusis is killing me. I need some medication. Maybe I should try Lyrica. I have not really read anything positive about it, but it is supposed to ease nerve pain. Benzos and Oxycontin don't really work anymore either. I'm back on benzos regularly as well. I'm a nervous wreck. I'm on Prednisolone which does not really calm me down either.

 

I think you guys are reading too much into the inverse relationship between the synapse types. Correlation does not equal causation.

 

Hyperacusis Research's upcoming webinar looks like it will be focusing on the mechanisms of noxacusis and interestingly seem to be splitting the condition into 2 separate areas. Middle ear and cochlea. This is great news because it looks like they may be exploring the possibility that there are 2 pathologies that could be interrelated.

• Arnaud Norena from France, discussing how injury to middle ear muscles may lead to inflammation.

• Megan Beers Wood of the Paul Fuchs lab at Johns Hopkins University in Baltimore, discussing novel findings that show how pain signaling nerve fibers are altered by noise.

https://fundraise.hyperacusisresearch.org/event/2020-hyperacusis-research-benefit-webinar/e312504

 

I will try and catch this when it's on, I hope there will be closed captioning!

 

So sorry brother.

I wish I could help you... honestly.

Why Prednisolone? Isn't that a steroid?

I think drugs are great if they work, shame the benzo doesn't help... What about Dr. Shullman's protocol of Gababentin (spelling) and Clonazepam? He is listed on a thread devoted to his protocol.

I don't know about Lyrica.

Sorry I am not more helpful. I know you are in pain.

Please stay in touch and let us now how you are doing.

Take care friend,
Daniel

 

Thank you for caring @Daniel Lion

Anybody knows if the TN is involved in the Type II fiber theory?

Could Lyrica possibly help?

I'm on Prednisolone because they have found something in my brain in an MRI. I was hoping it would do something with a possible inflamed cochlea or brain stem, but it did nothing to ease the pain.

I should contact Frequency Therapeutics begging them to make me a special project, but what is the chance of that?

Severing my Tensor Tympani muscle was really my last chance. It did nothing with the pain.

 

I don't know, this type II extra synapse finding raises a load more questions. We don't know if the additional synapses can reduce in number again.

Also what is the difference between sensitization and these additional synapses, or are they the same thing? Is this what sensitization is? I'm still of the understanding that sensitization is permanent whatever the case, and I'm only thinking it through but the only other variable that would relate to the pattern of 'recovery' would be inflammation, again inflammation is said to last for many months in the cochlea (and I'll take an educated guess that the same goes for middle ear inflammation) which also bears relation to the long recovery time. It could be a combination of the 2 though, it's good that there are some real targeted questions to answer coming out of this now at least.

I don't think inflammation causes the increase in type II synapses. I think that is down to either the IHC synapse losses (although I'm skeptical about this relationship), or more likely the OHC bundle become 'maximally stimulated', which again raises the question of if this could actually be type II sensitization taking place.

I do believe though at certain frequencies where the critical damage is, that this is what releases excess ATP upon certain frequency noise expose and causes inflammation which then takes time to fade away and stop aggravating the type IIs again. Loads of questions still, but I think it's in the right area now.

I will get into that zebrafish research when I've got a bit of time.

This I agree with, at least for part of noxacusis underlying pathology. I will do a ultra high frequency audiogram done at some point as I'd like to see if it shows anything.

 

I read yesterday on the forum that Lyrica is good for nerve damage... do some research... might be a winner.

We keep searching and trying to find something that works...

You've been dealt a tough hand there...

I am sending you love and hugs.
Stay well and PM or write me here anytime.

Peace out,
Daniel

 

A summary of the 2020 ARO Symposium focusing on hyperacusis - this was held before the pandemic struck so presumably at the start of the year. Megan Beers Wood's research (of the Fuchs lab) about the increase in type 2 ribbon synapses is mentioned (although it's just a brief summary so nothing we don't already know from the paper)

"It appears that, contrary to Inner Hair Cells, which show a loss of ribbon synapses, Outer Hair Cell ribbon synapses actually increase after noise exposure. This has significant ramifications for a possible mechanism of hyperacusis."

https://hyperacusisresearch.org/2020-aro-research-2/

 

Another interesting bit of research that was discussed was Richard Salvi's:

"Rich Salvi’s lab developed a novel reaction-time model where faster reaction times correlate to increasing levels of sound sensitivity after noise-induced hearing loss. Most importantly, this is also frequency dependent, which is an important factor in humans who often experience dramatic differences of impact depending on the frequency, or pitch, of sound exposure."

Perhaps his research could offer insights to those of us particularly afflicted by hyperacusis that worsens when exposed to certain frequencies.

 

I have that too lol.

 

The synapse proliferation finding is still anxiously puzzling.

 

Yeah, it is. At least we can reasonably assume a synapse drug should help with loudness hyperacusis since Liberman believes it's due to synapse loss (and given most of us with pain also have loudness, according to Bryan Pollard, it's nice to know we could get 1/2 of these taken care of at least lmao). We will find out more about noxacusis soon enough, I hope.

 

I find it so interesting that most have both and yet both potentially have different pathologies. It really makes me wonder if there’s a relationship between the two. I guess we’ll find out soon enough.

 

That, but what I almost find more fascinating is that I seem to be the only one in this entire forum that has hyperacusis due to an infection and not noise exposure and therefore cannot get excited over regenerative medicine since they almost always handle acoustic trauma.

 

Yes, that's something that intrigues me. And it's interesting how the researchers talk about it - Liberman talks about them being essentially two completely separate entities. Fuchs says that "There is probably a progression in hyperacusis from an initial condition where louder sounds become more irritating or annoying, to then becoming increasingly painful."

I do think it can sometimes be quite hard to separate the pain and loudness when you have both just from my personal experience.

And to add to that, most people with hyperacusis will also have tinnitus as well. It seems rare that you'd just get one of these pathologies "in a vacuum". They all stem from acoustic trauma but it will be good to gain more insight into the particular mechanisms of each.

 

Well couldn’t the infection have damaged the chohlea? Regenerative medicine doesn’t only help noise damage, I think it’d help anyone whose problems comes from hair cell or synapse loss.

 

I mean I hope so lol, the pain has been quite severe these past 3 days.

 

Ever try a benzo?

 

Hyperacusis is just one part of the larger acoustic trauma/noise injury equation. There's also reactive tinnitus, dysacusis, trigeminal sensitization, VSS, radiating neck pain, migraines, etc. It also seems to me that hyperacusis is an umbrella term for different pathologies, like cochlear damage vs. neurological stuff like concussions and autism. Subtyping would be a big breakthrough for the condition, although I imagine we'll have good treatments long before we properly understand hyperacusis itself.

 

Bro, I went to the hospital yesterday crying of pain, and they flat out told they have no idea, in a top rated clinic in BERLIN, they gave me something intravenous and referred me to a psychosomatic shrink. That's it.

 

So did anyone else catch the Hyperacusis Research webinar?

 

I imagine many here couldn’t listen to it. I definitely can’t. Anything big?

 

There was closed captioning available for those unable to listen - I definitely wouldn't have been able to listen via audio haha.

 

Reading these hyperacusis theories has made me so anxious. So when inner hair cells are damaged there's a loss in IHC ribbon synapses whereas if the outer hair cells are damaged there's an increase in OHC ribbon synapses.

I thought increasing synapses will improve hyperacusis. I do hope FX-322 improves pain hyperacusis.

 

I missed it! I had been looking forward to it too, oops.

 

Yeah the synapse thing is a big 'WTF' moment. All of this talk does make me anxious that the mechanisms for hyperacusis don't line up with those for curing hearing loss, but the argument for a cure is a very convincing one. So I just reassure myself and keep faith, so to speak, even if it's a cognitive bias.

 

I caught the webinar and thought one of the more positive aspects is that with acoustic trauma, the middle ear can have all sorts of weird inflammation involved with it that takes a long time to slowly calm down. Meaning one should not think the worst possible scenario. It also showed that this is not a linear process. It may explain why some people get better at different time frames. Also interesting was the animals that had loud exposure for 2 hours (around 110db), although they had inner ear damage to hair cells and synapses, they also had significant hearing loss - so a 30db sound now needed to be played at say 60db for the same affect. I took from that if you have no significant hearing loss then maybe that’s also a positive with ones outlook on recovery. This was also a snapshot of events on these animals, so no answers were given on the state of their ears after x amount of time.