Pain Hyperacusis in Relation to Acoustic Shock & Synapse Disconnection

I don't even remember what the jaw things feels like anymore, but sometimes now I get a fullness in my neck, so that went away and something else replaced it.

 

Ah, sorry to hear about your neck. Did you do anything to make the jaw thing go away or did it just go away on its own?

 

It went away on its own. I remember the exact moment the neck thing started - I was listening to ultra-high frequency bimodal stimulation and the nerves in my throat started feeling full. Now it's reproducible any time I do that as weird as it sounds.

 

I was able to do this with ACRN and my face would feel full. Like my sinuses were getting congested.

 

Wow, what an incredible post! You are a ridiculously clear thinker. I intentionally fully quoted this post, big as it is, so as to repeat it for people who are new to this thread.

I think a good way of summing up your theory is that it's essentially "tendinitis of the ear." I've unfortunately dealt with my fair share of tendinitis (tendinosis to be specific), and my pain hyperacusis behaves exactly the same as it/how your diagrams spell out. The threat of getting worse again is always there after a long period of rest and lowering (or even disappearance of) inflammation. Once injured, it seems, our bodies are never truly the same.

When, say, your wrist develops tendinitis, once way in which you make sure that you never relapse again is to strengthen up the surrounding muscles, "supporting" the injured area. I wonder if there's an analogue for our ears? Probably not, considering it's not mechanical/muscular...

 

I was just looking at papers on tendinitis based off your post and the post you quoted. I think it’s a good analogy, but I’m wondering about what I’m reading here when you guys discuss inflammation:

Treatment of Tendinopathy: What Works, What Does Not, and What is on the Horizon

“Recent basic science research suggests little or no inflammation is present in these conditions. Thus, traditional treatment modalities aimed at controlling inflammation such as corticosteroid injections and nonsteroidal antiinflammatory medications (NSAIDS) may not be the most effective options.”​

So with if this is the case, does that mean all the focus on here about reducing inflammation may not play as great a role in recovery from noxacusis related to the middle ear?

Anyone with further insight it would be great if you could weigh in on this.

 

I'm the same, it's really annoying not knowing what exactly is causing the pain.

 

I also have the stiffness feeling in and around the ears... I'm having a setback after two years. Is the stiffness better for you now?

 

@100Hz, what do you think about ototoxicity in how it relates to noxacusis and recovery? You mentioned acoustic shock. Does ototoxicity work the same?

 

It has improved. I have the feeling that 24/7 hearing protection loosens up those ear muscles and thereby improves hyperacusis. I have also read elsewhere here that tense ear muscles are related to hyperacusis.

 

How long did it take to improve? I'm 4 months in from having a setback after 2 years. I don't have tinnitus or hearing loss. It's just that tight feeling...

 

I'm not who you asked but I had a few setbacks recently and each time it took about 1 or 2 months to start getting better and then very slowly getting better from then on. Tolerance to noise went up but not that much, hence the setbacks again.

 

Improvement takes time in the order of years. Hyperacusis without tinnitus is quite uncommon. I had 13 years tinnitus before I got hyperacusis.

 

I had hyperacusis without tinnitus for 4 years. My hyperacusis got progressively worse over the years, then turned much worse after 3 years and I got tinnitus at that time too.

 

@100Hz hasn't posted here in a long time. I fear the worst.

 

I didn’t realize that. Hope @100Hz is okay.

 

Hey, this is probably a long shot but would you be able to tell us more about their symptoms? Did they have acute, stabbing like pain, or burning?

 

Is the acute stabbing pain more related to the inner ear than the burning? I always thought the burning was more tensor tympani muscle or trigeminal nerve related.

 

If I have to make a guess, yes.

I believe I saw your post inquiring about getting Ambroxol in Canada. Why not give ApoHealth a shot? For just over 10 EUR you can get 50 tablets shipped to your country within 6 to 10 business days. Worst case scenario, customs seizes the product and you'll lose a couple bucks.

 

So this thread is interesting. I see the mention of calcium blockers helping with noxacusis. I still reckon BHV-7000 and XEN1101 are more likely to help with hyperacusis/noxacusis due to it being potent in targeting Kv7.2 and Kv7.3 where it can calm the synapses and suppress the type II fibers causing us pain. No idea whether we would have to take it long term or not.

 

I ordered the Ambroxol a while back. It arrived in Canada earlier this month, I still haven't heard anything though. I'll give them a shout soon.

I've heard various people say Ambroxol is ototoxic. I'm not sure whether I want to try Epidiolex or Ambroxol first, given that the former isn't ototoxic from what I recall. Though I'm a bit worried about taking it with possible visual snow.

 

I think you are saying this on the basis of the 'hype' surrounding Kv7.2/7.3 channels on Tinnitus Talk, and not on a deeper understanding of how ion channels work. I don't mean this the wrong way but if you are going to suggest that not-yet-available drugs are going to be more effective than medication that we can already try out, you should at least give some solid arguments.

You say that BHV-7000 and XEN1101 will be better (in all senses of the word) drugs for treating noxacusis as if that is something self-evident. It is not. The evidence of Retigabine helping with pain hyperacusis at the normal dose range is actually very scarce studying the User Experiences thread. Same story for Flupirtine and cannabidiol. Sorry to burst your bubble.

Unless you present some arguments that display at least to some extent an understanding of pharmacological principles, I think it's a bad idea to make claims like this, especially in this context particularly as we are talking about an entirely different ion channel. I believe the concept of a 'miraculous' noxacusis drug is dangerous because it breeds passivity in regards to trying other drugs out, and might encourage reckless behavior in regards to noise exposure. It also creates unreasonable expectations which might be dramatically crushed eventually.

I used to be guilty of overhyping Kv7 channel modulators as well, thinking they were the final solution to our noxacusis. Kv7 channel openers are just a means to an end, namely to prevent the membrane potential of type II SGNs (and maybe other cells) from depolarizing above the action potential threshold. There are multiple ion channels and receptors involved with the membrane potential of a cell, and we don't know the full extent of their implication in type II spiral ganglion neurons, let alone hyperacusis as a whole. And even if we would know, that still doesn't necessarily tell us which drugs would be the best, also in regards to side effects, toxicity and whatnot, in treating hyperacusis.

So instead of passively waiting god knows how long on drugs that may or may not pass FDA approval, and may or may not be appropriate in treating hyperacusis, we should focus on the reality at the present moment and try to actively figure out which already existing substances could treat help us with our hyperacusis.

This wasn't directed to you specifically. I really want to heal from noxacusis as fast as possible. I've suffered enough already. Drugs which treat hyperacusis already EXIST. It's the task of our community to find out which drug, or combination of drugs, can help us make our lives livable again. I don't know about you but I'm already far past the point where I can expect just hearing protection to significantly improve my condition. With each setback recovery becomes more unlikely. So we cannot afford to wait.

 

I definitely agree that we don't know 100% if these potassium channel openers will fully help with our condition, nevermind which type of noxacusis it will help and to what extent.

Though I'm trying not to get my hopes up, the fact that some people with noxacusis had some sort of benefit with these potassium openers (Retigabine, Flupirtine, Epidiolex, Gabapentin), along with the 2015 study, gives me a little hope that we're on the right track.

I really understand why people aren't so willing to try current medication for this, besides Epidiolex and Gabapentin, there's not really much medical evidence that other drugs will help with this. For me, the pain isn't bad yet, so I'm trying to wait as long as possible before trying anything that might worsen my symptoms. The first thing I'll probably try if it gets bad is Epidiolex, it should be available in Canada soon.

When do you think we'll start seeing XEN1101 or BHV-7000 get released for compassionate use?

 

I’m not sure but I feel like Biohaven’s BHV-7000 will more likely offer compassionate use than Xenon Pharmaceuticals due to it being bought out by Pfizer but who knows.

Even though these Kv7 potassium channel drugs are for epilepsy, they are also testing it out for depression and pain so very unlikely a doctor would say no to prescribing these drugs.

 

I see people mix up terminology on here a lot, but noxacusis refers to the nociceptive system in the inner ear, in other words pain coming from excited type II SGNs. Correct me if I'm wrong, but what you've probably seen is self-diagnosed hyperacusis patients reporting relief. There is not a single mention of the term 'noxacusis' in the Retigabine User Experiences thread. Maybe I've misread it but I tried to search for the term 'pain' in that thread and I could not find anyone mentioning suffering from acute stabbing pain. If I recall correctly, I have only seen one person on here reporting some relief from Gabapentin, but the analgesic effects wore off after a couple of days. Obviously my experiences with cannabidiol were unsuccessful too.

Bluntly said, the problem is that the majority of the people on here are just repeating snippets of information they've read here and there without any critical thought, and then presenting that as self-evident facts. Again, if people are going to say that calcium channel blockers will be more effective than potassium channels openers, than they should at least provide some arguments or evidence for that.

Besides that, in order to treat our hyperacusis we are probably going to need some sort of multimodal drug therapy. I've been through it all; countless of supplements, laser therapy, Flupirtine, cannabidiol, none of that shit works on its own. Going through each of the treatment options one by one is probably futile anyway. See my post here.

 

I agree with you that no one in the Trobalt User Experiences thread mentioned the term noxacusis so we are uncertain if it can help or not. Maybe they were getting hyperacusis mixed up with reactive tinnitus which are completely different things. It would have been better if there was a way to contact the people who experienced hyperacusis to ask which type they had. I suggested @Markku to email them to see if they can answer us.

But right now there are no drugs that can help with noxacusis and increase LDLs. Some of these drugs that are out can’t be taken long term or the effects don’t last.

As much as I want to believe in other theories on what is causing hyperacusis/noxacusis, the next thing on our list that may help us are the Kv7 potassium channel modulators; BHV-7000 and XEN1101. Obviously there is no guarantee that these will work with noxacusis and increase LDLs but they are the only things that are next on our list.

 

It's funny, earlier I quoted a post which said that two people with pain hyperacusis were helped with some type of medication, and here you are saying that "there are no drugs that can help with noxacusis and increase LDLs".

We know of at least one person that had acute, stabbing pain hyperacusis who was helped with Clomipramine.

Burning pain is helped by Ambroxol.

Some people were helped with Flomax.

Gabapentin is already available to try.

Megan Wood is currently investigating the role of inflammation in pain hyperacusis.

I've already identified multiple drugs that could help us which have never been tried before for pain hyperacusis. I know a guy who has his own laboratory.

And I'm not even talking about the possibilities of combining different drugs yet.

You are saying that drugs that we already have access to, including some which have helped alleviate hyperacusis for some people, are somehow worse options than drugs which are still in the clinical phase, will take god know how long to become available, and haven't even been tried for hyperacusis in the first place? If you are going to say that "some of these drugs that are out can’t be taken long term", don't talk about things like early access or compassionate use.

Again, on the basis of what arguments do you think a new potassium channel modulator is somehow superior to what we already have? On the basis of the results reported in the Retigabine User Experiences thread you try to assess the probability of BHV-7000 and XEN1101 helping with hyperacusis. You are forgetting that Retigabine acts on Kv7.4 as well. KCNQ4 is expressed on outer hair cells, which connect to type II afferents. Do you know how a changed excitability of outer hair cells is going to affect the response of type II SGNs to sound? Are you aware that ribbons on outer hair cells increase in number and volume after damaging sound, and what that means for hyperacusis?

Your posts give me the impression that you have a very shallow understanding of the subject matter.

In the last few weeks I've spent countless hours reading and trying to understand my condition and possible treatments. I've tried Flupirtine and cannabidiol myself at no small cost, both financially and mentally. I am telling you that simply waiting around for XEN1101 or BHV-7000 to become available and trying no other drugs in the meantime is a DUMB idea.

Hyperacusis is a super complex phenomenon. In my opinion, XEN1101 or BHV-7000 won't be enough on their own to treat, let alone cure noxacusis, and we are wasting precious time just sitting around and doing nothing. People can do with that information what they will.

 

If there are drugs that help with noxacusis/hyperacusis right now, can you please tell what those drugs are, describe what the patients' hyperacusis/noxacusis were like, can they tolerate more noise after taking the drugs, and can they take the drugs long-term or did they have to stop taking the drugs after a while?

 

I have mentioned them in the very post you quoted. In the Clomipramine and Flomax threads you can find the specifics. If I wasn't a little convinced they could help with noxacusis, I would not have name dropped them. Why wouldn't you try them out if I may ask?

If you are really convinced that XEN1101 or BHV-7000 will help treat noxacusis, have you made sure that expanded access is not available yet? Maybe you could send them an email?

 

I know Xenon Pharmaceuticals aren’t offering compassionate use. Biohaven might when they start the pivotal phase but who knows. I don’t live in the USA/Canada so expanded access won’t be available to me. I will have to wait for these drugs to come out before trying.

Hopefully someone from Canada and USA can get access to these drugs. Xenon Pharmaceuticals is in Canada and Biohaven/Pfizer in the USA.