Ca(2+)n You Feel the Noise?

[HighleyTall]

Prove me wrong.

Lidocaine can knock out the hair cells temporarily and thus stop the calcium waves (or partly -> changing pitch) depending on the dose.

 

[StoneInFocus]

What do you mean by the last bullet point?

 

[HighleyTall]

There is feedback between OHCs and IHCs called the medial olivocochlear (MOC) efferent feedback system. OHCs control the tectorial membrane to be able to focus on a sound (like a voice in noise or listening to what the trumpet is doing in music). But because OHCs are damaged in a frequency region, the IHCs are telling the OHCs to focus more. Maybe they are hyperactive, and thus, you perceive sound louder or even more painful as they act as nociceptors. Or maybe because there are dead OHCs in a frequency region (and unable to control the membrane), movement is too strong for the remaining OHCs in that frequency region, and thus sends warning signals. Steriocilia of OHCs are also embedded in the membrane and move much less than those of IHCs. They move mainly on (very) loud sounds.

You probably also only perceive hyperacusis in a region with still working IHCs.

BTW, I'm thinking out of the box, not following Jastreboff's narrative with wearing blinkers.

 

[StoneInFocus]

But because OHCs are damaged in a frequency region, the IHCs are telling the OHCs to focus more.

Who says that?

 

[Note]

Damaged OHCs, swelling and vacuolization of myelin sheaths (auditory nerve), neural hyperactivity in the DCN, hypothalamic inflammation, blocked potassium channels, HCN2 as a key ion channel driving tinnitus.

How do these theories fit together?

 

[BB23]

I have no outer hair cell damage and I have hyperacusis. DPOAEs are fine. No hearing loss either. I had dysacusis for the longest time but it went away completely, thank God.

Does that prove you wrong?

 

[HighleyTall]

Who says that?

The brain

Damaged OHCs, swelling and vacuolization of myelin sheaths (auditory nerve), neural hyperactivity in the DCN, hypothalamic inflammation, blocked potassium channels, HCN2 as a key ion channel driving tinnitus.

How do these theories fit together?

I'm not saying there is no swelling and vacuolization of myelin sheaths (auditory nerve).

Some (f)MRI meta-analyses throw a lot of these papers into the bin. If you experience tinnitus, there will of course be neural activity.

Maybe it is in most cases an auditory nerve problem (acoustic neuromas can cause tinnitus too, for example).

How do you explain improved (32%) or even disappeared (45%) tinnitus after Schwannoma surgery? Or how tinnitus disappeared in 101 patients, and improved in 43 patients after neurectomy of 151 patients (Pulec 1963 - 1993)? Seems to me he had better results than we have now with TRT, CBT, TMS, or medication...

Barotrauma and acoustic trauma are very similar.

Alshabory et al.

Patients with tinnitus might have neural dysfunction at either the level of the cochlea, as shown in reduced DPOAE levels, and changes in the normal DP-I/O function recorded in the present work.

In conclusion, patients with tinnitus might have neural dysfunction at either the level of the cochlea, of the auditory nerve, or of the brainstem. In the present work, we indirectly assessed the integrity of the afferent auditory pathway by using DPOAEs in tinnitus cases with normal hearing. The results showed that those affected by tinnitus show reduced OHC activity, as detected by reduced DPOAE levels and change in the normal DP-I/O function, which may manifest as tinnitus even before there is a shift in the hearing threshold.

 

[HighleyTall]

Updated version

We need a P2X7R channel blocker: JNJ-54175446.

 

[StoneInFocus]

The brain

Do you want to have a serious discussion or not?

What you are saying is largely incomprehensible to me and my reading comprehension is well above average.

I don't think anyone here understand what you mean, sorry.

No offense.

 

[dd314]

How do you explain improved (32%) or even disappeared (45%) tinnitus after Schwannoma surgery?

Do you have a source for this? I looked into this a few years ago and I remember the results were all over the place.

 

[HighleyTall]

Do you want to have a serious discussion or not?

What you are saying is largely incomprehensible to me and my reading comprehension is well above average.

I don't think anyone here understand what you mean, sorry.

No offense.

Sorry about that. But this made me think. Maybe hyperacusis is just a macro-mechanical problem.

A function of the OHCs is to suppress the movement of the tectorial membrane on loud noises. If stereocilia of OHCs are ruptured due to an acoustic trauma, they cannot suppress the tectorial membrane anymore. Thus, IHCs get more signal, and you perceive sounds louder. The more damaged OHCs -> the more tectorial membrane movement -> the more IHCs signal (perceived louder than normal).

In this theory you can have a deaf ear (complete loss of IHCs) but experience hyperacusis in that deaf ear if there are still functional OHCs. You can have tinnitus with perfect hearing (almost no IHCs lost) but damaged OHCs (causing nerve innervation, nociceptors). You can have very bad hearing (a lot of lost IHCs) but not experience tinnitus and hyperacusis if you didn't encounter extreme noise causing a lot of OHC damage.

My father was a carpenter, at 88 he had a very bad hearing but he never experienced tinnitus or hyperacusis. He never encountered extreme loud noises, just long-time loud noise exposure and thus only degeneration of IHCs.

I have a distant family member, she has a very bad audiogram. She only has very mild tinnitus, I don't know about hyperacusis, maybe mild too. If you have mild hyperacusis, you are probably not really aware. At least I wasn't.

If you were to pinch the cochlear nerve, don't you think this would show up in an fMRI in brain regions?

→ This is the paper regarding Schwannoma surgery.

When removing tissue on a nerve, the nerve can still be damaged and thus still cause tinnitus. I also read in a paper the method used to remove it can have different results in post-operative tinnitus.

Neuropathic pain is very hard to treat. Recent research (McNaughton) also link tinnitus to neuropathic pain.

I have no outer hair cell damage and I have hyperacusis. DPOAEs are fine. No hearing loss either. I had dysacusis for the longest time but it went away completely, thank God.

Does that prove you wrong?

No. Because you can have perfect hair cells (no IHC damage) and yet have hyperacusis.

 

[HighleyTall]

Update:

If tinnitus is a cochlear nerve problem, this could also explain why I started to feel tingling on skull and face in the summer of 2023. This is now daily. Maybe the facial nerve is enervated too. And just very recently, I sometimes feel dizzy in bed when I'm awake at night. Maybe the vestibular nerve is starting to get enervated too? Not to mention burning ears...

Besides it is very logical for nature to build in a warning system in the OHCs and not the IHCs for extremely loud sounds. The OHCs protect you from extremely loud sounds, namely they temper the tectorial membrane.

 

[HighleyTall]

Sounds are probably not even processed much louder to the brain by the IHCs. You just get an uncomfortable feeling and can get pain from louder sounds, because the OHCs act as nociceptors; it is a warning system. There is a threshold shift because the leftover OHCs are more under stress and thus send the signal sooner. You get the same warning when you still have perfect hearing and stand next to a very loud speaker. You will start to FEEL you have to move.

This doesn't mean you can't improve. But dead hair cells are gone forever:

Mammals have a reduced capacity for intracellular repair of hair bundle damage. Recovery of tip links and the actin core provides a clear example of a possible contributing factor to the recovery from temporary threshold shift, while inefficient repair of hair bundle damage, such as F-actin core depolymerization, or the death of hair cells likely cause progressive and permanent hearing loss.

If type II afferents (OHC) are equivalent to nociceptors, it could be the reason why we perceive tinnitus and hyperacusis independent from IHC loss.

This would explain why you can have tinnitus but have a perfect audiogram. You can have hyperacusis (the uncomfortable feeling and even pain) + tinnitus in a deaf ear. IHCs are lost but you still have partly functional OHCs. A barotrauma probably causes more damage to the OHCs (these are more susceptible to damage). You can still have a pretty good hearing (a flat lowered curve) but because of damaged OHCs, you experience tinnitus.

From my experience tinnitus and hyperacusis go hand in hand.

When I first experienced tinnitus, I couldn't imagine having to live with this for the rest of my life. But I adapted in a few months. I had to start wearing earbuds playing music because it felt a little uncomfortable. But restaurants etc. weren't a problem. This only changed later on.

Someone who has exposed themselves to loud noises all their life, but not to extreme sounds causing a lot of OHCs loss, will not experience tinnitus or hyperacusis.

If you have very local OHC damage (a small frequency range), you are probably not going to experience hyperacusis, but you can perceive tonal tinnitus. This could also explain why some experience specific sounds of certain frequencies as annoying or uncomfortable.

Please discuss. Or are we just going to keep following Jastreboff for another 50 years without any results?

Voltage-dependent potassium channel openers KCNQ consisting of benzanilides, (III), prepared by McNaughton-Smith were effective in treating migraines and related diseases modulated by potassium channel opening agents.

McNaughton is the man to watch!

Interview with Prof. Jos Eggermont:

When a person with tinnitus asks you if there will ever be a cure, and when that might be, what do you answer?

Yes, there will be a cure, but that will not be found in the next decade. I always tell them that since aetiologies differ, clinical trials often turn out negative but that there are always some people who benefit, and not only from a placebo effect.

To illustrate this, I here tell my own story. I used to have chronic tinnitus and blame it on my military service, albeit it did not develop until I was in my early 60s. Note the "I used to have". Being recently diagnosed with high blood pressure, I was suitably provided with a whole cocktail of medications. I noticed that my daytime tinnitus was more or less completely obliterated after I took my medication. Note that it is present when I wake up. This medication regimen includes a calcium blocker, and I recalled that Jastreboff used to put a similar drug into the drinking water for his rats, which abolished tinnitus-related behaviour. I don't know if there has ever been a clinical trial with that (and it may not be good for everyone).

Interesting. I take medication for hypertension too...

 

[HighleyTall]

If efferent type II are nociceptors (Nowak 2021), maybe the sound itself is not processed louder (through IHCs) than normal to the brain. It just becomes uncomfortable because OHCs trigger the 'warning' too soon. If the sound is louder, OHCs are triggered more and it becomes pain (noxacusis). Just like it will for someone with 'healthy' OHCs, but just at a much higher dB level.

Maybe hyperacusis patients just THINK they perceive it louder, but it FEELS like it is louder and can experience pain.

So there is just a SHIFT because of OHCs with more and larger ribbons.

I get the startle reflex when, for example, a spoon hits porcelain. Not because it is louder but because the OHCs give the 'warning' signal at much lower dBs.

Meaning there doesn't need to be a higher output at the IHCs or there doesn't have to be 'brain amplifying' .

At first (when mild) you are not even aware, you just notice that louder sounds are becoming uncomfortable (just like older people sometimes complain about louder sounds, they SEEM to perceive it louder). The threshold is shifted just a bit. And it keeps shifting over the years along with from (heavy) noise exposure because more and larger ribbons at the OHCs.

And what if there isn't a broken amplifier in the brain but just a set of 'broken' sensors (OHCs)?

The early triggered OHCs (because of more ribbons) at a smaller vibration making the brain think the noise is loud (the OHCs telling there seems to be a lot of movement going on, which is not the case).

Thus the efferent type I -> medial olivocochlear feedback tells the brain to amplify the IHC input.

This sounds like hyperacusis and noxacusis to me.

 

[HighleyTall]

And now read the Discordant theory.

 

[Note]

And what's the reason that hyperacusis often improves after a few months?

 

[HighleyTall]

And what's the reason that hyperacusis often improves after a few months?

Good question.

When auditory hair cells are killed, they are gone for good, but the new UVA research shows these delicate cells can repair themselves from "sublethal" damage caused by loud noises or other forms of stress.

Mammals have a reduced capacity for intracellular repair of hair bundle damage. Recovery of tip links and the actin core provides a clear example of a possible contributing factor to the recovery from temporary threshold shift, while inefficient repair of hair bundle damage, such as F-actin core depolymerization, or the death of hair cells likely cause progressive and permanent hearing loss.

And perhaps the younger you are, the better your chances are.

I actually have a distant family member in his early 20s who experienced hyperacusis as very uncomfortable and he recovered but still is left with mild hyperacusis and now uses earplugs in loud environments.

But hyperacusis will probably only get worse over the years. There is natural hair cell degeneration after 50 years.

 

[Nick47]

Not just tinnitus-related. However, tinnitus is listed as something improved in long-term COVID-19 patients who took calcium channel blockers.

In females, Ca channel blocker administration, rather than having hypertension, was significantly associated with reductions in the frequency of alopecia (OR 0.14, 95% CI 0.03-0.67, p = 0.015), memory impairment (OR 0.14, 95% CI 0.02-0.82, p = 0.029), sleeping disorders (OR 0.17, 95% CI 0.04-0.67, p = 0.012), tinnitus (OR 0.23, 95% CI 0.05-0.98, p = 0.047), sputum (OR 0.31, 95% CI 0.10-0.92, p = 0.035), and fever (OR 0.33, 95% CI 0.12-0.93, p = 0.036).

→ Calcium channel blockers may reduce the development of long COVID in females

 

[Note]

I took Lasea for a month. It did nothing for my tinnitus and not much for my anxiety.