@Diesel, I agree with the OHC theory. It's the one I most want to be true but regarding noxacusis as a result of acoustic shock, I'm going to expand on it a bit. I also agree that acoustic shock causes NIHL at a rapid pace, but I believe acoustic shock causes far more damage than just NIHL. I hang onto these 3 possibilities below.
1. Type II afferents are activated when outer hair cells are damaged and cause noxacusis. Fix the OHCs with FX-322 and then in theory connections and sensory input are restored. FX-322 is potentially the full fix for noxacusis sufferers who didn't get it through acoustic shock.
This is also good to know (quoted from the link below)
'Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage'. So the new retigabine is also a possibility I hope.
https://www.pnas.org/content/112/47/14723
2. Based on the acoustic shock symptoms cluster, the point that stands out for me is the devastating chain reaction of inflammatory and destructive processes that get kicked off at the outset of the shock, only one of which is possibly the destruction of OHC's and sensitization of type II's. Notable points below are taken from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/
'The middle ear inflammation [resulting from the acoustic shock] is associated with the secretion of many proinflammatory molecules and may lead to earache and otalgia (tingling and stabbing pain).'
'To note, the inflammatory molecules present in the middle ear cavity may cross the round window and cause inner ear damages (hearing loss), in particular in the high frequency region. One can further speculate that these molecules (such as ATP) may further reach the organ of Corti and activate the unmyelinated type II afferent neurons synapsing with OHC'.
'Finally, ATP and other proinflammatory molecules, produced in the middle ear during inflammatory processes and diffusing up to the Organ of Corti, may activate cochlear type II fibers and trigger sound-induced earache. One notes that ATP may also be released by the OHCs that are damaged due to the acoustic shock or trauma or due to the cytotoxic effects of proinflammatory molecules that diffused from the middle ear. Assuming that the diffusion of ATP secreted in the middle ear is limited to the cochlear base, sound-induced earache may be produced by high-frequency sound, which is consistent with informal patient reports.'
'Tinnitus that follows an acoustic trauma has been reported to fluctuate over time, in close correlation with tingling in the ear and otalgia' (Noting this because it exactly matches my tinnitus / hyperacusis relationship).
Here's the important bit where I'm a bit more skeptical about FX-322. It
could break the cycle by repairing OHC's, and certainly could deal with some otalgia, but if any other resulting nerve pain (from the acoustic shock, not the type II's) remains ongoing due to being a separate self sustaining process then I think a separate nerve pain management drug is also needed. The link above goes deep, but from what I can relate to in it, and regarding your question 'what makes it any more unique than gradual NIHL?' I'd say the answer is that
many more independent sensitization's of different nerve systems appear to take place during an acoustic shock. NIHL is only one single offshoot of the cluster of symptoms
. My biggest question in this scenario should I only take FX-322, is would any nerve pain still present be sensitive to noise any more? I might be happier that even though there was still various nerve pain left, at least now it might not be noise sensitive anymore.
3. Synapse disconnection. Hopefully OTO, Hough or Pipeline could also potentially be a fix if this causes noxacusis.
There are more theories that involve genetics and the fact that some people may be more predisposed to noxacusis, but until I can ever try these drugs It's enough for me now to have faith in them working and in my genetics.
Bottom line is, no one knows, I could be wrong about everything, but it doesn't hurt to try and do a bit of working out. I'm not negative about any of these drugs, they all sound promising. I'm trying to (with what precious little knowledge we have) build up hope that what's in the research pipeline will benefit noxacusis sufferers in as many of the various scenarios as possible because we need some hope. I have far more hope for solely hearing loss and tinnitus sufferers. If I was suffering from either or both of those conditions without noxacusis then I'd be confidently waiting for the upcoming drugs.
I like your posts, I read lots of them but respectfully, this one quoted was out of place seeing as you're on here obviously as a sufferer of something hearing related. I don't think it's fair to say with regard to acoustic shock
'It seems to be thrown around like it's a special cause of hearing loss; and somehow those who experienced it will need some special treatment.' This just sounds like you personally are bored of hearing the term and it comes across as dismissive. It could almost be something I'd expect from a doctor. I'm pointing this out in the friendliest way possible, I'm not aware of what you suffer from, but this is what I suffer from.
Acoustic shock leading to life changing noxacusis is a horrific and instantaneous turning point in someone's life. There's nothing gradual about it, and it does not get
thrown around lightly. I've spent most of the last several years in pain, in bed, in silence, reading about all the potential upcoming drugs for hearing loss and tinnitus wondering where the F*** does pain hyperacusis come into the picture. One of the only things I have left in life is to read what I can and try and decipher the web of the potential causes, pathologies, symptoms, and treatments to fit noxacusis into the equation, luckily after lots of reading and very helpful input from here I'm optimistic and I think one way or another, as long as the drugs get successfully released, noxacusis will be covered. I hope this offers a little bit of optimism anyway.