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Medical Forum / Diseases and Disorders / Tinnitus / August 2004

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TINNITUS RESEARCH ON ANIMALS? IS IT POSSIBLE?

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Francisco Urbano Garc?a - 26 Jul 2004 08:25 GMT
Hi, I am one more desperate tinnitus sufferer. I understand that one of the
main difficulties to investigate tinnitus is the impossibility of do
research on animals. The reason seems to be that you cannot determine how
the animals feel their tinnitus. Asking Mr. Mice if he feels better today is
not an option. At first that seemed pretty obvious to me too but, the thing
is that I've come up with an experiment design that would allow research on
animals and, therefore, do some investigations that, otherwise, would be
impossible.

I am not an expert on this field so may be researchers already experiment on
animals, or maybe the technique I am about to explain has some flaw. But I
just want to help and I would really appreciate your comments about it.

Regards,

Francisco Urbano Garc?a

/////////////////////////////////////////////////////////

Experiment design to test treatments on animals to improve Tinnitus symptoms

The basis of the experiment rely on training lab animals to recognize
different intensities of noise so that they can recognize different
intensities of tinnitus. One first approach could be like this:

 1.. We get, let's say, 100 lab animals to do a double blind study for
tinnitus.
 2.. The animals will be introduced in a noisy environment with four
different classes of noises:
                                                              i.
Silence.

                                                            ii.      Low
intensity noise.

                                                           iii.      Medium
intensity noise.

                                                          iv.      High
intensity noise.

 3.. The animals will be locked up in a box with just four doors, and each
door will be assigned to a different level of noise. Then, when the animals
want some food they have to choose the right door or, otherwise, they'll get
a little electric charge.
 4.. After some time, the animals will choose correctly the door with food
at all times, avoiding this way the electric punishment. Once the animals
are trained their hearing will be damaged (e.g. chemicals, surgery, sound
explosion. ) in order to produce them a tinnitus.
 5.. Finally, the animals will be left out in their boxes in complete
silence, and every time they choose a door for food they will get it no
matter what.

Therefore, from now on, by studying which door the animal chooses, we will
be able to determined how high its tinnitus is. Now the animal tell us at
all times how its tinnitus evolves. If it is high it will choose the high
intensity door to get its food, if it is cured he will choose the silence
door and so on.

The final stage would be to carry out experiments on half of them to see if
their tinnitus improves compared to the other half.
Smarty pants - 26 Jul 2004 16:02 GMT
> Hi, I am one more desperate tinnitus sufferer. I understand that one of the
> main difficulties to investigate tinnitus is the impossibility of do
[quoted text clipped - 57 lines]
> The final stage would be to carry out experiments on half of them to see if
> their tinnitus improves compared to the other half.

Oh sure, let's give them tinnitus too.  Tinnitus can be induced with large
doses of aspirin.
Jim Chinnis - 26 Jul 2004 16:04 GMT
"Francisco Urbano García" <francisco.urbano@upc.es> wrote in part:

>Hi, I am one more desperate tinnitus sufferer. I understand that one of the
>main difficulties to investigate tinnitus is the impossibility of do
[quoted text clipped - 8 lines]
>animals, or maybe the technique I am about to explain has some flaw. But I
>just want to help and I would really appreciate your comments about it.

Researchers have done research of this type using animals. It is a standard
behavioral science technique. Unfortunately, animal research, especially the
kind that requires training, is very expensive.
Signature

Jim Chinnis / Warrenton, Virginia, USA
Want to discuss Meniere's? See http://groups.yahoo.com/group/MenieresDG

PaulS - 26 Jul 2004 19:52 GMT
There are animal models. Some of the early ones assessed tinntus annoyance
by corrrelating the number of times the animals "pawed their ears" after
aspirin administration with the extent of damage to the ear hair cells.

Some newer animal models have been developed but I have not looked at them
and can't comment. So, here are the links FYI

http://www.sciencedaily.com/releases/2004/04/040407081712.htm

http://www.emoryhealthcare.org/departments/tinnitus/patient_info/patient_guide.h
tml#AnimalModel


PaulS
Francisco Urbano Garc?a - 27 Jul 2004 08:34 GMT
Really interesting. Thank you.

> There are animal models. Some of the early ones assessed tinntus annoyance
> by corrrelating the number of times the animals "pawed their ears" after
[quoted text clipped - 4 lines]
>
> http://www.sciencedaily.com/releases/2004/04/040407081712.htm

http://www.emoryhealthcare.org/departments/tinnitus/patient_info/patient_guide.h
tml#AnimalModel


> PaulS
G. Innipig - 26 Jul 2004 21:45 GMT
> Hi, I am one more desperate tinnitus sufferer. I understand that one of the
> main difficulties to investigate tinnitus is the impossibility of do
> research on animals. The reason seems to be that you cannot determine how

Surely the problem here is that we don't know what causes tinnitus.
Certainly, it may be *induced* with aspirin or a visit to a loud rock
concert, but they are not the general *causes* of it for ordinary everyday
tinnitus sufferers.  I don't take aspirin, and my days of concerts are long
past, yet I am an occasional sufferer.

We can't experiment on animals unless we know what really causes it,
otherwise any findings upon artificially induced tinnitus would be false.
Susan - 26 Jul 2004 21:52 GMT
>Surely the problem here is that we don't know what causes tinnitus.
>Certainly, it may be *induced* with aspirin or a visit to a loud rock
>concert, but they are not the general *causes* of it for ordinary everyday
>tinnitus sufferers.  I don't take aspirin, and my days of concerts are long
>past, yet I am an occasional sufferer.

I think that the fact that the damage tends to be cumulative, re: noise
exposure, your long ago rock concerts could still be the cause.  

>We can't experiment on animals unless we know what really causes it,
>otherwise any findings upon artificially induced tinnitus would be false.

Sure we can.  We don't have to know *how* damage occurs to know that it has
occurred.  In my case, it's related to infectious disease, and responds to
antibiotics, as it did for my child, who was cured of it with antimicrobials.  

The perception of sound is what's studied, even though it has multiple causes.

Susan
been_there_done_that - 30 Jul 2004 15:06 GMT
> Hi, I am one more desperate tinnitus sufferer. I understand that one of the
> main difficulties to investigate tinnitus is the impossibility of do
[quoted text clipped - 57 lines]
> The final stage would be to carry out experiments on half of them to see if
> their tinnitus improves compared to the other half.

Your suggestion is reminiscent of Ivan Pavlov's 'conditioned reflex' study.
PaulS - 30 Jul 2004 21:20 GMT
> Your suggestion is reminiscent of Ivan Pavlov's 'conditioned reflex' study.

Is that bad?

PaulS
been_there_done_that - 31 Jul 2004 01:24 GMT
> > Your suggestion is reminiscent of Ivan Pavlov's 'conditioned reflex'
> study.
>
> Is that bad?
>
> PaulS

No, it isn't bad.  It just came to mind as I read the proposed study on
animals.

btdt
Smarty pants - 31 Jul 2004 02:03 GMT
> > > Your suggestion is reminiscent of Ivan Pavlov's 'conditioned reflex'
> > study.
[quoted text clipped - 7 lines]
>
> btdt

Maybe the government will fund such a study.  After all:

"Just remember it's the birds that's supposed to suffer, not the hunter."

-George W. Bush, advising quail hunter and New Mexico Sen. Pete Domenici,
Roswell, N.M., Jan. 22, 2004
PaulS - 31 Jul 2004 03:41 GMT
> No, it isn't bad.  It just came to mind as I read the proposed study on
> animals.
>
> btdt

Its an interesting notion, at least to me. I wonder if such conditioning can
be used to reduce tinnitus-associated anxiety. Or even if similar mechanisms
are operative using TRT or Neuromonics, etc.

We can exclude Eerie Wax supppositories however. I shudder to imagine what
operant training is going on in that scenario !!

PaulS
Smarty pants - 31 Jul 2004 04:18 GMT
> > No, it isn't bad.  It just came to mind as I read the proposed study on
> > animals.
[quoted text clipped - 9 lines]
>
> PaulS

The EERIE Wax suppositories, roughly the size of codfish head, would be
difficult to administer.
PaulS - 31 Jul 2004 18:28 GMT
"Smarty pants" <bushlies@whitehouse.now> wrote in message news:ncEOc.23$8%

> The EERIE Wax suppositories, roughly the size of codfish head, would be
> difficult to administer.

Geez, then how'd you get them in your ears ;-)
Smarty pants - 31 Jul 2004 21:28 GMT
> "Smarty pants" <bushlies@whitehouse.now> wrote in message news:ncEOc.23$8%
>
> > The EERIE Wax suppositories, roughly the size of codfish head, would be
> > difficult to administer.
>
> Geez, then how'd you get them in your ears ;-)

I'd run the attached string through to the far ear, tie it to a doorknob and
wait.  By the way, I learned the hard way that you have be on the right side
of the door.
PaulS - 31 Jul 2004 23:22 GMT
"Smarty pants" <bushlies@whitehouse.now> wrote in message news:ohTOc.44$8%

> I'd run the attached string through to the far ear, tie it to a doorknob and
> wait.  By the way, I learned the hard way that you have be on the right side
> of the door.

:-)
ENTconsult - 31 Jul 2004 18:17 GMT
Its an interesting notion, at least to me. I wonder if such conditioning can
be used to reduce tinnitus-associated anxiety. Or even if similar mechanisms

most symptomatic T is associated with anxiety reinforcement. Whatever reduces
that helps the patient
EMG biofeedback,
Cognitive therapy
Exercise
Yoga
Xanax
A vacation

whatever breaks the anxiety reingorcement helps.

Murray Grossan, M.D.
http://www.ent-consult.com
PaulS - 31 Jul 2004 18:32 GMT
> Its an interesting notion, at least to me. I wonder if such conditioning can
> be used to reduce tinnitus-associated anxiety. Or even if similar mechanisms
[quoted text clipped - 7 lines]
> Xanax
> A vacation

Murray, true, they all work. But which ones by the principles embodied in
"conditioned reflexes"?

PaulS
ENTconsult - 01 Aug 2004 17:46 GMT
Conditioned refelx is not tinnitus.
when you hear the dinner bell your stomach starts makng digestive juices. When
the alarm clock rings you get up. When the phone rings you pick it up. That's
conditioned reflex.
When the phone rings and you break into a sweat and your heart pounds, that's
not a conditioned reflex. that's an anxiety response modified by your limbic
system.
and if  each time the phone rings, you get more anxious and more nervous,
that's anxiety re-inforcement.

Tinnitus is not a conditioned reflex.
Murray Grossan, M.D.
http://www.ent-consult.com
Jim Chinnis - 02 Aug 2004 02:51 GMT
entconsult@aol.comnospam (ENTconsult) wrote in part:

>Conditioned refelx is not tinnitus.
>when you hear the dinner bell your stomach starts makng digestive juices. When
>the alarm clock rings you get up. When the phone rings you pick it up. That's
>conditioned reflex.

None of those are reflexes. They are sometimes conditioned responses, though.

>When the phone rings and you break into a sweat and your heart pounds, that's
>not a conditioned reflex. that's an anxiety response modified by your limbic
>system.

It can indeed be a conditioned response.

>and if  each time the phone rings, you get more anxious and more nervous,
>that's anxiety re-inforcement.

The anxiety reinforcement occurs only if the phone causes anxiety to be
rewarded. Otherwise, extinction should occur.

>Tinnitus is not a conditioned reflex.

It's not a reflex of any sort. But it could possibly be perpetuated by anxiety
as a conditioned response.
Signature

Jim Chinnis / Warrenton, Virginia, USA
Want to discuss Meniere's? See http://groups.yahoo.com/group/MenieresDG

Smarty pants - 02 Aug 2004 03:40 GMT
> entconsult@aol.comnospam (ENTconsult) wrote in part:
>
[quoted text clipped - 21 lines]
> It's not a reflex of any sort. But it could possibly be perpetuated by anxiety
> as a conditioned response.

Yes, but you can't reinforce a conditioned extinction.
ENTconsult - 02 Aug 2004 16:46 GMT
The anxiety reinforcement occurs only if the phone causes anxiety to be
rewarded. Otherwise, extinction should occur.

Jim, can't agree. Patients are not rewarded for anxiety re-inforcement. Often
it is a crippling life altering condition as the person who can't leave their
home. Probably chemicals are involved since Xanax is ofter therapeutic.
Murray Grossan, M.D.
http://www.ent-consult.com
Jim Chinnis - 02 Aug 2004 17:31 GMT
entconsult@aol.comnospam (ENTconsult) wrote in part:

>The anxiety reinforcement occurs only if the phone causes anxiety to be
>rewarded. Otherwise, extinction should occur.
[quoted text clipped - 4 lines]
>Murray Grossan, M.D.
>http://www.ent-consult.com

I think we're not using the words in the same way, Murray. I think that
anxiety can become associated with tinnitus and a vicious cycle can ensue. I
agree with you that biofeedback and other methods that can reduce the
association can help.

I was just disagreeing with your use of the term "reflex."
Reinforcement of a conditioned response can occur in many ways and not by what
a non-psychologist would call a "reward."

Jim
Signature

Jim Chinnis / Warrenton, Virginia, USA
Want to discuss Meniere's? See http://groups.yahoo.com/group/MenieresDG

been_there_done_that - 02 Aug 2004 18:22 GMT
> entconsult@aol.comnospam  wrote in part:
> I think we're not using the words in the same way, Murray. I think that
[quoted text clipped - 7 lines]
>
> Jim

To further complicate matters, the effectiveness of a reinforcer (reward),
of course, depends on the individual. Listening to loud music is a great
reward for some people; it's punishment for others. Accumulating a lot of
money is critical for some and rather meaningless for others. Likewise,
failure affects us differently. If you are success-oriented, a failure
experience seems to increase your drive to succeed and you will try again to
accomplish the task. If personality-wise you focus primarily on avoiding
failure, a failure is too punishing and you lose interest in the task; you
won't try it again.
It may surprise you but rewards will, strangely enough, sometimes *reduce*
the frequency of the preceding behavior, i.e.,  the effects of punishment.
There is reason to suppose that emotional reactions, thoughts, attitudes,
and physiological processes are also affected by reinforcers.
btdt
Smarty pants - 02 Aug 2004 19:39 GMT
> entconsult@aol.comnospam (ENTconsult) wrote in part:
>
[quoted text clipped - 17 lines]
>
> Jim

There is a single stimulus, the onset of tinnitus, and a response to that
stimulus.

If the response to the onset of tinnitus is anxiety leading to examination
by a qualified professional to rule out an acoustic neuroma, it is useful.
I say the anxiety response is conditioned by knowledge, reinforced by
encouragement or (shudder) suppressed by drugs.

People don't anticipate the onset of tinnitus and don't develop (condition)
a targeted response.  In my opinion they respond as to a burn or a broken
arm.  Their response will depend on inherited qualities and life
experiences.  Some will just deal with it, some will go over the edge.

As we've observed here, the onset of tinnitus is sometimes associated with
other trauma; related or coincidental, real or imagined.   Nobody ever said
participating in a support group was easy.  :-)

Bill
PaulS - 02 Aug 2004 04:35 GMT
> Tinnitus is not a conditioned reflex.
> Murray Grossan, M.D.
> http://www.ent-consult.com

Agreed! I was suggesting a role for conditioned reflexes (or associative
learning or operant conditioned, etc.) in tools/processes used to reduce
tinnitus-associated anxiety.

PaulS
Smarty pants - 02 Aug 2004 05:46 GMT
> > Tinnitus is not a conditioned reflex.
> > Murray Grossan, M.D.
[quoted text clipped - 5 lines]
>
> PaulS

From what I've experience, the anxiety is worse than the noise.  Overcoming
anxiety is a necessary step toward habituation.  Anxiety is best reduce
through acceptance.  Acceptance is gained through knowledge.  Know it won't
kill you.  Know there isn't a cure.  Know habituation is possible.
been_there_done_that - 02 Aug 2004 16:38 GMT
> > > Tinnitus is not a conditioned reflex.
> > > Murray Grossan, M.D.
[quoted text clipped - 10 lines]
> through acceptance.  Acceptance is gained through knowledge.  Know it won't
> kill you.  Know there isn't a cure.  Know habituation is possible.

Behaviors that are classically conditioned are those which involve the
learning of involuntary responses -- responses over which the learner has no
control and to which he or she responds reflexively or "automatically."

In classical conditioning, behaviors are increased in one of two ways:
1.  repeated practice and positive reinforcement: more pairings (of neutral
stimuli with unconditioned stimuli), which can include drill-and-practice
(i.e., additional training) but also includes rewarding the desired
behavior, positive reinforcement (e.g., trying to build an association
between desired behavior and pleasure of the reward)
2.  stronger reinforcement: stronger unconditioned stimuli (i.e., traumatic
events) produce stronger conditioning

There are several ways to change inappropriate conditioned responses:
1.  extinguishing: stop pairing the response with the stimulus in order to
extinguish the linkage (this is the mildest method, and least reliable
because of speed, avoidance, and spontaneous recovery)
2. counter conditioning: replacing one conditioned response with a new, more
beneficial conditioned response (tends to be more effective than extinction,
also decreases chance of spontaneous recovery of previous conditioning);
includes two forms, depending on desired outcome
3.  eliminating the response to the stimulus: through *systematic
desensitization*, where the object is to eliminate the response -- classic
treatment for phobias and other anxiety responses using the *threshold
method*  of presenting the stimulus so faintly at first that the individual
doesn't respond to it in the habitual manner -- then increasing the
intensity of the stimulus so gradually that the individual continues to
*not* respond
4.  exhaustion: keep repeating the stimulus until the individual is too
tired to respond in the habitual way; the intent is to get the response to
the stimulus to become "doing nothing" or "not responding" to the stimulus.

Classical conditioning is a major factor in real life. It's a fundamental
part of all forms of animal training (including some forms of human
training). Its primary use in human behavior is in dealing with habit
formation, either trying (1) to form good habits (enjoying exercising,
positive thoughts vs. negative thoughts, for ex. "My tinnitus will *never*
allow me to lead a normal life....replaced with "My tinnitus will *not*
control me.", creating a persistent, positive environment, etc.) or (2) to
break bad ones (listening to loud music, being a victim of self inflicted
worry or anxiety, etc.), including phobias or anxiety-producing
conditioning.

Yes, you are correct, Murray.  Tinnitus is NOT a
conditioned reflex.  Pavlov's study was just a parallel observation.  Those
who suffer from tinnitus-associated anxiety (conditioned reflex) *could*
benefit
from behavior changes, cognitive therapy, medication
(when medical necessity is established), knowledge, etc. But, most
importantly....only through acceptance will these various methods be
beneficial.

btdt
ENTconsult - 03 Aug 2004 08:02 GMT
counter conditioning: replacing one conditioned response with a new, more
beneficial conditioned response (tends to be more effective than extinction,
also decreases chance of spontaneous recovery of previous conditioning);
includes two forms, depending on desired outcome

In EMG biofeedback we have the Tinnitus be the stimulus to relax
Murray Grossan, M.D.
http://www.ent-consult.com
PaulS - 03 Aug 2004 02:03 GMT
> From what I've experience, the anxiety is worse than the noise. Overcoming
> anxiety is a necessary step toward habituation

Oh so right you are!

> Anxiety is best reduce  through acceptance.  Acceptance is gained through
knowledge.
> Know it won't kill you.  Know there isn't a cure.  Know habituation is
possible.

Acceptance helps and is essential but not sure I agree that active
acceptance is the initial stimulus to habituate. Most can't will themselves
to accept it. They have to experience the fact that tinnitus will not kill,
will not interfere with certain  activities (e.g., sex). Then that
experience, no matter how small, reinforces the habituation process and
reinforces acceptance. Some positive experience, I think, must occur first.

PaulS "Pavlov Reincarnated"
Smarty pants - 03 Aug 2004 02:34 GMT
> > From what I've experience, the anxiety is worse than the noise. Overcoming
> > anxiety is a necessary step toward habituation
[quoted text clipped - 14 lines]
>
> PaulS "Pavlov Reincarnated"

We agree Paul.  I think those "positive experiences" you mention tend to
sneak up when we aren't expecting them.  Certainly there were many times
when I didn't notice my tinnitus before it dawned on me that I was
habituating it.  In fact, I remember the day that I first realized I hadn't
noticed it for a while and finally appreciated the effectiveness of
distration.
Patty - 03 Aug 2004 04:27 GMT
> > > From what I've experience, the anxiety is worse than the noise.
> Overcoming
[quoted text clipped - 26 lines]
> noticed it for a while and finally appreciated the effectiveness of
> distration.

I suppose I'm on my way to habituation as I have longer periods of 'not
noticing' my tinnitus.  I've accepted tht it isn't going to kill me, there
is no cure, and I don't dwell on it... as I once did.  I use my own masking
techniques and they seem to be helping.  I remain hopeful that I, too, will
someday not hear it for MUCH longer periods.  Thank you Bill and Paul for
all the advice and caring enough to offer suggestions.
~Patty~
PaulS - 03 Aug 2004 04:57 GMT
> I suppose I'm on my way to habituation as I have longer periods of 'not
> noticing' my tinnitus.  I've accepted tht it isn't going to kill me, there
> is no cure, and I don't dwell on it... as I once did.  I use my own masking
> techniques and they seem to be helping. .

Baby steps, right :-)

> I remain hopeful that I, too, will someday not hear it for MUCH longer
periods

You will!

> Thank you Bill and Paul for all the advice and caring enough to offer
suggestions.

Well, I think Bill and so many others would agree that we've been there, and
occasionally fall back, but having support is important. So giving it is an
easy thing to do.

Geez, I'm getting that Kumbaya feeling....yeech ;-)

PaulS
PaulS - 03 Aug 2004 04:51 GMT
"Smarty pants" <bushlies@whitehouse.now> wrote in message news:pYBPc.14

> We agree Paul.  I think those "positive experiences" you mention tend to
> sneak up when we aren't expecting them.  Certainly there were many times
> when I didn't notice my tinnitus before it dawned on me that I was
> habituating it.  In fact, I remember the day that I first realized I hadn't
> noticed it for a while and finally appreciated the effectiveness of
> distration.

Bill, I only hope that "newbies" read what you just wrote. The process is
subtle as you indicate and takes some time.

PaulS
ENTconsult - 04 Aug 2004 07:19 GMT
the fact is that you can't have anxiety if your muscles are relaxed. That's why
you put sensors on the muscles to measure electrcal output. If you can reduce
the electrical output your muscles are relaxed adn no anxiety. that's why EMG
biofeedback works.
Murray Grossan, M.D.
http://www.ent-consult.com
ENTconsult - 02 Aug 2004 16:52 GMT
Agreed! I was suggesting a role for conditioned reflexes (or associative
learning or operant conditioned, etc.) in tools/processes used to reduce
tinnitus-associated anxiety.

EMG biofeedback works well for this.

By way of explanation
you can scratch because it itches
or you can have treamendous anxiety because it itches, and the more you scratch
the more it itches, etc.
This is exactly what happens when the New Yorker who lives on the lower floor
apartment with sirens and traffic all night drives to Chicago and stops at
Motel 6 where it is absolutely quiet. Suddenly he hears Tinnitus. If he goes
into an anxiety re -inforcement response then the T gets worse. He may cancel
his trip and head back home and the delay in seeing a doctor may make him even
worse.
Murray Grossan, M.D.
http://www.ent-consult.com
ENTconsult - 31 Jul 2004 18:14 GMT
Any study that has to do with hearing can help in tinnitus research.
Murray Grossan, M.D.
http://www.ent-consult.com
 
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