More on Achalasia opioid hypersensitivity

[Guest guest]

" We think that further studies on peripheral opioid agonists in achalasia

patients may be of interest for two reasons. First, they may help to ascertain

whether the receptors involved in morphine hypersensitivity are located within

or outside the central nervous system. Secondly, as pharmacological treatment is

relatively inefficacious and not well tolerated, they may indicate whether it is

worth testing a small oral dose of a peripheral opioid agonist [morphine]in

combination with a calcium channel blocker or nitrate in order to achieve a

greater reduction in lower esophageal sphincter tone by combining two different

relaxation mechanisms. "

Interestingly in the study, naloxone - an opioid antagonist you wouldn't want to

take - either increased LES pressure or had little effect. These results

strongly suggest a link to opioid hypersensitivity in achalasia.

And those of you with NCCP, spasms and poor appetite will have these symptoms

greatly ameliorated by properly conducted opioid pain management - without the

need for notoriously inefficacious traditional GI approaches.

Again, much of my intent strives to provide rational, scientific bases and

reverse the moral stigmas in social and medical communities for the legitimate

use of opioids in achalasia, and other forms of moderate-to-severe chronic pain.

Read the whole pdf in gut.bmj.com by googling morphine and achalasia.

Your pain management enlightenment advocate,

Steve

[Guest guest]

Steve wrote:

>

> " We think that further studies on peripheral opioid agonists in

> achalasia patients may be of interest for two reasons. First,...

> Secondly, as pharmacological treatment is relatively inefficacious and

> not well tolerated, they may indicate whether it is worth testing a

> small oral dose of a peripheral opioid agonist [morphine]in

> combination with a calcium channel blocker or nitrate... . "

>

Being that they suggest further studies are needed to determined these

things it is implied that they are not saying they have demonstrated

these things to be true, but only that their findings support these

possibilities. One thing to keep in mind was that the study was not

long-term. One problem with other pharmacological treatments is that

they become less effective over time. One possible reason that

achalasics may be hypersensitive to opiods is that the normal path for

creating and delivering endogenous opioids to the LES muscles is broken.

In time after delivering pharmacological opioids to those muscles they

may stop being hypersensitive. The response that was up regulated in the

absence of opioids may be down regulated once they are continuously, or

frequently, supplied. Studies are needed to know for sure. I assume you

can tell us how long such treatment has worked for you and we can hope

that if we need them they will work at least that long for us, but I

don't see any guarantee that they will work the same for everyone.

>

> And those of you with NCCP, spasms and poor appetite will have these

> symptoms greatly ameliorated by properly conducted opioid pain

> management - without the need for notoriously inefficacious

> traditional GI approaches.

>

Once again, " those of you with ... will have " should be " SOME of you

with ... MAY have. "

We are not all the same. Some NCCPs are not the types that would benefit

from opioids. We don't all have the same LES pressure. Mine was over

100mmHg after swallows. A drop of only 11mmHg as suggested by that very

small study would have been far to little to help me. Some people don't

have elevated pressure at the LES and may even have a somewhat low

pressure. They just have a failure of it to relax. 11mmHg could be a big

improvement for them. Also, achalasia is progressive. Some people have

more of a normal response still intact while others do not. It should be

noted that the response to morphine in the study was paradoxical in

achalasia patients and that in normal subject opioids actually cause

problems swallowing and in both achalasia and normal they cause other GI

problems. In fact, in normal subjects morphine reduces LES relaxations

after swallows not improve them.

For more on what opioids do the people without achalasia see:

Opiate-induced oesophageal dysmotility.

http://www.ncbi.nlm.nih.gov/pubmed/20003176

A Patient With Dysphagia Associated With Opioid Medication

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325310

> Again, much of my intent strives to provide rational, scientific bases

> and reverse the moral stigmas in social and medical communities for

> the legitimate use of opioids in achalasia, and other forms of

> moderate-to-severe chronic pain.

> ...

> Your pain management enlightenment advocate,

>

It is sometimes nice to have an advocate, but please don't misrepresent

us or the science in your efforts to advocate for us.

notan

[Guest guest]

>

.. One possible reason that

> achalasics may be hypersensitive to opiods is that the normal path for

> creating and delivering endogenous opioids to the LES muscles is broken.

The study hypothesized the effect was not to due to denervation, and that the

receptors responsible may be in the LES or other locations.

> In time after delivering pharmacological opioids to those muscles they

> may stop being hypersensitive. The response that was up regulated in the

> absence of opioids may be down regulated once they are continuously, or

> frequently, supplied.

The concept of tolerance wasn't addressed. For pain, once a therapeutic dose is

achieved the response is long-lasting. Compared to traditionally used agents -

such a botulinum toxin which has a very transitory effect or the calcium channel

blockers which have unpredictable effects, opioids are known for their

stability.

>Studies are needed to know for sure.

Yes, we need more long-term studies. And I encourage the National Institute of

Health to conduct more in this field that is wrought with personal prejudice and

scientific irrationality. In terms of their use, however, opioids used in

methadone maintenance have a documented track record of safety and efficacy,

along with providing remarkable functional improvements.

>I don't see any guarantee that they will work the same for everyone.

There isn't a guarantee any treatment will work the same for everyyone. But

currently, GI will pursue the same approaches for achalasia, and dictate what

the results should be - not necessarily from the patients' perspectives. So,

mechanically manipulating the LES may be an outsider's basic method of

addressing achalasia, but it doesn't even begin to treat all the other symptoms,

such as appetite, NCCP, spasms, anxiety, etc.

> Once again, " those of you with ... will have " should be " SOME of you

> with ... MAY have. "

I certainly wish my GIs had used those qualifiers... Many people here are

looking for options after having their concerns dismissed by doctors or being

pushed into treatments that offer little benefit.

> the response to morphine in the study was paradoxical in

> achalasia patients

I'm addressing the opioid hypersensitivity to achalasia patients, not " healthy "

people. It should be noted that the administration of naloxone, a strong opioid

atagonist, immediately increased LES pressure in the achalasia patients,

suggesting a mechanism unique to this group.

>

> Opiate-induced oesophageal dysmotility.

> http://www.ncbi.nlm.nih.gov/pubmed/20003176

>

> A Patient With Dysphagia Associated With Opioid Medication

> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325310

A study with one patient? The key main side effects of opioids on the GI tract

are nausea and constipation, both of which dissipate with time. All the decades

of methadone maintenance have yet to elucidate any such significant health or

cognitive problems.

Steve

[Guest guest]

Steve wrote:

>

> notan wrote:

> >. One possible reason that

> > achalasics may be hypersensitive to opiods is that the normal path for

> > creating and delivering endogenous opioids to the LES muscles is

> broken.

>

> The study hypothesized the effect was not to due to denervation, and

> that the receptors responsible may be in the LES or other locations.

>

What the study actually said was, " This finding is unlikely to be the

result of a denervation process involving opioid nerves. " That does not

say it was not the result of denervation. They say in the paper that one

possible explanation " is impairment of non-opioid nerves located between

the opioid receptor and the lower oesophageal sphincter muscle, ... " and

another is an " abnormal compensatory neural mechanisms... . "

> The concept of tolerance wasn't addressed. For pain, once a

> therapeutic dose is achieved the response is long-lasting. ...

>

Long-lasting effect. (Look below before responding).

> The key main side effects of opioids on the GI tract are nausea and

> constipation, both of which dissipate with time.

Effects dissipates with time.

So, the effect on pain remains but the effect on those GI symptoms

dissipates. The LES is part of the GI system. What would be your guess

for the LES effect? I think more studies are needed. Now, if other

options were not working I would take this study as hope that some

opioid treatment could work if I needed it, but I don't think that it is

enough to overcome popular resistance to the idea.

> Yes, we need more long-term studies. And I encourage the National

> Institute of Health to conduct more in this field that is wrought with

> personal prejudice and scientific irrationality. In terms of their

> use, however, opioids used in methadone maintenance have a documented

> track record of safety and efficacy, along with providing remarkable

> functional improvements.

>

I also wish they would promote more studies on cannabinoid drugs. The GI

system has cannabinoid receptors and there are many cannabinoid

substances. Not all of them are mind altering. Seems like there is

potential there but it is politically unpopular.

>

> There isn't a guarantee any treatment will work the same for

> everyyone. But currently, GI will pursue the same approaches for

> achalasia, and dictate what the results should be - not necessarily

> from the patients' perspectives. So, mechanically manipulating the LES

> may be an outsider's basic method of addressing achalasia, but it

> doesn't even begin to treat all the other symptoms, such as appetite,

> NCCP, spasms, anxiety, etc.

>

SOME, GI will pursue the same approaches for achalasia. Probably most,

but there do exist some that are willing to work with patients who don't

want to fallow the dilatation/myotomy path. There are members of this

support group that have chosen not to go that route and have doctors

working with them. I went six years after being told I should have a

myotomy before I did. My doctors were happy to let me take that waiting

option, even the surgeon, who I didn't see until the sixth year and she

didn't care if I continued to wait. I can't say they would have been as

willing for others in other situations but they thought it was in my

case my choice. As doctors are often accused of pushing drugs I can't

imagine that if I had asked for a pharmacological treatment that they

wouldn't have offered something and worked with me to find what worked

for me.

> Many people here are looking for options after having their concerns

> dismissed by doctors or being pushed into treatments that offer little

> benefit.

>

As with many things, one needs to shop to get the best option. That may

include shopping for a doctor.

> I'm addressing the opioid hypersensitivity to achalasia patients, not

> " healthy " people.

>

I don't think it is that black and white. Some of us are more " healthy "

l than others so millage may vary.

> It should be noted that the administration of naloxone, a strong

> opioid atagonist, immediately increased LES pressure in the achalasia

> patients, suggesting a mechanism unique to this group.

>

" Naloxone had no effect on resting lower oesophageal sphincter pressure

or swallow induced relaxation in either healthy subjects or achalasia

patients. " But, it reversed the effect of morphine on the LES.

> > Opiate-induced oesophageal dysmotility.

> > http://www.ncbi.nlm.nih.gov/pubmed/20003176

> >

> > A Patient With Dysphagia Associated With Opioid Medication

> > http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325310

>

> A study with one patient?

>

It does say that right in the title and that would mean it had just 9

less achalasia subjects than the study you gave us. But to the point

that opiates cause problems swallowing in normal patients, such as

failed LES relaxations, we have 10 from your study (failed relaxations),

15 from the first study and 1 from the last for a total of 26. Not a lot

but we started with just 10 from your study. There may be better studies

out there, these were easy to find. If this is typical then more studies

are needed to show otherwise before one can say there is not a problem.

> ... All the decades of methadone maintenance have yet to elucidate any

> such significant health or cognitive problems.

>

One drug in a special application not related to people who have

achalasia. Granted, not much is studied for problems in patients with

achalasia. Which means this all goes to making an educated guess. Which

to me seems to be what achalasia and treatments are about. However,

there are more statics related to achalasia for dilatation and myotomy

than there are for opiates. There may be more statistics for opiates in

healthy people than for standard achalasia treatments, but how well do

they apply to achalasia is also a guess. Take the opiate data and make a

guess. It will be your guess and not everyone has to guess the same.

Which is why they practice medicine and not even doctors agree on all

things.

notan

[Guest guest]

> But currently, GI will pursue the same approaches for

> achalasia, and dictate what the results should be - not necessarily

> from the patients' perspectives.

I agree with Notan that there is significant variability among doctors, and

shopping around is crucial.

Our primary care doc, after getting my SO's achalasia neatly diagnosed in a

couple of weeks, told us from the beginning that pharmacological treatment was

an option. He warned us that for most people it either doesn't work well enough,

or stops working well enough over time. But he has several achalasia patients

who have done well long term with drug treatment alone. They still have some

limitations (e.g., one can't go out for a big steak dinner anymore), but they

are happy where they are and happy to avoid invasive treatment.

Nitrates worked quite well for my SO for a while, but not after a while. We

don't know if that's because her achalasia progressed or because she adapted to

the drugs, or both.

It is true that both big shot GI specialists we interviewed expressed nothing

but scorn for drug treatment of achalasia. One said he won't even use it

anymore. Our more open-minded primary care doc did (to us) the right thing and

laid out all options as he understood them and left the decisions to us. Finding

the right docs to work with could not be more important.

> > >. One possible reason that

> > > achalasics may be hypersensitive to opiods is that the normal path for

> > > creating and delivering endogenous opioids to the LES muscles is

> > broken.

> >

> > The study hypothesized the effect was not to due to denervation, and

> > that the receptors responsible may be in the LES or other locations.

> >

>

> What the study actually said was, " This finding is unlikely to be the

> result of a denervation process involving opioid nerves. " That does not

> say it was not the result of denervation. They say in the paper that one

> possible explanation " is impairment of non-opioid nerves located between

> the opioid receptor and the lower oesophageal sphincter muscle, ... " and

> another is an " abnormal compensatory neural mechanisms... . "

>

> > The concept of tolerance wasn't addressed. For pain, once a

> > therapeutic dose is achieved the response is long-lasting. ...

> >

>

> Long-lasting effect. (Look below before responding).

>

> > The key main side effects of opioids on the GI tract are nausea and

> > constipation, both of which dissipate with time.

>

> Effects dissipates with time.

>

> So, the effect on pain remains but the effect on those GI symptoms

> dissipates. The LES is part of the GI system. What would be your guess

> for the LES effect? I think more studies are needed. Now, if other

> options were not working I would take this study as hope that some

> opioid treatment could work if I needed it, but I don't think that it is

> enough to overcome popular resistance to the idea.

>

> > Yes, we need more long-term studies. And I encourage the National

> > Institute of Health to conduct more in this field that is wrought with

> > personal prejudice and scientific irrationality. In terms of their

> > use, however, opioids used in methadone maintenance have a documented

> > track record of safety and efficacy, along with providing remarkable

> > functional improvements.

> >

>

> I also wish they would promote more studies on cannabinoid drugs. The GI

> system has cannabinoid receptors and there are many cannabinoid

> substances. Not all of them are mind altering. Seems like there is

> potential there but it is politically unpopular.

>

> >

> > There isn't a guarantee any treatment will work the same for

> > everyyone. But currently, GI will pursue the same approaches for

> > achalasia, and dictate what the results should be - not necessarily

> > from the patients' perspectives. So, mechanically manipulating the LES

> > may be an outsider's basic method of addressing achalasia, but it

> > doesn't even begin to treat all the other symptoms, such as appetite,

> > NCCP, spasms, anxiety, etc.

> >

>

> SOME, GI will pursue the same approaches for achalasia. Probably most,

> but there do exist some that are willing to work with patients who don't

> want to fallow the dilatation/myotomy path. There are members of this

> support group that have chosen not to go that route and have doctors

> working with them. I went six years after being told I should have a

> myotomy before I did. My doctors were happy to let me take that waiting

> option, even the surgeon, who I didn't see until the sixth year and she

> didn't care if I continued to wait. I can't say they would have been as

> willing for others in other situations but they thought it was in my

> case my choice. As doctors are often accused of pushing drugs I can't

> imagine that if I had asked for a pharmacological treatment that they

> wouldn't have offered something and worked with me to find what worked

> for me.

>

> > Many people here are looking for options after having their concerns

> > dismissed by doctors or being pushed into treatments that offer little

> > benefit.

> >

>

> As with many things, one needs to shop to get the best option. That may

> include shopping for a doctor.

>

> > I'm addressing the opioid hypersensitivity to achalasia patients, not

> > " healthy " people.

> >

>

> I don't think it is that black and white. Some of us are more " healthy "

> l than others so millage may vary.

>

> > It should be noted that the administration of naloxone, a strong

> > opioid atagonist, immediately increased LES pressure in the achalasia

> > patients, suggesting a mechanism unique to this group.

> >

>

> " Naloxone had no effect on resting lower oesophageal sphincter pressure

> or swallow induced relaxation in either healthy subjects or achalasia

> patients. " But, it reversed the effect of morphine on the LES.

>

> > > Opiate-induced oesophageal dysmotility.

> > > http://www.ncbi.nlm.nih.gov/pubmed/20003176

> > >

> > > A Patient With Dysphagia Associated With Opioid Medication

> > > http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325310

> >

> > A study with one patient?

> >

>

> It does say that right in the title and that would mean it had just 9

> less achalasia subjects than the study you gave us. But to the point

> that opiates cause problems swallowing in normal patients, such as

> failed LES relaxations, we have 10 from your study (failed relaxations),

> 15 from the first study and 1 from the last for a total of 26. Not a lot

> but we started with just 10 from your study. There may be better studies

> out there, these were easy to find. If this is typical then more studies

> are needed to show otherwise before one can say there is not a problem.

>

> > ... All the decades of methadone maintenance have yet to elucidate any

> > such significant health or cognitive problems.

> >

>

> One drug in a special application not related to people who have

> achalasia. Granted, not much is studied for problems in patients with

> achalasia. Which means this all goes to making an educated guess. Which

> to me seems to be what achalasia and treatments are about. However,

> there are more statics related to achalasia for dilatation and myotomy

> than there are for opiates. There may be more statistics for opiates in

> healthy people than for standard achalasia treatments, but how well do

> they apply to achalasia is also a guess. Take the opiate data and make a

> guess. It will be your guess and not everyone has to guess the same.

> Which is why they practice medicine and not even doctors agree on all

> things.

>

> notan

>

>

>

>