Weight loss(The Role of Weight Loss and Calorie Restriction in Pain Management)

      Weight loss(The Role of Weight Loss and     Calorie Restriction in Pain Management)

 

So i am getting to be

talking concerning weight loss and calorie restriction

today in pain management. And simply a bit little bit of a

heads up, we're extremely -- this is often a somewhat new

field in some ways that. I in all probability can raise

more queries than i'll offer you

answers, however I still assume that this is often a really

exciting new space. I even have no conflicts of interest

or business relationships that i want to confide in you. thus in exploring a relationship

between fatness and pain, it is vital to grasp

That there's a reasonably

well-established relationship within the sense that we all know

that people UN agency area unit overweight or rotund area unit a lot of doubtless

to expertise pain. thus typically speaking our

really high-quality surveys of the general public can realize

that maybe concerning one out of 5 individuals report having

chronic pain or persistent pain. the possibilities of you falling

into that cluster go up concerning half-hour if you're overweight, that means that you just have a BMI

between twenty five and thirty. If you have got a BMI of thirty or

above, then the possibilities go up to concerning hr, ANd an odds

ratio of concerning one.6, that is admittedly i feel a

significant enhanced risk.

And once fatness is already

present in a personal UN agency encompasses a pain condition, we have a tendency to see one thing terribly

interesting happen, that is that almost all of the

symptoms tend to urge worse, albeit we are able to trace the origin

of the pain condition to a time once the person wasn't

overweight or rotund. thus in a very nice study of 215

fibromyalgia patients, it had been shown that those

patients UN agency were overweight or rotund had a lot of

higher levels of fatigue, a lot of bigger sleep disruption, however they were additionally

more sensitive to pain on manual touch

of tender points,

Which suggests one thing

a little bit completely different than simply pain, say, in

the knees, or the ankles, or the hips, or the places that

we classically expect to ascertain it, however truly a lot of of this

central sensitization development could also be a part of fatness. within the classic read of

how fatness promotes pain, we actually borrow pretty

heavily, actually, from form of physical

engineering to explain why we have a tendency to

think it's happening. and you may truly hear this

term "mechanical load" plenty to explain why patients

who area unit overweight or rotund area unit news

a lot a lot of pain in areas just like the lower back, the hips,

the knees, and also the ankles. These are, of course,

the bearing joints of the organic structure, and they are

the ones that area unit most taxed by additional weight,

extra fat. however there is one thing i feel

that is missing from this, that is that if

you actually have faith in your clinical expertise

-- and that i am not a practician. I say that terribly overtly. I facilitate nobody. I deem all of you [laughter]

to do that sort of labor. however if you think that concerning your

patients, what I continuously hear is that this extremely does not

describe the development

Of overweight and rotund

people and also the sorts of pain that they expertise. and really, high-quality

data has began to commence to point out USA that that

is definitely not true, that it's confined to those

weight-bearing joints. In fact, people that area unit

overweight and rotund area unit at a lot of bigger risk of getting

migraine; tension-type headache. they are a lot of doubtless to

have abdominal pain with and while not symptoms

that area unit kind of like irritable internal organ syndrome. they are a lot of doubtless to possess

temporomandibular joint disorder, that primarily

presents as pain within the jaw,

In the system of the face. i might contend that those sorts of pains don't seem to be terribly simply

explained by one thing like mechanical load,

and that we want to quite expand our pondering why

these connections would possibly exist. thus let Pine Tree State offer you one

possible different read of why this happens. fat is

not neutral as so much as our immune systems

are involved. fat tends

to pull immune cells, cause them to migrate into the

tissue, particularly monocytes, that area unit the good

chameleons of the system.

Monocytes area unit there once someone is experiencing a

very severe inflammatory event, and they are there

during wound healing. they will strive against each roles in

the system of the body. thus what happens is that in

adipose-derived inflammation, we have a tendency to tend to possess those monocytes

migrate into the fat tissue, then they begin

to take on a lot of of a unhealthy makeup. that's the monocytes

that {we can|we will|we area unit able to} truly pull out of fat are going

to look plenty just like the monocytes that we might realize

in infected wounds. they are terribly proinflammatory;

they're forcing out out cytokines.

And what will happen even is that

those monocytes and different cells that area unit within the fatty

tissue begin to secrete unhealthy

cytokines at a sufficient concentration

to actually begin to vary the remainder of the

immune system, and even perhaps to start out to signal the brain. These area unit just a few basic

points concerning the qualities of the immune cells

in fat. however however is it that these immune

factors would sensitize the central system,

if this is often true? thus this is often the question I

probably get asked the foremost as a result of I typically speak

about inflammation

And the system and

how it relates to the brain. individuals usually say this to Pine Tree State, "How is it that the

immune system and also the cytokines area unit

affecting the brain?" Most folks learned, right, that

there's one thing referred to as the "blood-brain barrier"

that is a barrier and protectant against

peripheral inflammation. which is completely true,

the barrier is there to stay out those nasty

cytokines and signals of illness from the

periphery of the body. however our brain and our

immune system interact in constant duplex

communication.We would not survive

or function very well if our brain didn't

know what was happening in the peripheral immune system. They're constantly talking. So one of the things

that can happen is that if cytokines reach a

sufficient concentration in blood, they can

actually diffuse across the blood-brain

barrier directly into the brain and spinal cord. And that means that you all

of the sudden have [inaudible] and tumor necrosis factor

[inaudible] beta talking to the immune cells

in your brain.

Now, this normally only happens when somebody is

really quite sick. This is something that's mostly

associated with septic shock or something like that. But there's another route

that we know a lot less about, but we've learned more about

in maybe the last ten years. The immune cells

themselves, not the cytokines, those monocytes themselves,

can actually cross over through our vasculature in

the brain and enter our brain and set up residence there. If you label them

in animal models and then stress the animal,

you can subsequently see them

In various parts of the

brain that are associated with anxiety, and

depression, and pain. So that means that those immune

cells that are not supposed to be getting up here

are in fact doing that. They're getting up there

and they're staying there, and they're changing the

characteristics of the brain in a way that could promote

a lot of these symptoms that we think are really nasty. And in case there's any doubt

about this, this is something that I'm really happy

about and proud of -- actually my friend Neil Basu

[assumed spelling] played a major role in this analysis.

But when Neil came here, we

looked at some RA patients, we did an analysis of the levels

of inflammation in the periphery in a group of RA patients, and

we looked at how that seemed to be associated with the brain. And what we see are profound

changes in the function and structure of the brain in an

individual who has high levels of peripheral inflammation. And this is obviously just a

proof of the basic concept, because this is not in obesity. But I think it's very important

to say that evidence is mounting that as those levels of peripheral information

are increasing,

So the brain is responding

in a commensurate way. So in order to address

this question of obesity inflammation, weight

loss calorie restriction, again, like I said before, I have to

really, really take my hat off to the clinicians who are

involved in these projects. And Amy Rothberg is somebody

who's in family medicine here. She has been doing

a fantastic job of running a weight

management program here at the University of Michigan. At this point, several thousand

patients have actually passed through the program. And what it is primarily

designed

To do is give people

an opportunity to lose weight very rapidly, and then actually get additional

support for another 21 months to take a person out to two

years where they have a period of intense weight loss, and

then they get that maintenance and that additional

support with a nutritionist and seeing the clinician

regularly for a long period after that to actually help

them maintain the weight loss, which we know is

critical to success here. The weight loss itself

is induced through a very low-energy diet. That's another way of just

saying you don't eat very much.

You have a very low

level of calorie intake, typically something like six to

eight hundred calories a day. That is enough to keep your

internal organs healthy and not much else. That is enough to

keep you going, and after that it is

essentially a loss. Of course, any energy

you expend above six to eight hundred

calories per day, which most of us do just being, is going to end up

being weight loss. And that occurs for

about 12 weeks. After that, they enter the

maintenance phase of the program Where they'll get to regularly

meet with a nutritionist and try to maintain the loss

that they have achieved. In studies of the larger

numbers of people who have gone through the program, the

results are really, really nice. What you see are all sorts of

different reductions in BMI, blood pressure, cardiovascular

health risk factors, fasting, glucose, risk of diabetes,

et cetera, et cetera. Not only that, but it appears

to be very cost-effective. I say this just in case

anybody is, you know, sort of wondering how

would this actually fits into a clinical setting,

and could you ever argue that this is actually

cost-effective

For your patients. I think the answer is yes; and there's some nice

data to support that. But what we were really

interested in is, "Well, so what happens when

these patients do go through this period

of rapid weight loss? Do they experience some

improvement in pain?" So this is very much

an observational study. And our only entry

criteria was essentially that you were taking part of

the weight management program, and that you indicated that you

had pain in one or more areas of the body using the 19 sites

On the fibromyalgia

survey criteria, which you've all heard

a lot about today. The [inaudible] survey criteria

gives us a chance to look at how widespread

pain is in the body, and it also gives

us a sense of some of those other comorbid symptoms

that are really troublesome for patients like fatigue,

disruption of sleep, cognitive difficulties, and some

of those other symptoms as well. So what we did is we took 123

patients who had it with pain in at least one site and put

them through the program, and we just gave them the

fibromyalgia survey criteria before and after.It was really actually

that simple. Additionally, 31 of

those patients agreed to have a blood draw before

and after, so we were able to do an analysis of

proinflammatory cytokines just in serum, as well as some

anti-inflammatory cytokines like interleukin 10. So this actually shows

you the raw data of BMI as people go through

the program. And this is truncated to really

focus on the intervention phase, those first 12 weeks where

people are losing weight. And what you can see, I think, is just this really nice

downward slope in BMI indicating

That people are in fact losing

a good amount of weight. And if you kind of look

at the individual lines, what you can see is that if

people stay in the program, the vast majority of them

lose quite a bit of weight. And then during the

maintenance phase, they tend to regain a little

bit, but largely maintain. So what happened? If we look at the body map -- and this is a somewhat

complicated figure, but hopefully you can see

some of the dots showing up a little bit clearly here. What we're doing is we're

looking at patients who lost

At least ten percent

of their body weight, versus those who did not. And what the circles indicate

is how many of them at baseline, the bigger the circle, said

they had pain in that body part when they started the study. And then the color tells you

whether or not it got better or got worse after they went

through the weight loss. What we see is that all

throughout the lower limbs, and in the lower back, and

especially in the abdomen, the chest, and also somewhat

even in the jaw and face, people reported pain

improvement, such that they were about 20% less likely to say

that they had pain in any

Of those regions after

they lost ten percent of their body weight. There was no such effect in

those people who did not lose at least ten percent

of their body weight. Additionally -- hopefully

this is going to show up a little better. That's sort of hard to see. Those are raw changes in

their depression scores. On the left where it says,

"Worsen," those are the patients who actually showed a

little bit of worsening of their depressive

symptoms, and then you can see on the other side those

who actually improved

On their depressive symptoms. It's a really strong

preponderance of patients who are involved in the program who showed a really

substantial increase -- or I should say "benefit"

from a depression standpoint after taking part

in the intervention. Additionally, the

vast, vast majority of patients either showed

an improvement in fatigue, or showed no change, with

very few showing worsening of fatigue, suggesting, again, that you're also seeing some

benefit on those other symptoms. And this was all

true when we looked

At the symptom severity score,

which I'm sure Dan talked about this morning and

others, showing the sort of constellation of

symptoms getting better. Very interestingly,

we saw no difference in proinflammatory cytokines after the intervention

was complete. What had changed is that the

anti-inflammatory cytokine, interleukin 10, had gone up

dramatically in the patients after they lost weight. So what you see there

are sort of paired -- each of the bars

represents an individual. The blue shows you what their

IL-10 levels were at baseline.The orange shows you

after the intervention. You can see them

just sort of spiking up patient after patient. Interleukin 10 is going

up in these patients, which we would expect would

broadly control inflammation, and might have a

positive impact on some of those central pathways

that I was talking about. That was true when we normalized

interleukin 10 to levels of C reactive protein

just to see. So it really looks like there's

a positive inflammatory tone change in those patients

after they lose weight. In some secondary analyses, we

saw some interesting things.

Men cared-for truly show a

greater improvement in fatigue than girls did, however girls still

got a pleasant healthy profit in terms of improvement

in depression and pain. It extremely looked as if

patients World Health Organization failed to reach that one-tenth threshold

did not get the maximum amount like the intervention

over the 12-week amount. And curiously, that

improvement wasn't addicted to what proportion a lot of they same

that they we have a tendency tore exercising; that we thought was one amongst

the sort of obvious confounds or potential explanations

for why this was happening; sleep being another one, however we have a tendency to failed to have a decent

objective live of sleep

In this specific study, one thing that we're

following au fait. therefore currently let ME offer you a

little bit a lot of knowledge that -- this has not however been printed

so this can be a touch of sneak peek. What we're staring at here

now is the follow-up study wherever we have a tendency to same, "Okay, we have a tendency to see that there is clearly

some profit for pain. once will it happen? however long will it take before

people begin experiencing Associate in Nursing improvement in pain? And once will we see these

inflammatory changes?" so what we've done is we've

invited folks to require half

In the study, however currently those

who have way more severe pain to start with; and what

we do is we have a tendency to place them thereon terribly low-energy

diet for 3 weeks, then we have a tendency to place them on

a normal diet for per week, then we have a tendency to place them back

on the terribly low-energy diet. What we're doing is variety of

an on-again/off-again ABC's -- or ABAB style to

try to see whether or not or not inflammation

is going down and up, and also the symptoms area unit

going down and up as we're variable

their calorie intake. On the left there, those are

FM survey criteria scores from alittle cluster of individuals

that we're variety of thinking

Of as a pilot study here. And we've divided them up by

those who had extremely high levels of FMness, medium levels of

FMness, and low levels of FMness once they started the

study, to examine what happens over the primary twelve weeks, with a

special stress on week 3. And what you see here that I

think is actually outstanding is that the patients area unit

showing a dramatic improvement extremely quickly. this can be before

major weight loss. Most of those folks have

lost but 5 p.c of their weight, and tons of that weight

loss is water.

And what we're seeing here is

about a halving of FM symptoms. I keep in mind after I initial

showed this to Dan, he said, "We haven't got any medicine

that work that well." That was extremely outstanding

to me. And it's true, we

don't have medicine that in 3 weeks will cut

fibromyalgia symptoms in [*fr1]. what is attention-grabbing,

too, is that it seems that this improvement simply

sort of stops at 3 weeks, then is maintained

throughout the remainder of the amount. As long as they keep partaking

in the diet, and that they appear to still expertise

that profit.

Those that truly meet

fibromyalgia criteria -- those area unit those on the correct, you'll be able to see that they are showing

absolutely dramatic improvement in even simply alittle range of

patients World Health Organization have FM symptoms. therefore this tells United States one thing

that's extremely attention-grabbing. it's like weight loss

per se isn't essentially the full story. In fact, it should be that the

calorie restriction itself is capable of causing

these fast changes in pain process within the body. And it might be through

inflammatory pathways, it might be through

central systema nervosum,

Neurotransmitter

pathways, we're unsure. however this can be consequent

step so we are able to begin to grasp this

phenomenon higher. and at last, a touch bit a lot of

complicated model suggests that we have a tendency to most likely have exaggerated

inflammation as a results of fat that's

affecting each the brain and also the peripheral joints. it is not either/or; we've

inflammation touching either side of the pathway. lastly, it looks

like these common symptoms, those that you simply

probably see in clinic, area unit dramatically

improved by weight loss

And calorie restriction. It's doable that Associate in Nursing

anti-inflammatory activity, instead of pro-inflammatory

activity, is wherever most of the action is going on, why we're seeing this

angalsic profit. and at last, it's like

these changes occur terribly early, such a awfully low-energy

diet by itself could also be one that does not even ought to

necessarily cause weight loss, might be useful

for some patients.