>> Okay. We've almost made
it to the end of the day, so sorry if I bore you. Hopefully I don't. [Laughs] I'm going
to be talking today in this last talk
about "Acupuncture". And for me it's been a really
nice journey to be in this field for the last 25 years, and sort
of see how things have changed and how the pendulum has
kind of swung back and forth. As Dan talked about in the
beginning like fibromyalgia in the early days wasn't even
considered a real condition. And so acupuncture also
has gone through a period where it's been discredited
and there's been a lot of controversy around it. And there's been a lot of people who don't understand
what acupuncture is, and what the research actually
has shown about acupuncture. And hopefully, what I present to you today might
be some information that you may not
normally experience or have been experienced
getting exposure to. So when we talk about
acupuncture, we're actually talking
about a component from traditional
Chinese medicine. And there's a lot
of different things that are considered
alternative or complementary. But the term nowadays
is called "integrative". So we call these therapies
"integrative interventions". And so acupuncture is part
of the mind body class of products interventions. And how often are we
using these things? So this is a survey
that's kind of old, but there's not really
a more recent one. This was one that
was done in 2007. And you can see that
there's a lot of different mind/body
therapies. There's prayer, there's
meditation, there's massage. And actually, acupuncture
here is very low utilized. There's not very many
people that have gone to use acupuncture in 2007. But still it's estimated that about four billion dollars
have been spent that year in out-of-pocket
expenses for this. So this is not something
that you typically go to your primary care
physician and say, "Hey, I'd like to try acupuncture." They may not even know
where to send you, where to go to get acupuncture. So a lot of what -- it's surprising to me that
acupuncture has still been around over the years, because
many of these people are paying for this out-of-pocket rather
than getting reimbursed. So what is acupuncture? Has anyone had an acupuncture
treatment in the audience? All right; wow there's
quite a few of us. Okay, so that's good. So you can see the
acupuncture needles there. You've got a handle and a needle that gets inserted
into the skin. So these needles are not
like a blood-drawing needle like a hypodermic-type
needle to draw blood. They're solid, they're
not hollow. They're designed to not
puncture veins or arteries, so you get very little
bleeding with this. And many times, you don't even
experience the needle getting inserted into the body at all. So many times, the
experience can be actually quite comforting. And so acupuncture is a part
-- it's not the whole thing, it's a part of traditional
Chinese and East Asian medicine. And so it includes
things like Tai chi. So we heard others today talk about how exercise
is very important, and getting the body moving and getting motion is
a very important thing. And so Tai chi is a
component of Asian medicine; and so that's a movement
exercise. There's [inaudible],
which involves massage. And so then there's
also acupuncture, which is a component which may
be part of the intervention that you would get exposed to. So with acupuncture, there's
typically manipulation of the needle. Once it's inserted, it might
be a manual manipulation. There might be thermal
manipulation where they put an herb
called "moxa" on the needle and light it, and
that will give heat that then gets penetrated
into the body. There might be electrical
acupuncture where they run electric
current through the needles. And there's also
chemical acupuncture where there's an injection of
herbal substances into the body, which isn't done in the US, but is very commonly
prescribed in Korea. So there are different
theories behind acupuncture. And each time acupuncture
has been introduced into a culture, it's
been changed. So acupuncture in China
is different from Korea, is different from the
acupuncture that you will find in Japan, and also in
Europe and in France. But typically, it involves
this concept of meridians and channels where the substance
called "chi" is thought to flow. And chi doesn't really
translate very well into the Western language,
but chi is basically in essence you can
think of it as an energy or a function of the body. If you're functioning
well, if you've got energy, if you're vital,
then you're thought to have good chi
and good health. So you may not believe that
and that's quite all right if you don't, but let's just
see what the research kind of shows behind acupuncture,
and what it has shown us. So here I'm plotting
a paper that came out in [inaudible]
a couple years ago, which I think is
quite interesting. So it's plotting the number
of publications in acupuncture over the last 20 years. And what you can see in the black circles are
acupuncture research. So you can see that
over the last 20 years, the number of acupuncture
research articles has increased almost four and a
half fold from 1995. And then as you can see in the
triangles on the lower part -- the triangles on
the low slope there, those are actually just
biomedical articles. So you can see the number of acupuncture research studies
has increased dramatically and has outpaced actually the
amount of research studies that have been done
in more biomedicine, more generic biomedical
literature. Interestingly, before the 1970s,
there were no research articles on acupuncture really
to be thought of; and it actually happened that
when Richard Nixon went to China and gave some lectures there, one of his news staff
members had a case of appendicitis while
he was in China. And they actually did
an appendectomy on him, and used acupuncture as
the analgesic for him. And he had such a nice response
that he wrote an article when he got back to
the United States, and that just basically set off
this trajectory of increasing in acupuncture research. So now I'm going to go
through to what I think is more of the definitive clinical
trials that actually show that acupuncture is
effective for chronic pain. And these trials are part of this acupuncture trialist
collaborative, which is a group of many researchers throughout
the world that have decided to pool the clinical
research data from protocols that were standardized and
generalized across the sites. And so this acupuncture trial's
collaborative was basically designed to answer
two questions, each of the two primary
questions. One of them was, you know, "Is acupuncture better
than standard care? Is it better than usual
care that people are getting for their chronic pain?" This is a very real-world
situation. A patient may come to the
practitioner and says, "Am I going to benefit
from this?" So that's question one. Question two is more
of a methodological or mechanistic kind of research
question and that's asking, "Is acupuncture better
than sham treatment? So that's like is acupuncture
better than a placebo control?" So why I think these studies
are most definitive is because of the numbers
of patients that were in this trial. So they combined data from
over 29 clinical studies; 17,922 patients. So this is very,
very well-powered. Over 20 of the trials had
sham controls, so that's going to answer research question two; there was about 5,000
patients in those studies. And 18 of the trials involved
the non-acupuncture control, so that's like the usual
care or waitlist control. And those studies had over
14,000 patients in them, so very well-powered studies. So the types of non-acupuncture
controls that were used were variable. So some of them involved
no additional intervention, some involved wait listing, some
involved an intention control, like an education, for example;
or it involved usual care that the patients
might be experiencing. And so this next slide I'm
going to show is a forest plot of the facts of acupuncture,
versus usual care or no acupuncture controls
for low back and neck pain. And I don't know if you know
what this type of a plot shows, but it's called a "forest plot". And the vertical
line that's centered around the zero delineates
whether the study favored the control, or whether it
favored acupuncture. And what you can see on the
rows are individual studies. And the dot in the
middle is the mean value. And then the whiskers
represent the precision around that mean value. And so if the whiskers cross
the vertical zero line, then that study sort of failed
to show a significant difference between the control
intervention, which in our case is usual
care, or versus acupuncture. And so as you can
see on the study, many of these trials are shifted
to the right, and that means that they're favoring
acupuncture versus usual care or no acupuncture controls; so that's for low back
pain and neck pain. Here's the same thing
for osteoarthritis pain, again showing a favorable
response to acupuncture versus no acupuncture control. And here's headache
and migraine, again showing a favorable
response to acupuncture versus
the control. So this is a summary
of those slides. And it lists the effect
size and the P value. And I think the P value
is very impressive. All these studies have a
P value of less than .01. But what I think is really
remarkable is the effect size there is .4 to .57. So in the terms of a
clinically meaningful effect, that's a moderate effect size,
which is very, very respectable for this intervention. So that sort of says that
acupuncture is effective, that it's useful when you
compare it to no treatment or usual care, which is I
think the actual situation that most patients are in,
they don't really care so much about whether acupuncture is
different from a placebo or not; they're more interested
in getting relief. And so this data, I think,
is fuel for that argument. But for those of you
that are interested in placebo controlled studies, what does the clinical
trial's results suggest about placebo controls? So you may be wondering, "How
do you control for acupuncture? What is a placebo
for acupuncture?" And it turns out there's no
gold standard placebo control that we actually
have in our hands. There are a number of
different ways that you can go about fooling someone
into thinking that they've got an
acupuncture treatment. One of the more common ways is
using a non-penetrating needle. And so what you can see
there is the person's hand with a Band-Aid on it. And they would insert the
needle into the Band-Aid. And the needle is
actually blunt, so it doesn't actually
penetrate the skin. But when you press down,
the needle retracts into the handle just like
a stage dagger retracts when you get stabbed
with a stage dagger. So it looks like the
needle is going in, but it really isn't
penetrating the skin at all. So that's called the
"[inaudible] needle", because he's the
one who invented it. And that's a very commonly
used sham treatment. There's also studies where
you just prick the skin to make them feel like
they've got needle inserted, and they've been blindfolded so
they can't see what's going on. So there's a number
of different ways that you can control
for placebo effects. So let's see what the
clinical trials look like now. So these are the
same conditions. This is low back pain
and neck pain again. And so in these studies, again
you can see the preponderance for all of these
clinical trials. The mean effect, or the
dot, is shifted to the right of the vertical line at zero, showing that it's
favoring acupuncture. That's for low back pain. This is for osteoarthritis
of the knee. So again, some of the
studies are crossing zero, which means they're not
showing a difference between acupuncture and control. But you can see that
the preponderance of the data is shifted to
the right for osteoarthritis. And then you can also
see that again also with headache and migraine. So this is a summary now
looking at the same conditions. We haven't changed the active
ingredient in our active group, it's still acupuncture; we've
only changed the control group, which was the placebo control. And here you can see the
effect sizes are much smaller. They're on the smallest
range from .15 to .23; but they still are
statistically significant. So the critics in the
acupuncture field -- and there are many,
many critics out there, say that this is just not a
clinically meaningful effect, that this effect size
isn't worth studying and it isn't worth
offering for patients. But I would argue that the
placebo-controlled study isn't necessarily the real-world
setting that the patient experiences. I don't think when the
patient goes to the doctor that the patient says, "Give
me something that's not sham acupuncture," they
just want pain relief. And I think that's something
that's kind of overlooked. So the conclusions from
these clinical trials is that acupuncture is
effective for chronic pain, and it has a moderate
effect size. And the effect of the needling
is statistically significant; it's smaller than effect size. But it suggests that there are
factors other than the needling, then, that are key
at reducing pain. It's not just the
needling that's involved in the pain reduction, it has
an effect, but it's not quite as large as the effect of the
nonspecific contextual factors that go around the intervention. So now I'd like to go into
some studies which might -- one study which might show why
you might need so many people to show a difference
between [inaudible] or real acupuncture
and sham acupuncture. And this is a study which
we did in 2003, which showed that fibromyalgia patients
are not all identical. So even though individuals that
get a label of chronic pain and get a diagnosis of like knee
osteoarthritis or fibromyalgia, they're not all homogeneous. There's actually quite a
lot of variability even within the clinical diagnosis. Like what we've been talking
about today is conditions like fibromyalgia is just
the tip of the iceberg. Many osteoarthritis of the knee
patients have conditions going on within themselves that are
indicative of centralized pain and fibromyalgia pain. And so in this study, we show that there were three different
types of fibromyalgia patients, and some of them could be -- you could categorize them
as conditions of anxiety and depression, as
well as QST measures, which is this MRS
score on the right. You can find type one
individuals have very less -- very low amounts of tenderness, whereas type three individuals
have quite high amounts of tenderness. And so that sort of behooves
us to ask the question about, "Should we actually
design the treatment to best target the
pathology in the patient?" And so this is an article
that came out in 2001 by the late Mitchell
Max and Clifford Woolf. And they were some of
the first individuals to really suggest that, "If we could actually more
accurately pinpoint the pathology of the patient,
we might be more able to design a treatment
to target them." And so we wanted to do
that with acupuncture. And so these are results from
the acupuncture clinical trial that Dan talked about. This is the third acupuncture
study that was funded by NIH to look at the treatment of
acupuncture for fibromyalgia. And here we've just reanalyzed
the data in a way to look to see if there was a difference
in responsiveness to the treatment based
on the sensitivity of the individual person. And so what I'm plotting
here is the sham group is on the upper left
and the [inaudible] or acupuncture group -- two
acupunctures on the upper right. And what I'm plotting on the
Y axis is their clinical pain response to acupuncture, which is increasing treatments
go along on the right. And you can see that
interestingly in the sham group, as they get more sensitive
to needling sensations, they get a very dramatic
increase in their pain reduction; so they
get a very dramatic decrease in their pain. Now, look at the real
acupuncture group in the same scale. They actually show a very
remarkably different phenotype, even it looks like in
the [inaudible] group as they get more
sensitive to the needling, they actually get worse
with the acupuncture. And that's something that many
therapists will sell to you, that if you treat an
acupuncture patient and they have fibromyalgia,
you're not going to stimulate the needle very
strongly, you're not going to get a really strong sensation because they actually
don't like it so much. And so if you look
at the rest of -- the whole rest of the continuum, you can see there's
a dramatic difference between whether someone responds
to sham acupuncture treatment versus real acupuncture
treatment, based on how tender
they are to the thumb, as well as how sensitive
they are to needling. And to bring this home, that means that if you
target the right patient with the right treatment, it
might require less individuals. So for the acupuncture
trialist collaborative that required 1,900 to even
7,000 people in your trial to power a statistically
significant difference between [inaudible]
or real acupuncture and sham acupuncture. But if we limited
this to the patients who had high pressure pain
thresholds, we'd only need 280 to show a difference between
real and sham acupuncture. So actually, I think
there's a lot more that we don't understand
about this intervention. And as the research progresses, I think we're getting a
more clear understanding about who's more
likely to benefit from this treatment
and who's not. I'd like to segue now into
some more mechanistic studies, which I think are
important for chronic pain. There have been a number
of trials that have looked in the brain to see
how acupuncture affects brain activity. And this is a meta-analysis
of 34 fMRI studies, and they've shown
that yes indeed, acupuncture needling can
increase brain activity, specifically in the insula, the mid-singular
cortex, and the thalamus. And these are areas which sham
acupuncture doesn't always get. Look at sham acupuncture
of the blue regions and the green is the overlap. So you can see that there
are some areas of the brain which show similar activations
with the sham treatment as the [inaudible], but there
are definitely some areas which are showing differences between real and
sham acupuncture. We did a study here at
the University of Michigan that showed that acupuncture
was quite effective at changing brain
opioid receptor binding. And I think this is important
given the recent climate of the opioid epidemic
that we're having. And there are many
that have proposed that acupuncture might
be an effective tool to help reduce the craving
in people who are addicted to opioids, and maybe reduce
the long-term dependence on opioids as well. I'd like to highlight
another study by my colleague, Vitaly Napadow in chronic
carpal tunnel pain patients. He did a study where he gave
carpal tunnel patients -- local acupuncture was in one
group, so acupuncture designed of the wrist where
the carpal tunnel is; and then another group
got distal acupuncture, which you may not be aware
of, but there's a theory that if you have the
pain, say, in your wrist, if you treat the ankle
on the opposite side, that might be effective
at helping. Very counterintuitive, but
it actually has been borne out in research that
that might be effective. And then the third group
got sham acupuncture. And what was remarkable in
Vitaly's study was he found that both the local acupuncture
treatment affected brain structural connectivity in
the area of the sensory cortex around the wrist with
local acupuncture. He found that acupuncture in the ankle distally affected
connectivity in local structures in the S1 leg area, but
that then had an effect on carpal tunnel
pathology in the wrist even. So that's really remarkable. And it suggests that local and distal acupuncture might
have differing effects on pain in the wrist, where local
acupuncture effects S1 or sensory cortex area in the
wrist, which then is involved in healing of pain in the wrist, whereas the distal acupuncture
works via another mechanism. So I like this slide
here, it's kind of funny. "You've got to be kidding,
your back still hurts?" [Laughter] So you have
stuck needles everywhere. So it may not be
too critical exactly where the needles are placed,
but I think it is very important to have skin penetration,
and I think it has an effect. But has this really changed
the way healthcare is given? Has this research
actually ever, you know, changed the way patients
are treated? So the Acupuncture Trials
Collaborative did a lot of studies in Germany. And actually the German
Healthcare System was funding a lot of these large clinical
trials of acupuncture. And what's interesting is that
actually the studies resulted in a large increase in
the number of treatments that patients were
getting with acupuncture; it increased about 20%. The German Healthcare
System will pay for these treatments now. They will pay for low
back pain; they will pay for knee osteoarthritis. Similar effects were seen in
the UK following these studies. So the United Kingdom's National
Institute for Health and Care and Excellence recommends
now acupuncture for low back pain
and for headache. So that's a nice
response to the research. So what about the
National Institutes -- what about the United States and the National
Institutes of Health? So interestingly, the NIH
has funded a lot of the basic and the clinical
research in acupuncture. And there's a specific
institute, NCCIH, which is funding a
lot of this research. It's unfortunate to know
that the American College of Rheumatology, actually in
2012, their recommendations, which is kind of
remarkable, they say that, "Treatment with acupuncture is
conditionally recommended only when the patient with knee
OA has chronic to moderate to severe pain, and is
unwilling or contraindicated to undergo arthoplasty." So that's kind of dramatic. So I would be shifting a
little bit away from that. I think that acupuncture is
quite effective for knee OA, and is definitely something that I would recommend a
patient to try, at least. And I think it's worth trying
because it's quite safe. And this is something that
can't be said for some of the interventions
that we have. So this is just one study,
which was published in 2004, and very large trial, 97,000
patients, 7,000 physicians, in Germany treating low
back pain, OA, and headache. So these patients received on
the order of eight sessions that exceeded, which
means they got over 760,000 actual
separate treatments. They had about 7,000
mild adverse events. These were involving
needle pains and hematoma, which is very common; and
those very quickly resolve. But of those 760,000 treatments, there were only six
serious adverse events. And the most common
were pneumothorax. There were two that --
two pneumothorax events, which were due to
inappropriate protocol. Most acupuncturists know not to
insert needles into the back -- perpendicular to the back, because then you can
penetrate the lung and cause a pneumothorax. So that's kind of something that you wouldn't
see normally at all. And then the other serious
adverse events were just maybe related to the acupuncture. So I would say that's
pretty good. You know, out of
760,000 treatments, only six were serious
adverse events; and a lot of those could
have been prevented with accurate protocol. So I think acupuncture
has barriers. There's definitely -- increased
access is really needed. How many of you know where to go to get an acupuncture
treatment if you're interested? So some people do. That's great. Not everyone does. And so I would suggest
if you're interested in getting acupuncture,
there's a board, the National Certification
Commission for Acupuncture and Oriental Medicine, NCCAOM,
is a website that you can go to, and you can click on find
an acupuncture who's board certified in your zip code. And I think this is an
intervention that we need to be actually putting
more on the front line. Many times when people
seek out acupuncture, it's after they've
tried everything else; they've tried surgeries, they've
tried all sorts of drugs, they've tried everything. And they're at their wits
end and they're like, "Okay, I'm now going to
try acupuncture." You know, it's amazing that
this therapy is still around, because the acupuncturists
have been treating the dregs, you know, for many, many years. [Laughter] And the
effects can be seen, because it's still around. So in summary, I'd like to say that acupuncture I think is
effective at reducing pain. I think it's more
than simply placebo. I think it alters brain
function and structure, which we've touched
upon a little bit. I hope you understand that
acupuncture is quite safe. Outside of the US,
acupuncture has been fairly well-incorporated into
clinical guidelines. And I do think acupuncture
access is needed, especially in this
post-opioid era of pain control. And I'd like to thank the team. And I'd like to point
out Noah Zucker, who was a medical student at
the University of Michigan here, and he did some of the analysis
of the needling sensitivity and did a very nice oral
presentation at a conference. And I worked with him
for a number of months, and he did very well and I
was very happy to mentor him. And finally, I'll end. There's an acupuncture
research meeting in Vermont in a couple weeks. If anyone is interested
in learning about how acupuncture
is changing and getting more incorporated
into healthcare, that's going to be a topic at the conference. So thank you very
much for listening. [Applause]