THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

Volume 14, Number 7, 2!, ""# !$1%C!$& ' M(r) A** L+eber,, I*-#
DOI. 1#1!&/(-m#2!#0AR12
T3e 0,(,u4 (*5 Fu,ure o6 A-u"u*-,ure
Me-3(*+4m Re4e(r-
,Abstract(*5 Hele*e M# L(*7e8+*, M#D#7
On November 8C9, 2007, the Society for Acupuncture Research SAR! hoste" an internationa#
conference to mar$ the tenth anniversary of the #an"mar$ N%& 'Nationa# %nstitutes of &ea#th( Consensus
)eve#opment Conference on Acupuncture* +ore than ,00 acupuncture researchers, practitioners,
stu"ents, fun"in- a-ency personne#, an" hea#th po#icy ana#ysts from 20 countries atten"e" the SAR
meetin- he#" at the .niversity of +ary#an" Schoo# of +e"icine, /a#timore, +)* 0his paper summari1es
important invite" #ectures in the area of basic an" trans#ationa# acupuncture research* Specific areas
inc#u"e the scientific assessment of acupuncture points an" meri"ians, the neura# mechanisms of
car"iovascu#ar re-u#ation by acupuncture, mechanisms for e#ectroacupuncture app#ie" to persistent
inf#ammation an" pain, basic an" trans#ationa# research on acupuncture in -yneco#o-ic app#ications, the
app#ication of functiona# neuroima-in- to acupuncture research 2ith specific app#ication to carpa#3tunne#
syn"rome an" fibromya#-ia, an" the association of the connective tissue system to acupuncture research*
%n summary, mechanistic mo"e#s for acupuncture effects that have been investi-ate" e4perimenta##y have
focuse" on the effects of acupuncture nee"#e stimu#ation on the nervous system, musc#es, an" connective
tissue* 0hese mechanistic mo"e#s are not mutua##y e4c#usive* %terative testin-, e4pan"in-, an" perhaps
mer-in- of such mo"e#s 2i## potentia##y #ea" to an incrementa# un"erstan"in- of the effects of manua#
an" e#ectrica# stimu#ation of acupuncture nee"#es that is so#i"#y roote" in physio#o-y*
Introduction
In November 8C9, 2007, the Society for Acupuncture
Research SAR! hoste" an internationa# conference to
mar$the tenth anniversary of the #an"mar$ N%& 'Nationa#
%nstitutes of &ea#th( Consensus )eve#opment Conference
on Acupuncture* 0his paper summari1es important invite"
#ectures from the SAR conference in the area of basic an"
trans#ationa# acupuncture research* 02o companion
manuscripts have been 2ritten in para##e# an" appear in this
section of the issue* One covers c#inica# research 5ar$ et
a#*, 2008, pp* 87,C88,!, an" the other presents overvie2s
of 6ua#itative stu"ies, the impact of the 7997 N%&
consensus conference, an" future "irections in acupuncture
research +ac5herson et a#*, 2008, pp* 888C889!* %n this
paper, in"ivi"ua#s 2ho "e3#ivere" #ectures on basic an"
trans#ationa# acupuncture research an" have provi"e" the
summaries have been #iste" as coauthors*
Ahn "iscusse" the scientific assessment of the
acupuncture point an" meri"ian* 9on-hurst "escribe"
the neura# mechanisms of car"iovascu#ar re-u#ation by
acupuncture* 9ao "iscusse" mechanisms for
e#ectroacupuncture :A! app#ie" to persistent
inf#ammation an" pain* Stener3;ictorin out#ine" basic
an" trans#ationa# research on acupuncture in -yneco#o-ic
app#ications* Napa"o2 "iscusse" ho2 functiona#
ma-netic resonance ima-in- +R%! has been use" to
eva#uate mechanisms of acupuncture action* &arris
focuse" on functiona# neuroima-in- of acupuncture in
fibromya#-ia* <ina##y, 9an-evin "e#ivere" an overvie2
#ecture, tit#e" =>Acupuncture /asic Research? &o2 )o
@e 5ut %t A## 0o
3
2
,
A
8
B
7+artinos Center for /iome"ica# %ma-in-, +assachusetts Cenera# &ospita#, Char#eston, +A, an" &arvar" +e"ica# Schoo#, /oston,
+A*
Osher Research Center, &arvar" +e"ica# Schoo#, /oston, +A*
Susan Samue#i Center for %nte-rative +e"icine, .niversity of Ca#ifornia, %rvine, CA*
Center for %nte-rative +e"icine, .niversity of +ary#an" Schoo# of +e"icine, /a#timore, +)*
%nstitute of Neuroscience an" 5hysio#o-y, )epartment of 5hysio#o-y, .niversity of Cothenbur-, Cothenbur-, S2e"en*
Chronic 5ain an" <ati-ue Research Center, )epartment of Anesthesio#o-y, .niversity of +ichi-an, Ann Arbor, +%*
)epartment of Neuro#o-y, .niversity of ;ermont, /ur#in-ton, ;0*
86
1
NAPADOW ET AL.862
-etherD=E @hi#e this summary "oes not cover every
"eve#opment in basic acupuncture research in the past 70
years, many of the important a"vancements that have #e" to
a better un"erstan"in- of acupuncture mechanisms 2ere
in"ee" covere" by the invite" spea$ers* 0hrou-h continue"
research into the mechanisms subservin- acupuncture=Fs
c#inica# effects, 2e 2i## be ab#e to optimi1e an" app#y
acupuncture to the c#inica# con"itions, 2hich may benefit
most from this ancient therapeutic system*
Scientifc Assessment o t!e
Acu"uncture Point and #eridian
$A!n%
0he anatomica# an" physio#o-ic nature of the acupuncture
pointGmeri"ian remains e#usive* Our #imite" un"erstan"in-,
ho2ever, is not for #ac$ of e4istin- hypotheses* Numerous
physio#o-ic an" anatomica# associations have been propose"
2ithin the #iterature* 0his summary provi"es a brief revie2
of the scientific assessment of the acupuncture point an"
meri"ian* 0he "iscussion is #imite" to reporte" associations
that a! ref#ect common be#ief, b! are sufficient#y specific to
the acupuncture point an" meri"ian, or c! are supporte" by
more than 2 -oo"36ua#ity stu"ies* @ith this critera, the ta#$
focuses on t2o anatomica# associations nervous system an"
connective tissue!, an" three physio#o-ic associations
tri--er point, nuc#ear tracer mi-ration, an" e#ectrica#
properties! are "iscusse"*
7Neura# corre#ates reporte" in the #iterature inc#u"e #ar-e
periphera# nerves,neurovascu#ar bun"#es,2,motor points,77of
appro4imate#y ,C8 cm per minute*72<or areas 2here the tracer
2as inHecte" at nearby contro#s, the mi-ration 2as not
observe"*77Accor"in- to various e4periments, this phenomenon
is not "irect#y attributab#e to veins or #ymphatics a#thou-h the
interpretation of the resu#ts remains controversia#*
7,0he e#ectrica# characteristics of acupuncture points an"
meri"ians are the most 2i"e#y stu"ie" physio#o-ic
association in the #iterature* Acupuncture points have been
reporte" to be #oca# e#ectrica# resistanceGimpe"ance minima
2ith "iameters of appro4imate#y 7CA mm* Acupuncture
meri"ians have been reporte" to have #o2er e#ectrica#
impe"ance an" hi-her capacitance compare" to a"Hacent
contro#s* A systematic revie2 of this #iterature su--ests that
there is insufficient evi"ence to support the e#ectrica#
association, a#thou-h these "ata are su--estive*%nterestin-#y,
a si-nificant proportion of stu"ies on the anatomica# an"
physio#o-ic nature of acupuncture structures have use" #o2
e#ectrica# resistance points as a surro-ate for acupuncture
points*
Our un"erstan"in- of the anatomica# an" physio#o-ic
nature of acupuncture points an" meri"ians remains
insufficient* 0he scientific characteri1ation of these
acupuncture structures is critica# for the proper e4ecution
of a c#inica# tria#=Ithis characteri1ation "etermines the
proper #oca#i1ation of contro#s an" he#ps i"entify the
optima# therapeutic intervention* <urther attention is
nee"e" to a""ress this re#ative#y ne-#ecte" area of
research
*mechanoreceptors,
7
B
9
70
99mfree nerve en"in-s,8
BC87A0here is
evi"ence from a
series of c#inica#
tria#s for re"uction
in myocar"ia#
ischemia in
patients 2ith
coronary "isease
an" there are more
variab#e "ata for
acupuncture=Fs
abi#ity to #o2er
b#oo" pressure
/5!* <or the #ast
"eca"e, scientists
at our #aboratory
have sou-ht to
un"erstan" the
si-na#in- events
an" neurobio#o-ic
actions of
acupuncture=Fs
re-u#ation of the
car"iovascu#ar
system better*
Our initia#
stu"ies,
pub#ishe" in the
#ate 7990s,
in"icate" that
acupuncture 2as
capab#e of
reversin-
"eman"3in"uce"
myocar"ia#
ischemia in a
fe#ine mo"e# of
partia# coronary
#i-ation*78,7B0his
action of
acupuncture
invo#ve" Croup
%%% an" %;
somatic afferents
an" the
en"o-enous
opiate system,
2hich #o2ere"
myocar"ia# o4y-en "eman" by re"ucin- ref#e43in"uce"
increases in /5*77Subse6uent stu"ies "emonstrate" that
both an" 3opioi", but not 3opioi" receptors in the
rostra# ventro#atera# me"u##a r;9+! 2ere invo#ve" in
acupuncture=Fs action in the brainstem*780hese stu"ies,
supporte" by immunohistochemica# confoca#
microscopy,79,20therefore su--est that 3 en"orphin,
en"omorphin, an" en$epha#in, but not "ynorphin, act as
mo"u#atory neuropepti"es in this re-ion "urin-
acupuncture* +ore recent#y, 2e have sho2n that
nociceptin an" -amma aminobutyric aci" CA/A! are
invo#ve" in inhibition of viscera# ref#e43in"uce"
increases in b#oo" pressure fo##o2in- ,0 minutes of #o23
fre6uency :A at 58C5B acupoints, #ocate" over the
me"ian nerve on the forearms*78,27%n our e4perimenta#
mo"e#s, 2e have "emonstrate" that #o23fre6uency 2CA
&1! but not hi-h3fre6uency 20C700 &1! :A effective#y
stimu#ates somatic afferents to provi"e input to re-ions
such as the r;9+ that re-u#ate sympathetic
outf#o2*27C2,Our stu"ies have a#so e4amine" the
concept of point specificity 2ith re-ar" to
acupuncture=Fs abi#ity to #o2er e#evate" /5*.sin- a
positive an" a ne-ative e#ectro"e connecte" to nee"#es at
t2o a"Hacent acu
3an"
neuromuscu#ar attachments*0he stu"ies 2ere performe"
pre"ominant#y in the 7970s an" 7980s an" 2ere -enera##y poor
in 6ua#ity* 0hese stu"ies #ac$e" appropriate contro#s, ha" sma##
samp#e si1es, an" #ac$e" "etai#e" "escriptions of acupoint
#oca#i1ation* Overa##, no macroscopic anatomica# neura#
structure 2as c#ear#y #in$e" 2ith acupuncture points*
0he most recent anatomica# association reporte" in the
#iterature is the intermuscu#arGintramuscu#ar #oose connective
tissue* Accor"in- to recent stu"ies, many acupuncture
meri"ians an" points a#i-n 2ith intermuscu#ar an"
intramuscu#ar tissue*A""itiona##y, the co##a-en 2ithin the #oose
connective tissue may account for the nee"#e3-rasp effect
reporte" at acupuncture points*0he biomechanica# imp#ications
of this association are evo#vin-, a#thou-h the physio#o-ic an"
c#inica# si-nificance are yet unc#ear*
0he ana#o-y bet2een tri--er points an" acupuncture points
became 2i"e#y "iscusse" since +e#1ac$ et a#*=Fs #an"mar$ stu"y
in 7977*0here are a number of simi#arities bet2een the t2o? the
t2o structures have simi#ar #ocationsJ nee"#es are use" at both
points to treat painJ the pain associate" 2ith the #oca# t2itch
response at tri--er points is simi#ar to the de qi sensationJ an" the
referre" pain -enerate" by nee"#in- tri--er points is simi#ar to
the purporte" propa-ate" sensation a#on- the meri"ians*
&o2ever, the acupoints #ocate" at these tri--er points are not
fre6uent#y use" by acupuncturists an" "o not share the same
c#inica# in"ications as the tri--er point therapy*0ri--er points
may represent a subset of acupuncture points=Ispecifica##y, the
ah shi points*
Nuc#ear tracers have been use" to trac$ the traHectory of
acupuncture meri"ians in both humans an" "o-s* %n most
cases, 0c, in the form of so"ium pertechnetate, 2as
inHecte" at #o2 e#ectrica# resistance points to a superficia#
"epth of ,C8 mm* 0he tracer mi-rate" a#on- the course
of meri"ian at a rateNeura& #ec!anisms o
'ardio(ascu&ar )e*u&ation b+
Acu"uncture $Lon*!urst
%
A',P,N'T,)E #E'-ANIS# )ESEA)'- 86.
22points, 2e have "emonstrate" that acupoints 58C5B,
9%70C9%77, 9%AC9%7, an" St,BCSt,7 effective#y #o2er
/5, 2hereas 9%BC9%7 an" C,7CC,9 are ineffective*780he
e4tent of /5 "epression is "epen"ent on the e4tent of
conver-ent input to premotor sympathetic neurons in the
r;9+* Simp#y p#acin- a nee"#e in an effective acupoint
2ithout mechanica# or e#ectrica# stimu#ation "i" not
inf#uence e#evate" /5, su--estin- that either nee"#e
p#acement 2ithout stimu#ation or e#ectrica# stimu#ation of an
inactive acupoint can serve as a"e6uate sham3contro#
interventions,2AC28Carefu##y comparin- 2 &1 e#ectro3 an"
manua# acupuncture sho2e" simi#ar #o2erin- of ref#e4
e#evations in /5 of appro4imate#y A0K 2ith both
interventions* Recent#y, 2e have be-un to i"entify other
re-ions, inc#u"in- the arcuate nuc#eus in the ventra#
hypotha#amus an" the ventro#atera# peria6ue"ucta# -ray
v#5AC! in the mi"brain that constitute parts of a #on-#oop
path2ay activate" "urin- pro#on-e" 70C,0 minutes!
somatic afferent stimu#ation 2ith :A at 58C5B*2BOur "ata
sho2 that the arcuate is an important source of opioi"
pepti"es that are transporte" to other re-ions such as the
r;9+,27,282hereas the v#5AC is a $no2n car"iovascu#ar3
"epressor re-ion* Stimu#ation of the me"ian nerve,
un"er#yin- 58C5B, increases activity in the arcuate, 2hich
throu-h its proHections, provo$es activity in the v#5AC* 0he
v#5AC either "irect#y or in"irect#y provi"es inhibitory input
to the r;9+ to u#timate#y mo"u#ate premotor sympathetic
outf#o2* %mmunohistochemistry an" micro"ia#ysis
combine" 2ith e#ectrophysio#o-y have sho2n that
sympathoe4citatory viscera# ref#e4es stimu#ate premotor
-#utamater-ic neurons in the r;9+ that are mo"u#ate"
"urin- :A throu-h an opioi" mechanism, because the
process is b#oc$e" by microinHection of
na#o4one*29<urthermore, :A at 58C5B fre6uent#y in"uces
pro#on-e" inhibition of r;9+ premotor sympathetic
neurons, #astin- for more than 90 minutes*790his pro#on-e"
neuromo"u#ation "epen"s on an intact arcuate nuc#eus, an"
both opioi"s an" CA/A, but not nociceptin, systems in the
r;9+*,0Severa# of our stu"ies have sho2n that acupuncture
"oes not re"uce /5 in normotensive human subHects or
e4perimenta# preparations*,7&o2ever, in a""ition to
acupuncture=Fs /53#o2erin- effects, recent intri-uin-
pre#iminary stu"ies su--est that acupuncture a#so may be
ab#e to raise /5 after it has been #o2ere" ref#e4#y*0hus, 2e
are be-innin- to un"erstan" the centra# neurocircuitry an"
neurotransmitter mechanisms un"er#yin- acupuncture=Fs
abi#ity to #o2er /5 in hypertensive states* 0hese stu"ies
may have c#inica# uti#ity for treatin- patients 2ith
hypertension, myocar"ia# ischemia, an" perhaps even
con-estive heart fai#ure=I a## of 2hich are associate" 2ith
hei-htene" sympathetic tone* <uture stu"ies 2i## be "irecte"
at i"entifyin- sti## other re-ions in the brainstem, such as the
me"u##ary raphe nuc#ei, particu#ar#y the nuc#eus raphe
obscurus, in a""ition to the nuc#eus tractus so#itarii, the
nuc#eus ambi-uus an" the "orsa# motor nuc#eus of the
va-us, as 2e## as the many interactions amon- these nuc#ei
that, to-ether, mo"u#ate autonomic outf#o2 an", hence,
car"iovascu#ar function "urin- acupuncture*
E&ectroacu"uncture #ec!anisms on
Persistent In/ammation and Pain
$Lao%
Chronic or persistent inf#ammatory pain anima# mo"e#s,
pro"uce" by inf#ammatory a-ents such as carra-eenan an"
comp#ete <reun"=Fs a"Huvant C<A!, in"uce
inf#ammation#astin- for hours or "ays, respective#y, an"
have recent#y been use" to stu"y the mechanisms of :A*
)urin- the past 8 years, scientists in our #aboratory have
been investi-atin- mechanisms of :A antihypera#-esia an"
:A anti3inf#ammation in a C<A3in"uce" persistent
inf#ammatory pain rat mo"e#*
,2,,,%n the behaviora# tests on this anima# mo"e#, 2e
observe" that the effect of :A is parameter3"epen"ant* :A
at 700 &1 has a potent an" short3term inhibitory effect on
hypera#-esia but #itt#e effect on inf#ammation, 2hi#e 70 &1
of :A has a mo"erate an" pro#on-e" antihypera#-esic
effect as 2e## as an anti3inf#ammatory effect*<urthermore,
our stu"ies a#so "emonstrate that the effect of :A on
hypera#-esia an" inf#ammation is me"iate" by t2o "istinct
path2ays*
T3e 3ormo*(l "(,39() :A anti3inf#ammation is
me"iate" by hypotha#amusCpi3
,A,,8tuitaryCa"rena# &5A! a4is activities, as "emonstrate"
by severa# #ines of evi"ence? 7! At the a"rena# #eve#, :A
treatment si-nificant#y e#evate" p#asma corticosterone
#eve#s an" "ecrease" pa2 e"ema compare" to sham :A*
0his antie"ema effect 2as era"icate" in anima#s -iven an
a"rena#ectomy A)L! an" in those pretreate" 2ith a
corticosterone anta-onist R.A8B,but neither treatment
b#oc$e" the antihypera#-esia effect of :A* 2! At the
pituitary #eve#, :A si-nificant#y increase" p#asma
a"renocorticotropic hormone AC0&! #eve#s, 2hi#e the
AC0& receptor anta-onist AC0&772A!b#oc$e" :A
antie"ema but not :A antihypera#-esia unpub#ishe" "ata!*
,! At the hypotha#amus #eve#, a corticotropin3re#easin-
factor CR<! receptor anta-onist, astressin, b#oc$e" :A
antie"ema but on#y partia##y b#oc$e" the effect of :A
antihypera#-esia unpub#ishe" "ata!* @e a#so foun" that :A
"i" not increase p#asma corticosterone COR0! an" AC0&
#eve#s in naive rats, 2hich su--ests that :A affects hea#thy
an" patho#o-ic con"itions "ifferent#y*
T3e *eur(l "(,39() At the spina# #eve#, :A
si-nificant#y inhibite" C<A3in3
,A,,8"uce" Fos e4pression in the spina# "orsa# horn,
particu#ar#y at #aminae %3%%*,B5harmaco#o-ic stu"ies sho2e"
that :A antihypera#-esia is me"iate" by mu an" "e#ta but not
$appa opioi" receptors*,7Stu"ies a#so sho2 that #esionin- of
the C3protein3coup#e" receptor by pertussis to4in b#oc$s :A
antihypera#-esia*,8Specifica##y, #esionin- of mu
receptorCcontainin- spina# neurons 2ith "ermorphin3
saporin sho2s this effect*,9<urthermore, a "orso#atera#
funicu#us #esion in the #o2er thoracic spina# cor"
si-nificant#y "iminishes the effect of :A
antihypera#-esia*,9At the supraspina# #eve#, :A activates Fos
e4pression in the nuc#eus raphe ma-nus an" #ocus
coeru#eus*,9Our immunochemistry "oub#e3stainin- "ata sho2
that :A specifica##y activates serotonin3 or tyrosine
hy"ro4y#aseCcontainin- neurons in these nuc#ei, 2hich
proHect to the spina# cor"*
%n conc#usion, the rat persistent inf#ammatory pain mo"e#
has provi"e" an i"ea# anima# mo"e# for investi-atin- the
effect an" mechanisms of acupuncture on inf#ammatory
pain an" has pro"uce" "ata 2ith potentia# c#inica#
re#evance for the treatment of chronic inf#ammatory pain*
:A antihypera#-esia an" antie"ema are parameter3
"epen"ent an", moreover, are me"iate" via t2o "istinct
path2ays* :A3pro"uce" antihypera#-esia is main#y
me"iate" by sensory nerve path
3
NAPADOW ET AL.860
2ays invo#vin- both spina# an" supraspina# mechanisms,
2hi#e :A3pro"uce" anti3inf#ammatory effects are main#y
me"iate" by activation of the &5A a4is*
Acu"uncture in 1+neco&o*+
$Stener23ictorin% Fem(le
+*6er,+l+,):;b(4+- (*5 -l+*+-(l 4,u5+e4
)espite the #ac$ of a #ar-e bo"y of evi"ence =I2e cannot
i-nore the fact that many 2omen receive acupuncture
treatment to a""ress inferti#ity issues* @hether there is a true
effect 2ithin the area of inferti#ity or not, is a compe##in-
reason for the scientific community to investi-ate*
Acupuncture is a safe intervention in the han"s of competent
practitioners* %n this sense, specia# acupuncture trainin- in
the area of 2omen=Fs hea#th is essentia#*
A0A7,A2Recent basic an" c#inica# research "emonstrate that
acupuncture re-u#ates uterinean" ovarian b#oo" f#o2,
A7that the effect most #i$e#y is me"iate" as a ref#e4 response
via the ovarian sympathetic nerves, an" that the response is
contro##e" via supraspina# path2ays*%t is important to point
out that these stu"ies sho2 that the effect of acupuncture, at
#east partia##y, is me"iate" via sympathetic nerves but she"
no #i-ht on the ro#e of acupuncture in inferti#ity treatment*
A-u"u*-,ure +* e*5o-r+*e (*5 me,(bol+-
5+4or5er4 5o#ycystic ovary syn"rome 5COS! is the most
common
A,en"ocrine an" metabo#ic "isor"er=I=>the fema#e metabo#ic
syn"rome=E=Iassociate" 2ith ovu#atory "ysfunction,
ab"omina# obesity, hyperan"ro-enism, hypertension, an"
insu#in resistance* 0he precise etio#o-y of the "isease is
un$no2n but e4cessive ovarian an"ro-en pro"uction an"
secretion seem to p#ay a $ey ro#e* A potentia# contribution of
the sympathetic nervous system as a primary factor in the
"eve#opment an" maintenance of 5COS has been
su--este"*AA@e have con"ucte" a stu"y on 2omen 2ith
2e##"efine" an" "ia-nose" 5COS an" anovu#ation to
e#uci"ate the effect of repeate" #o23fre6uency 2 &1! :A
treatments on en"ocrino#o-ic an" neuroen"ocrino#o-ic
parameters as 2e## as on anovu#ation*A8,AB0his stu"y sho2e"
that repeate" #o23fre6uency :A treatments e4ert #on-3#astin-
effects on both en"ocrino#o-ic parameters as 2e## as on
anovu#ation* 0hese resu#ts are in accor"ance 2ith previous
stu"ies,
but it is obvious that ran"omi1e", comparative stu"ies are
nee"e" to verify these resu#ts* &o2ever, these stu"ies "o not
en#i-hten possib#e un"er#yin- mechanisms of :A, but it can
be hypothesi1e" that these :A effects are me"iate" throu-h
inhibition of the activity in the ovarian sympathetic nerves*
A7%n recent stu"ies on an estra"io# va#erate :;!Cin"uce"
rat po#ycystic ovary 5CO! mo"e#, 2e sho2e" that repeate"
#o23fre6uency :A treatments resu#te" in a re"uction of hi-h
ovarian nerve -ro2th factor NC<!, corticotrophin3
re#easin- factor, an" en"othe#in37 concentrations=Ia##
mar$ers for sympathetic activity=Ias 2e## as increase" #o2
hypotha#amic b3en"orphin concentrations an" immune
function*@e have teste" the hypothesis further that repeate"
#o23fre6uency :A treatments as 2e## as physica# e4ercise
mo"u#ates sympathetic nerve activity in rats 2ith steroi"3
in"uce" 5CO by stu"yin- the e4pression of mRNA an"
proteins of 3 7a3 7b3 an" N0R7"23a"renoceptors an" the NC<
receptor p78an" immunohistochemica# e4pression of
tyrosinehy"ro4y#ase 0&!*A85hysica# e4ercise a#most
norma#i1e" ovarian morpho#o-y an" both :A an" physica#
e4ercise norma#i1e" the e4pression of NC< an" NC<3
receptors, as 2e## as 73 an" 23AR, su--estin- that these
interventions may have a therapeutic effect*
A,Recent#y, our -roup "eve#ope" a ne2 rat 5COS mo"e# that
incorporates ovarian and metabo#ic characteristics of the
syn"rome*A9After continuous e4posure to 83
"ihy"rotestosterone, from prepuberty unti# a"u#t a-e, the rats
have typica# 5CO 2ith an increase" number of apoptotic
fo##ic#es* +oreover, the rats "eve#op obesity accompanie" by
en#ar-e" a"ipocyte si1e an" insu#in resistance, in"icatin-
that hi-h #eve#s of an"ro-ens in"uce a#terations in bo"y
composition an" re"uce" insu#in sensitivity in this 5COS
mo"e#* @hat is of -reat importance is that 2e have sho2n
that #o23fre6uency :A and e4ercise ame#iorate insu#in
resistance in rats 2ith 5COS*0his effect may invo#ve
re-u#ation of a"iposetissue metabo#ism an" pro"uction
because :A an" e4ercise each partia##y restore "iver-ent
a"ipose3tissue -ene e4pression associate" 2ith insu#in
resistance, obesity, an" inf#ammation* %n contrast to e4ercise,
:A improves insu#in sensitivity an" mo"u#ates a"ipose3
tissue -ene e4pression 2ithout inf#uencin- a"ipose tissue
mass an" ce##u#arity*
A,0hese rat 5COG5COS stu"ies "emonstrate that #o23
fre6uency :A in"uces effects on the en"ocrine, the
metabo#ic, an" the sympathetic nervous system*
A-u"u*-,ure +* -o*<u*-,+o* ,o +* 8+,ro
6er,+l+=(,+o* (*5 embr)o ,r(*46er
80Since the first pub#ications reportin- the use of
acupuncture as an ana#-esic metho" "urin- oocyte retrieva#
in in vitro ferti#i1ation %;<! treatment,87an" #ater stu"ies
investi-atin- the ro#e of acupuncture before, "urin- an" after
embryo transfer :0!,82,8,the c#inica# use of acupuncture has
become 2i"esprea"* 0hese recent stu"ies re-ar"in- the ro#e
of acupuncture in %;<G:0 treatment, focusin- on oocyte
aspiration an" :0, has been -iven much attention in "ebate
an" revie2 papers*8A+any of the tria#s are un"erpo2ere"
an" the stu"y "esi-ns amon- the tria#s "iffer, 2hich ma$es it
har" to interpret the "ata* &o2ever, the authors of a recent
revie2 conc#u"e" that current pre#iminary evi"ence su--ests
that acupuncture -iven before an" after :0 improves rates of
pre-nancy an" #ive births amon- 2omen un"er-oin-
%;<*88%n this conte4t, it is important to emphasi1e that, in a
comment in the British Medical Journal, it is note" that a
)anish ran"omi1e" contro##e" tria# RC0! on a"Huvant
acupuncture that inc#u"es more than B00 2omen havin- %;<
t2ice as many as in the #ar-est RC0 inc#u"e" in the
metaana#ysis! is current#y un"er2ay*/efore a""in- a"Huvant
acupuncture for %;< to any nationa# -ui"e#ine, 2e must 2ait
for the resu#ts of this an" other stu"ies to c#arify the va#ue of
this treatment*
%n conc#usion, it appears that acupuncture may have a
beneficia# effect on 2omen 2ith 5COSJ this possibi#ity is
supporte" by both c#inica# an" e4perimenta# evi"ence*
&o2ever, there is a nee" for more RC0s on 2omen 2ith
2e##3"efine" "ia-noses of 5COS* 0he resu#ts in"icate that
#o23fre6uency :A mo"u#ates sympathetic activity*
<urthermore, acupuncture in conHunction 2ith %;<G:0
treatment mi-ht have a potentia# ro#e but sti## there is a
#ac$ of c#ear evi"ence to support this possibi#ity yet
*
A',P,N'T,)E #E'-ANIS# )ESEA)'- 864
E(a&uatin* Acu"uncture 5it!
6unctiona& #a*netic )esonance
Ima*in*7 6rom '!aracteri8ation to
Trans&ationa& )esearc! $Na"ado5%
8BA#thou-h anima# research c#ear#y supports a ro#e for
antinociceptive #imbic, hypotha#amic, an" brainstem
net2or$s in acupuncture ana#-esia, these resu#ts must be
p#ace" in the conte4t of more comp#e4 human co-nition*
One comp#ementary approach to stu"y neurophysio#o-ic
corre#ates of acupuncture in humans inc#u"es
neuroima-in-=Imappin- or #oca#i1in- brain function*A
#ea"in- noninvasive neuroima-in- metho" 2ith -oo" spatia#
an" a"e6uate tempora# reso#ution is the hemo"ynamic3base"
functiona# +R% f+R%!, 2hich can estimate activity
any2here in the brain every fe2 secon"s* 0he use of f+R%
to stu"y acupuncture has occurre" since the mi"37990s an"
has inc#u"e" both characteri1ation stu"ies in 2hich nee"#e
stimu#ation 2as performe" "urin- neuroima-in-, as 2e## as
stu"ies in 2hich brain responses to conventiona#, 2e##3
characteri1e" stimu#i 2ere eva#uate" both before an" after
acupuncture*
87CB0Characteri1ation stu"ies from severa# -roups have
"emonstrate" over#appin- responses to acupuncture 2ithin
mu#tip#e cortica#, subcortica#G#imbic, an" brainstem areas*
B70his shou#" not be surprisin- as acupuncture is a comp#e4
somatosensory stimu#us that is sure to e#icit sensorimotor,
affective an" hi-her co-nitiveGeva#uative processin-*
Re-ions inc#u"e the primary an" secon"ary somatosensory
cortices S%, S%%!, 2hich support initia# #oca#i1ation an" ear#y
6ua#itative characteri1ation of somatosensory stimu#i*
9imbic brain re-ions e*-*, the hypotha#amus, amy-"a#a,
anterior cin-u#ate corte4 'ACC(, an" hippocampus! are a#so
recruite", an" probab#y me"iate any affectiveGemotiona#
response* <urthermore, many characteri1ation stu"ies have
"emonstrate" mo"u#ation of the anterior an" posterior
insu#a, an" the prefronta# corte4 5<C!* 0he insu#a have been
imp#icate" in pain processin- an" may p#ay a specific ro#e
for acupuncture,B22hi#e the 5<C has mu#tip#e "istribute"
connections 2ith the #imbic system an" is #i$e#y to a#so p#ay
an important ro#e in e4pectancy3re#ate" responses*
B,Stu"ies usin- f+R% have a#so investi-ate" ho2
acupuncture mo"u#ates 2e##3characteri1e" pain stimu#i,
nonpain somatosensation, an" even restin- brain function*
<or instance, 2e recent#y foun" that fo##o2in- verum, but
not sham, acupuncture, there 2as increase" restin-
functiona# connectivity bet2een specific brain areas an" the
"efau#t mo"e net2or$ )+N!=Ia net2or$ of brain re-ions
more active "urin- a nontas$ processin- state, an" thou-ht
to subserve interoception or se#f3referentia#
co-nition*Specifica##y, postacupuncture, the )+N 2as more
connecte" 2ith painACC, peria6ue"ucta# -ray '5AC(!,
affective3 amy-"a#a, ACC!, an" memory3 hippocampa#
formation, mi""#e tempora# -yrus! re#ate" brain re-ions*
0hese resu#ts "emonstrate that acupuncture "oes not Hust
affect brain function during nee"#e stimu#ation but can
enhance the poststimu#ation spatia# e4tent of restin- brain
net2or$s* 0his effect may p#ay a ro#e in acupuncture
ana#-esia, 2hich is $no2n to "eve#op after si-nificant time
"e#ays*
BANeuroima-in- can a#so be coup#e" 2ith #on-itu"ina#
c#inica# eva#uation, as 2e have "one for carpa# tunne#
syn"rome C0S!* After a 832ee$ course of acupuncture,
patients 2ith C0S ha" #ess hyperactivation to fin-er
stimu#ation, an" more focuse" S% fin-er
representation*<urthermore, 2e foun"B8that, compare" to
hea#thy a"u#ts, patients 2ith C0S ha" more c#ose#y separate"
somatotopic representations for the secon" an" thir" fin-ers
both me"ian3nerve innervate"!*
BBAfter acupuncture treatment, the secon" an" thir" fin-er
representations 2ere further apart, appro4imatin- the
separation seen in hea#thy a"u#ts* <urthermore, 2e foun"
that, compare" to hea#thy contro#s, patients 2ith C0S
respon"e" to acupuncture at 9%3A, "ista# to the #esion! 2ith
-reater hypotha#amic activation an" more preva#ent
amy-"a#a "eactivation*
%n the future, characteri1ation stu"ies 2i## continue to be
important especia##y in corre#ation 2ith periphera# an"
c#inica# metrics!, as 2e sti## "o not $no2 the =>specific
effect=E of acupuncture* &o2ever, ne2er approaches to
f+R% e*-*, functiona# connectivity! coup#e" 2ith c#inica#
eva#uation 2i## become more prominent in the comin- years
as 2e try to un"erstan" the mechanisms behin" some of the
ambi-uous resu#ts acup sham! from recent RC0s*
6unctiona& Neuroima*in* o
Acu"uncture in 6ibrom+a&*ia7
Insi*!ts into #ec!anisms and
'&inica& Tria& Desi*n $-arris%
B7<ibromya#-ia <+! is a common chronic pain con"ition
that aff#icts appro4imate#y 2KCAK of in"ivi"ua#s in
in"ustria#i1e" countries*B8,B9A#thou-h the un"er#yin-
patho#o-y of this con"ition is un$no2n, a "isturbance in
centra# neura# function has been su--este"* Research usin-
f+R% has sho2n that brain re-ions $no2n to process an"
mo"u#ate pain information have au-mente" activity in these
patients*70+ore recent#y, positron emission tomo-raphy
5:0!, a brain3ima-in- techni6ue that can be use" to assess
static an" "ynamic aspects of neurotransmitter systems, has
been use" to stu"y 3opioi" receptor +OR!Cbin"in- abi#ity
in <+*+ORs 2ithin the nuc#eus accumbens, the cin-u#ate,
an" the amy-"a#a sho2 re"uce" bin"in- abi#ity in patients
2ith <+* /ecause these receptors norma##y function to
inhibit neura# activity, these patients may have re"uce"
inhibitory neurotransmission in pain3mo"u#atin- brain
re-ions*
77C7,Severa# c#inica# tria#s of acupuncture in <+ have been
performe" to "ateJ ho2ever, the fin"in-s have been
e6uivoca#, 2ith most stu"ies sho2in- that acupuncture an"
sham acupuncture SA! are e6ua##y effective for re"ucin-
pain*
7A,78As a conse6uence, the acupuncture fie#" has ha" troub#e
separatin- acupuncture ana#-esic effects from p#acebo
effects in <+* Neuroima-in- metho"s such as 5:0 may
provi"e insi-hts into this prob#em* /ecause +ORs have
been imp#icate" in both acupuncture as 2e## as p#acebo
ana#-esia,
functiona# ima-in- of these receptors may provi"e
information into acupuncture effects*
@e uti#i1e" 5:0 ima-in- to fin" out 2hether acupuncture
an" SA 2ou#" have the same effects on centra# opioi"
receptors in patients 2ith <+* Seventeen 77! patients 2ith
<+ 2ere ran"omi1e" to receive either 9 tra"itiona#
acupuncture 0AJ n 9! or 9 SA n 8! sessions over the
course of 7 month* 5:0 ima-in- an" c#inica# pain ratin-s,
assesse" 2ith the short form of the +cCi## 5ain
Muestionnaire S<+5M!, 2ere performe" pre3 an" post3
treatment*
As e4pecte" there, 2as no "ifference in c#inica# pain
re"uction for both -roups S<+5M tota#? +ean)iff
stan"ar" "eviation! 0A 8*A 9*B!J SA 2*, B*A!J p 0*AA!*
&o2eve
r
NAPADOW ET AL.866
the t2o interventions ha" "ramatica##y "ifferent effects on
centra# +OR bin"in- abi#ity* %n the insu#a, the amy-"a#a, the
tha#amus, the cin-u#ate anterior an" peri-enua#!, the
cau"ate, an" the prefronta# corte4, 0A cause" an increase in
+OR bin"in- abi#ity, 2hereas SA cause" a "ecrease in
receptor bin"in- abi#ity a## p 0*007J uncorrecte"!* 0hese
"ata su--est that, 2hi#e acupuncture an" SA have simi#ar
effects on c#inica# pain, their un"er#yin- opioi"3receptor
mechanisms are not e6uiva#ent*
Resu#ts from neuroima-in- stu"ies such as these have
ha" minima# impact on c#inica# tria#s of acupuncture to
"ate* %f 0A is not simp#y the sum of SA p#us any specific
nee"#in- effects, this fin"in- has imp#ications for the
"esi-n of acupuncture c#inica# tria#s* One may not be ab#e
to assume that the effects of SA are embe""e" in the
active treatment arm in the same 2ay that =>p#acebo
effects=E are thou-ht to operate in the active arm of a
"ru- tria#* Rep#ication an" va#i"ation of these fin"in-s
re6uires further investi-ation*
Acu"uncture 9asic )esearc!7 -o5 Do
We Put It A&& To*et!er: $Lan*e(in%
A#thou-h basic research on acupuncture has ma"e
consi"erab#e pro-ress in the past 70 years, 2e sti## #ac$ a
c#ear picture of =>ho2 acupuncture 2or$s*=E An on-oin-
source of frustration, especia##y amon- practitioners of
acupuncture, is that e4istin- mechanistic mo"e#s have ten"e"
to -reat#y =>simp#ify=E acupuncture* A#thou-h such mo"e#s
may app#y to specific situations e*-*, obtainin- imme"iate
ana#-esic effects!, it is not c#ear ho2 they re#ate to
acupuncture practice as a 2ho#e, 2hich inc#u"es treatment of
comp#e4 chronic con"itions* An a""itiona# source of
confusion is that the term =>acupuncture=E is use" by some
peop#e to "escribe a variety of proce"ures performe" at
acupuncture points but not necessari#y invo#vin- nee"#es
e*-*, =>noninsertive=E metho"s or #aser stimu#ation!, 2hi#e
other peop#e "efine acupuncture is as a proce"ure invo#vin-
the insertion of acupuncture nee"#es, but not necessari#y at
acupuncture points* )espite these "ifficu#ties, mechanistic
mo"e#s are important as they provi"e a frame2or$ to test
specific hypotheses* 0o be optima##y usefu#, mo"e#s nee" to
have a 2e##3"efine" scope an" a so#i" physio#o-ic
foun"ation, an" be testab#e, -iven current#y avai#ab#e
techno#o-y*
So far, mechanistic mo"e#s that have been investi-ate"
e4perimenta##y have focuse" on the effects of
acupuncturenee"#e stimu#ation on the nervous system,
musc#es, an" connective tissue* /y far, the most
e4tensive#y teste" mo"e# has been that of neura#
stimu#ation* @e##3"ocumente" an" repro"ucib#e effects on
the periphera#, centra#, an" autonomic nervous systems
have been "emonstrate" for both manua# an" e#ectrica#
stimu#ation 2ith acupuncture nee"#es in humans an"
anima#s* 0he re#evance of these mechanisms to pain
re"uction, periphera# anti3inf#ammation, car"iovascu#ar,
-astrointestina#, an" en"ocrine re-u#ation are summari1e"
in the prece"in- papers by 9on-hurst, 9ao, Stener3
;ictorin, Napa"o2, an" &arris* Another mo"e# that has
receive" a substantia# amount of attention is the =>tri--er3
point=E musc#e stimu#ation mo"e#* Acupuncture nee"#e
manipu#ation can be use" to stimu#ate hyperirritab#e foci
at neuromuscu#ar Hunctions causin- a specific =>t2itch
response=E that can a#ter e4trace##u#ar
inf#ammatory7Bme"iators surroun"in- the tri--er point,
su--estin- that this mechanism may be re#ate" to #oca# pain
re"uction*77,78<ina##y, the connective3tissue stimu#ation
mo"e# 2as base" on the observation that manua# stimu#ation
2ith acupuncture nee"#es causes hi-h#y specific mechanica#
stimu#ation of subcutaneous #oose connective tissue*
<ibrob#asts 2ithin the #oose connective tissue respon" to this
mechanica# stimu#ation 2ith active cytos$e#eta# remo"e#in-
that may have important "o2nstream effects 2ithin
connective tissue*BA#thou-h the re#ationship bet2een these
connective3tissue responses an" c#inica# effects remains
un$no2n, the intri-uin- over#ap bet2een acupuncture
meri"ians an" connective tissue su--ests a possib#e
re#evance of this connective3tissue mo"e# to poor#y
un"erstoo" 0ra"itiona# Chinese +e"icine concepts, such as
propa-ation of effects a#on- acupuncture meri"ians*%t is of
course important to emphasi1e that these mechanistic
mo"e#s are not mutua##y e4c#usive* %terative testin-,
e4pan"in-, an" perhaps mer-in- of such mo"e#s 2i##
potentia##y #ea" to an incrementa# un"erstan"in- of the
effects of manua# an" e#ectrica# stimu#ation 2ith acupuncture
nee"#es that is so#i"#y roote" in physio#o-y*
Ac;no5&ed*ments 0he Society for Acupuncture
Research SAR! 2007 annua#
conference 2as supporte" in part by a Nationa# Center for
Comp#ementary +e"icine NCCA+!GN%& -rant
R7,A000A7A,!* Contributions by An"re2 Ahn, +*)*,
+*5*&*, 2ere supporte" by the NCCA+ N%&! -rant N2,3
A000,2,8* Contributions by Oohn 9on-hurst, +*)*, 5h*)*,
2ere supporte" in part by N%& R07 &93B,,7,, &9372728,
the 9arry N* )o"-e Chair in %nte-rative /io#o-y, the Susan
Samue#i Chair in %nte-rative +e"icine, an" the 5eterson
<ami#y Cift* Contributions by 9i4in- 9ao, 5h*)*, C*+*)*
China!, 2ere supporte" by N%& -rants 5803A00008A an"
5073A0002B08* Contributions by :#isabet Stener3;ictorin,
5h*)*, 2ere supporte" in part by the S2e"ish Research
Counci# 5roHect No* 200A3B,99 an" 200A3B827!, 9.AGA9<
5roHect No* 7870!, A9<C/C37097A, )iabetic <oun"ation,
Novo Nor"is$, P$e @iber- Research <oun"ation, :$ha-a
<oun"ation, @i#he#m an" +artina 9un"-rens=Fs Science
<un", 0ore Ni#ssons <oun"ation, &Ha#mar Svensson
<oun"ation, an" +a-nus /er-2a##s Stifte#se* Contributions
by ;ita#y Napa"o2, 5h*)*, 9ic*Ac, 2ere supporte" by the
fo##o2in- NCCA+ N%&! -rants? 5073A00020A8, N073
A00027BB* Contributions by Richar" &arris, 5h*)*, 2ere
supporte" by the fo##o2in- -rants? NCCA+ N%&!
A007777307J NCCA+ N%&! R07 A0 007A78J NCRR N%&!
-rant +073RR0000A2J an" the )epartment of the Army
-rant )A+)377G00230078*
)eerences
7* )un-, &C* Acupuncture points of the cervica# p#e4us*
Am Chin +e"798AJ727CA!?9AC708*
2* /ossy O* +orpho#o-ica# "ata concernin- the acupuncture
points an" channe# net2or$* Acupunct :#ectrother Res
798AJ9?79C70B*
,* 9iu Q, ;are#a +, Os2a#" R* 0he correspon"ence bet2een
some motor points an" acupuncture #oci* Am O Chin +e"
7978J,?,A7C,88*
A* Ne##ner C* On a vascu#ari1e" nerve3en"in- corpusc#e of
the Nrause en"3or-an type* R +i$ros$ Anat <orsch 79BBJ78?
7,0C7AA
*
A',P,N'T,)E #E'-ANIS# )ESEA)'- 86<
8* Cis1e$ +, S1opins$i O, S$r1ypu#ec ;* %nvesti-ations of
morpho#o-ica# structure of acupuncture points an"
meri"ians* O 0ra"it Chin +e", 7988J8?289C292*
B* 9an-evin &+, Qan"o2 OA* Re#ationship of acupuncture
points an" meri"ians to connective tissue p#anes* Anat Rec
2002J2B9?287C2B8*
7* 9an-evin &+, Churchi## )9, Cipo##a +O* +echanica#
si-na#in- throu-h connective tissue? A mechanism for the
therapeutic effect of acupuncture* <AS:/ O 2007J78?2278C
2282*
8* 9an-evin &+, Churchi## )9, <o4 OR, et a#*
/iomechanica# response to acupuncture nee"#in- in
humans* O App# 5hysio# 2007J97?2A77C2A78*
9* +e#1ac$ R, Sti##2e## )+, <o4 :O* 0ri--er points an"
acupuncture points for pain? Corre#ations an" imp#ications
'revie2(* 5ain 7977J,?,C2,*
70* /irch S, <e#t /* .n"erstan"in- Acupuncture*
:"inbur-h? Churchi## 9ivin-stone, %nc*, 7999*
77* )arras, O3C, ;erneHou# 5), A#bare"e 5* Nuc#ear
me"icine an" acupuncture? A stu"y on the mi-ration of
ra"ioactive tracers after inHection at acupoints* Am O
Acupunct 7992J 20?2A8C28B*
9972* Novacs <, Cot1ens ;, Carcia A, et a#* :4perimenta#
stu"y on ra"ioactive path2ays of hypo"ermica##y inHecte"
0echnetium3m* O Nuc# +e" 7992J,,?A0,CA07* 7,* Ahn
AC, Co#bert A5, An"erson /O, et a#* :#ectrica# proper3
ties of acupuncture points an" meri"ians? A systematic
revie2* /ioe#ectroma-netics 2008J 29?2A8C28B*
7A* 9i 5, 5itsi##i"es N<, Ren"i- S;, et a#* Reversa# of ref#e43
in"uce" myocar"ia# ischemia by me"ian nerve stimu#ation?
A fe#ine mo"e# of e#ectroacupuncture* Circu#ation 7998J97?
778BC779A*
78* Rhou @, <u 9@, 0Hen3A39ooi SC, et a#* Afferent
mechanisms un"er#yin- stimu#ation mo"a#ity3re#ate"
mo"u#ation of acupuncture3re#ate" car"iovascu#ar
responses* O App# 5hysio# 2008J98?872C880*
7B* Chao )+, Shen 99, 0Hen A9S, et a#* Na#o4one reverses
inhibitory effect of e#ectroacupuncture on sympathetic
car"iovascu#ar ref#e4 responses* Am O 5hysio#
7999J27BB'pt2(!? &2727C&27,A*
77* 9i 5, 0Hen3A39ooi SC, 9on-hurst OC* Rostra#
ventro#atera# me"u##ary opioi" receptor subtypes in the
inhibitory effect of e#ectroacupuncture on ref#e4 autonomic
response in cats* Auton Neurosci 2007J897C2!?,8CA7*
78* Cuo R9, +oa11ami AR, 9on-hurst OC*
:#ectroacupuncture in"uces c-Fos e4pression in the rostra#
ventro#atera# me"u##a an" peria6ue"ucta# -ray in cats?
Re#ation to opioi" containin- neurons* /rain Res
200AJ70,0?70,C778*
79* 0Hen3A39ooi SC, 9i 5, 9on-hurst OC* Ro#e of me"u##ary
CA/A, opioi"s, an" nociceptin in pro#on-e" inhibition of
car"iovascu#ar sympathoe4citatory ref#e4es "urin-
e#ectroacupuncture in cats* Am O 5hysio# &eart Circ 5hysio#
2007J29,?&,B27C&,B,8*
20* Crisostomo ++, 9i 5, 0Hen3A39ooi SC, 9on-hurst OC*
Nociceptin in r;9+ me"iates e#ectroacupuncture inhibition
of car"iovascu#ar ref#e4 e4citatory response in rats* O App#
5hysio# 2008J98?208BC20B,*
27* Rhou @Q, 0Hen3A39ooi SC, 9on-hurst OC* /rain stem
mechanisms un"er#yin- acupuncture mo"a#ity3re#ate"
mo"u#ation of car"iovascu#ar responses in rats* O App#
5hysio# 2008J99?887C8B0*
22* 0Hen3A39ooi SC, 9i 5, 9on-hurst OC* +e"u##ary
substrate an" "ifferentia# car"iovascu#ar responses "urin-
stimu#ation of specific acupoints* Am O 5hysio# Re-u# %nte-r
Comp 5hysio# 200AJ287?R882CR8B2*2,* 9i 5, Ro2shan N,
Crisostomo +, et a#* :ffect of e#ectroacupuncture on pressor
ref#e4 "urin- -astric "istension* Am O 5hysio# Re-u# %nte-r
Comp 5hysio# 2002J28,?R7,,8C7,A8*
2A* 0Hen3A39ooi, S*C*, 5* 9i, an" O*C* 9on-hurst, +i"brain
v#5AC inhibits r;9+ car"iovascu#ar sympathoe4citatory
responses "urin- e#ectroacupuncture* Am O 5hysio# &eart
Circ 5hysio#, 200B* 290B!? p* &28A,38,*
28* 9i 5, 0Hen3A39ooi SC, 9on-hurst OC* :4citatory
proHections from arcuate nuc#eus to ventro#atera#
peria6ue"ucta# -ray in e#ectroacupuncture inhibition of
car"iovascu#ar ref#e4es* Am O 5hysio# &eart Circ 5hysio#
200BJ290?&28,8C&28A2*
2B* Cuo R9, 9on-hurst O*C* :4pression of c-Fos in arcuate
nuc#eus in"uce" by e#ectroacupuncture? Re#ations to
neurons containin- opioi"s an" -#utamate* /rain Res
2007J77BB? B8C7B*
27* Rhou @, <u 9@, Cuo R9, 9on-hurst OC* Ro#e of
-#utamate in the rostra# ventro#atera# me"u##a in
acupuncture3re#ate" mo"u#ation of viscera# ref#e4
sympathoe4citation* Am O 5hysio# &eart Circ 5hysio#
2007J292?&78B8C&7878*
28* Rhou @, <u 9@, 0Hen3A39ooi SC, et a#* Ro#e of
-#utamate in a viscera# sympathoe4citatory ref#e4 in rostra#
ventro#atera# me"u##a of cats* Am O 5hysio# &eart Circ
5hysio# 200BJ297? &7,09C&7,78*
29* 0Hen3A39ooi SC, 9i 5, 9on-hurst OC* 5ro#on-e"
inhibition of rostra# ventra# #atera# me"u##ary premotor
sympathetic neurons by e#ectroacupuncture in cats* Auton
Neurosci 200,J 70B?779C7,7*
,0* 9i 5, Ayannusi O, Rei" C, 9on-hurst OC* %nhibitory
effect of e#ectroacupuncture :A! on the pressor response
in"uce" by e4ercise stress* C#in Auton Res
200AJ7A?782C788*
,7* &siao A3<, 0Hen3A39ooi SC, Rhou @* Neura#
path2ays of car"iovascu#ar "epressor ref#e4 "urin- -astric
"istension an" its mo"u#ation by e#ectroacupuncture*
<AS:/ O 2008J in press*
,2* 9ao 9, Rhan- C, @ei <, et a#* :#ectro3acupuncture
attenuates behaviora# hypera#-esia an" se#ective#y re"uces
spina# Fos protein e4pression in rats 2ith persistent
inf#ammation* O 5ain 2007J2?777C777*
,,* 9ao 9, Rhan- RL, Rhan- C, et a#* A parametric stu"y of
e#ectroacupuncture on persistent hypera#-esia an" Fos
protein e4pression in rats* /rain Res
200AJ70207C2!?78C29*
,A* 9i A, Rhan- RL, @an- Q, et a#* Corticosterone me"iates
e#ectroacupuncture3pro"uce" anti3e"ema in a rat mo"e# of
inf#ammation* /+C Comp#ement A#tern +e" 2007J7?27*
,8* Rhan- RL, 9ao 9, @an- L, et a#* :#ectroacupuncture
attenuates inf#ammation in a rat mo"e#* O A#tern
Comp#ement +e" 2008J77?7,8C7A2*
,B* Rhan- RL, 9ao 9, @an- 9, et a#* %nvo#vement of opioi"
receptors in e#ectroacupuncture3pro"uce" anti3hypera#-esia
in rats 2ith periphera# inf#ammation* /rain Res 200AJ
70207C2!?72C77*
,7* 9iu /*, Rhan- RL, @an- 9, et a#* :ffects of pertussis
to4in on e#ectroacupuncture3pro"uce" anti3hypera#-esia in
inf#ame" rats* /rain Res 2008J70AA?87C92*
,8* Rhan- RL, @an- 9, 9iu /, et a#* +u opioi" receptor3
containin- neurons me"iate e#ectroacupuncture3pro"uce"
antihypera#-esia in rats 2ith hin" pa2 inf#ammation* /rain
Res 2008J70A87C2!?2,8C2A0*
,9* 9i A, @an- Q, Lin O, et a#* :#ectroacupuncture
suppresses hypera#-esia an" spina# Fos e4pression by
activatin- the "escen"in- inhibitory system* /rain Res
2007J778B?777C779*
A0* Stener3;ictorin :, @a#"enstrom ., An"ersson SA,
@i$#an" +* Re"uction of b#oo" f#o2 impe"ance in the
uterine arteries of inferti#e 2omen 2ith e#ectro3
acupuncture* &um Repro" 799BJ7?7,7AC7,77
*
NAPADOW ET AL.868
A7* Stener3;ictorin :, <uHisa2a S, Nurosa2a +* Ovarian
b#oo" f#o2 responses to e#ectroacupuncture stimu#ation
"epen" on estrous cyc#e an" on site an" fre6uency of
stimu#ation in anestheti1e" rats* O App# 5hysio#
200BJ707?8AC97*
A2* Stener3;ictorin :, Nobayashi R, Nurosa2a +* Ovarian
b#oo" f#o2 responses to e#ectro3acupuncture stimu#ation at
"ifferent fre6uencies an" intensities in anaestheti1e" rats*
Auton Neurosci 200,J7087C2!?80C8B*
A,* +anneras 9, CaHan"er S, &o#man- A, et a#* A ne2 rat
mo"e# e4hibitin- both ovarian an" metabo#ic characteristics
of po#ycystic ovary syn"rome* :n"ocrino#o-y 2007J7A8?
787C,797*
AA* Stener3;ictorin :, @a#"enstrom ., 0a-nfors ., et a#*
:ffects of e#ectro3acupuncture on anovu#ation in 2omen
2ith po#ycystic ovary syn"rome* Acta Obstet Cyneco# Scan"
2000J 79?780C788*
A8* Chen /Q* Acupuncture norma#i1es "ysfunction of
hypotha#amicCpituitaryCovarian a4is* Acupunct
:#ectrother Res 7997J22?97C708*
AB* Cerhar" %, 5ostnee$ <* Auricu#ar acupuncture in the
treatment of fema#e inferti#ity* Cyneco# :n"ocrino#
7992JB?777C 787*
A7* Stener3;ictorin :, 9in"ho#m C* %mmunity an" beta3
en"orphin concentrations in hypotha#amus an" p#asma in
rats 2ith steroi"3in"uce" po#ycystic ovaries? :ffect of
#o2fre6uency e#ectroacupuncture* /io# Repro"
200AJ70?,29C ,,,*
A8* +anni 9, 9un"eber- 0, &o#man- A, et a#* :ffect of
e#ectroacupuncture on ovarian e4pression of a#pha 7!3 an"
beta 2!3a"renoceptors, an" p78 neurotrophin receptors in
rats 2ith steroi"3in"uce" po#ycystic ovaries* Repro" /io#
:n"ocrino# 2008J,?27*
A9* +annerSs 9, 9, Oons"ottir &, &o#mTn- A, et a#* 9o2
fre6uency e#ectro3acupuncture an" physica# e4ercise
improve metabo#ic "isturbances an" mo"u#ate -ene
e4pression in a"ipose tissue in rats 2ith "ihy"rotestosterone3
in"uce" po#ycystic ovary syn"rome* :n"ocrino#o-y
2008J7A9?,889C ,8B8*
80* Stener3;ictorin :, @a#"enstrom ., Ni#sson 9, et a#* A
prospective ran"omi1e" stu"y of e#ectro3acupuncture versus
a#fentani# as anaesthesia "urin- oocyte aspiration in invitro
ferti#i1ation* &um Repro" 7999J7A?2A80C2A8A*
87* @ester-aar" 9C, +ao M, Nro-s#un" +, et a#*
Acupuncture on the "ay of embryo transfer si-nificant#y
improves the repro"uctive outcome in inferti#e 2omen? A
prospective, ran"omi1e" tria#* <erti# Steri#
200BJ88?7,A7C7,AB*
82* An"erson /O, &aimovici <, Cinsbur- :S, et a#* In vitro
ferti#i1ation an" acupuncture? C#inica# efficacy an"
mechanistic basis* A#tern 0her &ea#th +e" 2007J7,?,8CA8*
8,* An"erson /O, Rosentha# 9* Acupuncture an" %;<
controversies* <erti# Steri# 2007J87?7000*
8A* +anheimer :, Rhan- C, ."off 9, et a#* :ffects of
acupuncture on rates of pre-nancy an" #ive birth amon-
2omen un"er-oin- in vitro ferti#isation? Systematic revie2
an" metaana#ysis* /+O 2008J,,B?8A8C8A9*
88* 5inbor- A, 9oft A, An"ersen AN* Acupuncture 2ith in
vitro ferti#isation* /+O 2008J,,B?877C878*
8B* )hon" R5, Nettner N, Napa"o2 ;* Neuroima-in-
acupuncture effects in the human brain* O A#tern
Comp#ement +e" 2007J7,?B0,CB7B*
87* &ui NN, 9iu O, +a$ris N, et a#* Acupuncture mo"u#ates
the #imbic system an" subcortica# -ray structures of the
human brain? :vi"ence from f+R% stu"ies in norma#
subHects* &um /rain +app 2000J9?7,C28*88* &ui NN, 9iu
O, +arina O, et a#* 0he inte-rate" response of the human
cerebro3cerebe##ar an" #imbic systems to acupuncture
stimu#ation at S0 ,B as evi"ence" by f+R%* Neuroima-e
2008J27?A79CA9B*
89* Napa"o2 ;, +a$ris N, 9iu O, et a#* :ffects of
e#ectroacupuncture versus manua# acupuncture on the human
brain as measure" by f+R%* &um /rain +app 2008J2A?
79,C208*
B0* @u +0, &sieh OC, Lion- O, et a#* Centra# nervous
path2ay for acupuncture stimu#ation? 9oca#i1ation of
processin- 2ith functiona# +R ima-in- of the
brain=Ipre#iminary e4perience* Ra"io#o-y
7999J272?7,,C7A7*
B7* 5ariente O, @hite 5, <rac$o2ia$ RS, 9e2ith C*
:4pectancy an" be#ief mo"u#ate the neurona# substrates of
pain treate" by acupuncture* Neuroima-e
2008J28?77B7C77B7*
B2* Non- O, Co##ub R9,* Rosman %S, et a#* /rain activity
associate" 2ith e4pectancy3enhance" p#acebo ana#-esia as
measure" by functiona# ma-netic resonance ima-in-* O
Neurosci 200BJ2B?,87C,88*
B,* )hon" R5, Qeh C, 5ar$ N, et a#* Acupuncture mo"u#ates
restin- state connectivity in "efau#t an" sensorimotor brain
net2or$s* 5ain 2008J7,B?A07CA78*
BA* Napa"o2, ;*, O* 9iu, +* 9i, N* Nettner, A* Ryan, N*N*
N2on-, N*N* &ui, an" O*<* Au"ette, Somatosensory cortica#
p#asticity in carpa# tunne# syn"rome treate" by acupuncture*
&um /rain +app 2007J28?789C777*
B8* Napa"o2 ;, Nettner N, Ryan A, et a#* Somatosensory
cortica# p#asticity in carpa# tunne# syn"rome=Ia cross3
sectiona# f+R% eva#uation* Neuroima-e 200BJ7?820C8,0*
BB* Napa"o2 ;, Nettner N, 9iu O, et a#* &ypotha#amus an"
amy-"a#a response to acupuncture stimu#i in carpa# tunne#
syn"rome* 5ain 2007J7,0?28AC2BB*
B7* @o#fe <, Ross N, An"erson O, et a#* 0he preva#ence an"
characteristics of fibromya#-ia in the -enera# popu#ation*
Arthritis Rheum 7998J,8?79C28*
B8* Coo$ )/, 9an-e C, Ciccone )S, et a#* <unctiona#
ima-in- of pain in patients 2ith primary fibromya#-ia* O
Rheumato# 200AJ,7?,BAC,78*
B9* Crace#y R&, 5et1$e <, @o#f O+, C#au2 )O* <unctiona#
ma-netic resonance ima-in- evi"ence of au-mente" pain
processin- in fibromya#-ia* Arthritis Rheum
2002JAB?7,,,C 7,A,*
70* &arris R:, C#au2 )O, Scott )O, et a#* )ecrease" centra#
muopioi" receptor avai#abi#ity in fibromya#-ia* O Neurosci
2007J27?70000C7000B*
77* Assefi N5, Sherman NO, Oacobsen C, et a#* A ran"omi1e"
c#inica# tria# of acupuncture compare" 2ith sham
acupuncture in fibromya#-ia* Ann %ntern +e"
2008J7A,?70C79*
72* )e#u1e C, /osia 9, Rirbs A, et a#* :#ectroacupuncture in
fibromya#-ia? Resu#ts of a contro##e" tria#* /+O
7992J,08?72A9C 7282*
7,* &arris R:, 0ian L, @i##iams )A, et a#* 0reatment of
fibromya#-ia 2ith formu#a acupuncture? %nvesti-ation of
nee"#e p#acement, nee"#e stimu#ation, an" treatment
fre6uency* O A#tern Comp#ement +e" 2008J77?BB,CB77*
7A* /ene"etti <, Aman1io +* 0he neurobio#o-y of p#acebo
ana#-esia? <rom en"o-enous opioi"s to cho#ecysto$inin*
5ro- Neurobio# 7997J82?709C728*
78* Chen L&, Ce##er :/, A"#er +@* :#ectrica# stimu#ation
at tra"itiona# acupuncture sites in periphery pro"uces brain
opioi"Creceptor3me"iate" antinociception in rats* O
5harmaco# :4p 0her 799BJ277?B8ACBB0*
7B* Shah O5, )anoff O;, )esai +O, et a#* /iochemica#s
associate" 2ith pain an" inf#ammation are e#evate" in
sites near to an
"
A',P,N'T,)E #E'-ANIS# )ESEA)'- 86=
remote from active myofascia# tri--er points* Arch
5hys +e" Rehabi# 2008J89?7BC2,*
77* 9an-evin &+, /ouffar" NA, /a"-er CO, et a#*
Subcutaneous tissue fibrob#ast cytos$e#eta# remo"e#in-
in"uce" by acupuncture? :vi"ence for a
mechanotrans"uction3base" mechanism* O Ce## 5hysio#
200BJ207?7B7C77A*
78* 9an-evin &+,
/ouffar" NA, Churchi## )9,
/a"-er CO* Connective
tissue fibrob#ast response to
acupuncture? )ose3
"epen"ent effect of
bi"irectiona# nee"#e rotation*
O A#tern Comp#ement +e"
2007J7,?,88C,B0*A""ress
reprint re6uests to? Vitaly
Napadow, Ph.., !ic."c.
Martinos #enter $or Bio%edical
I%aging Massachusetts &eneral
'ospital
Building ()*, (+th
,treet -oo%
.+/(01NM- #enter
#harlestown, M"
/.(.*
2-%ail3
vita#yUmnr*m-h*harvar"*e"u