(pmaT)mtmclewas evokedbydeetrical stimulat

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9756 Ac口phar
r
namk笔I
ca
Si
ni
c
a 中 国药理 学报 1997 J
ul
;1
8(4):37
7—379
K etam i
ne-
induced peri
pheral
analgesi
a i
n rats
BAI
Li
,ZHAO Zhi
—
Qi
(Shanghai
Br
ai
n Re
s
e
arc
h I
ns
t
i
t
ut
e,Chi
nes
e
Ac
ademy o
f Sci
enc
e
s,Shanghai
200031,Chi
t
n)
i
ket
m'
ni
ne; el
e
ct
ri
c
s
t
i
mul
at
i
on;
(Sha ̄
ghm Ani
mal
Cent
er. Chi
nes
e Ac
ade
my 0f
Sci
ence
s)
ehct
m myogr
aphy; pa
i
n n ̄
ea
su_
v
e
r
ne
nt; a
l
ml
ge
s  ̄;
we
r
e
a
ne
s
t
he
t
i
z
e
d wi
t
h u
r
e
t
h
a
ne(1.
1’
g‘k
g ,i
p,i
ni
t
i
a
l
l
y)
ml
oxone n d f
a
i
xed i
n a st
er
eot
axi
c f
r
ame KEY W ORDS Body t
e
m per
at
ure, t
he ml
or
of
t
e pl
h
ant
ar
reCi
c ̄. and bl
ood pr
es
sur
e w AI
N :To e
xan1
i
r
l
e
whet
上
1
e
r
kemmi
ne may di
r
et
c
l
y ac
t
at
per
i
phe
r
al
noe
i
e pt
c
or
s
t
o pr
oduc
e a
1
1
al
nmi
nl
mne
d i t
w
hi
n nor
r
r
m【I
i
mi
t
s.
As
a
no
e
i
e
e
pt
i
v
e
f
lex
i
on
r
e
f
l
e
x (FR), t
e f
h
i
r
i
ng 。f
a_
Ⅳ匝T}I
(I
DS: W i
s
t
ar
r
at
s we
.
1
 ̄ ane
st
het
i
ze
d wi
t
h ur
et
l
ume. As anoe
i
e
ept
i
vef
le
xi
on r
ef
l
ex(FR),C r
e
s
ponse
s
f
r
om t
he
p0劬 。I
bi
c
eps
s
emi
t
endi
ne
e
us
(
pma
T)mt
mc
l
ewa
s
e
v
o
ke
dbyde
e
t
r
i
c
a
l
s
t
i
mu
l
a
t
i
on
(
2 r
ns,80 V ,2—3 pI
l
l
£
8 ,0,
5}k)vi
a a pa
i
r
cf
de
ct
r
c
xnyogra
phy (EMG ) f
r
r
ma t
he I
:
ost
e
ri
c ̄ bi
c
eps s
e
rni
t
endi
nosus (PBST ) mus
cl
e wan
e
voke
d by dect
r
i
caI
s
mnul
at
l
ce
l(2 ,80 V,0.
5 Hz,2— 3 pul
s
es.at
5一
mi
n i
nt
er
val
s) vi
a a pai
r of
s
t
ai
nl
ss
e
st
e
el
nee
dl
e
s i
ns
ert
ed s
ub
c
u
t
a
ne
o
us
l
y
t
o t
e h
t
wo t
o
e
s
o
f
i
ps
i
l
a
t
e
r
l a
hi
n
dp
a
w【
r0
obt
a
i
n a st
abl
e re
cor
di
ng.ur
et
hane wa
s s
uppl
ement
d "
e
t
o keep s
t
ai
nl
e
s
s st
ee
l
ne
edl
e
s i
ns
er
t
e
d s
ubc
ut
ane
ous
l
y a
st
abl
ea
n e
st
hes
i
a. Th
e f
i
r
i
ng of
EM G wa
s ave
rage
d a"
t
5 a
ppl
i
d t
e
o t
he t、
∞
mi
n i
nt
e
rv
al
s n d a
a
s
t
bl
a
e bas
el
i
neⅥ as
e
s
t
abl
i
she
d f
呵 a"
t
1
e日
5 t
oe
s
of
i
ps
l
t
at
er
al
hi
ndpaw.
RESULTS;Su ̄ nanmusi
nj
ct
e
i
on of
ket
ami
ne(36 mr
r
 ̄l・L ,5 止 ) i
nt
o t
he
i
ps
i
t
at
er
al
hi
ndp
sw 20 mi
nh
ef
or
e me
di
cat
ion. The
dr
ugswe
r
ei
nj
ect
d sci
e
n"
t
o pr
oduc
ed R
n i
bi
t
i
on of
C r
es
pons
es. At
9 r
ai
n ke-
t
a
mi
ne on FR wa
n expr
es
se
d a
n -
the cha
r
窖e i
n "
t
he
r
ef
l
ex a
f
t
er
appl
i
c
at
ion f o
ke
t
a
mf
ine,
m gni
nJ
de∞ m pa eet
i
on of
m l
mmne (1% ,5止 )i
nt
ot
he鼬l
I
l
e ar
ea
annul
l
edket
 ̄ni
ne-
n duc
i
e di
nl
'
ibi
f
ion. c0N口LUS 0N:Ket
f
ami
ne a
s a
di
s
s
oci
at
eane
s
t
he
t
i
cac1
.
sonper
i
pher
alnoc
i
e pt
c
om t
o t
he paw e"
h
t
wee
 ̄ the "
t
wo hi
nd—
0 st
imul
at
d . T he e
ef
f
ect
of
王 ± a
n d ana
ly ̄
R ESULTS pr
oduc
e a
1
l
aI
g目i
a,whi
ch i
s
r
e
l
at
e
d t
o a
ct
i
vi
t
y of
per
ipher
alor
 ̄oi
d r
e
cept
or
s.
t
o bas
eh e The dat
a w盯 e。中r
e龉d as by t t
st
e
The fi
ri
ng of EM G i
n PBST refl
ex by el
ectr
ic st
l
m ul
ati
on of
hi
nd-
di
gl
ts exhi
bi
te
d two c
omp
o n.
ents, t
he A resp
o nse with a short l
at
ency and C Ketar
ni
ne as
a di
ss
oci
ate anest
het
i
c at
very l
ow dos
e(0.
2
mg・
一
)pr
oduces
anal
ge
s
i
c
ef
f
ec
t
i
n cl
i
ni
c[11
. Si
noe ket
ne i
s a sel
e、Ti
ve cl
1
anr
l
ant
a
goni
st
f
or
N—
met
hyl
—
D—
a
spa
r
t
at
e (NMDA )
r
e
s
o ns
p
e wi
t
h a
l
ong l
at
enc
y (Fi
g 1),whi
ch wer
e evoked by A—and C-
af
ferent
i
nput. respecti
vel
y J.
In thi
s
st
udy, noci
e pt
c
i
ve C c
o m ponent
i
n t
he lexi
f
on ref
lex wa
s t
s ted.
e
recept
or, the c
e nt
ral
m echani
sm of ketam i
ne-
i
nduced anal
ge
si
a may be attri
but
ed to bl
ockade of N ~I
DA recept
or—
m edi
ated spi
na
l t
ransm i
ssi
on of
no
ci
ee[
]
ti
ve i
nform ati
on[
2,
31
However. i
n our Ket
a
mi
ne i
nj
ec
t
d i
e
nt
o t
he i
ps
i
l
at
e
r
al
hi
ndpaw pr
oduced a m arke
d i
nhi
bi
ti
on of C re
sp
o nses
i
n FR .
Fi
ve
i nut
m
es
a
f
t
er
i
ni
e
ct
i
on of
ket
a
mi
ne (36 mmol
.
prev
ious study , i
t
has been shown t
hat
t
opi
cal
appl
i
c
at
i
on of
ket
ami
ne t
o t
he per
i
pher
a
l
ner
ve
powerful
l
y bl
c ke
o
d nerve conducti
on, sugge
s ti
ng t
hat per
iphera
l m echani
sm mi
ght
be i
nvol
ved i
n ana
lgesi
c ef
fect
of ket
al
l
r
l
l
ne T he ai
m of
thi
s work was t
o ana
lyze the peri
pheral
n al
a
gesi
a of ket
am i
ne.
‘
L一
,5 L), t
he
aver
a
ge
d C r
sp
e
o ns
es 、
r
e
r
d uce
e
d by40 % ±7 % (
= 4).whi
c
hr
et
ur
ne
d t
o I
l
orma
l l
e
vel
30 mi
n af
t
e
r
i
ni
ect
i
on of
ket
a
mi
ne.
I
n contra
s t,
i
psi
l
at
era
l ecti
on of sal
i
ne or ont
c
r
lat
a
er
a
l
i
nj
ct
e
i
on of
ket
a
mi
ne
at
t
he S
s
3
3
f
l
e
dose
f
ai
l
ed to pr
oduc
e i
nhi
bi
ti
on ofC re
sp
o nse. W h吼 a hi
gh dos
e of
ke
t
a
mi
ne(180 mmol
・L
,5 L,s
c)
was
i
ps
i
l
at
er
ll
a
y
i
nj
ct
e
d ,C r
e
e
sp
o ns
e
s i
n FR wer
e
M ATERIALS AND M叮 H0DS si
gni
f
i
c
nt
a
l
y r
d uc
e
edby 85 % ±7 % (
=4). The
wi
 ̄
t
ar r
at
s(
= 15 we
i
ghr
i
ng 278 ± Cor
r
e
 ̄ ndenc
e t
o ZHAO Zhi
—
Qi
,pl
a
n:86 21
45
474—
8700 Re
cei
ved 1
99
641
1—
23 Ac
ce
pt
ed 199741
2
-19
24 g i
nhi
bi
t
i
on l
st
a
e
d over
30 mi
n (Fi
g 2).
Dur
i
g the maxi
n
ma
l i
nhi
bi
ti
on by ketam i
ne,
1 % na
loxone(5
L)wa
s i
nj
ect
d s
e
ei
nt
ot
he
8
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Ac
t
a Pl
 ̄r
mac
obgi
m Si
t
ic
f
a 中国 药理 学报 1
997 Jul
;18(
4)
ket
a
mi
ne
—
i
nduc
ed i
nhi
bi
t
i
on W hen ket
a
mi
ne(180 \¨0;
o*■ I
Y
I
I
TI
OI_
LI
1)was
appl
i
d t
e
o t
he
c
ont
r
a]
ate
r
al
hi
nd toes. 1
ess i
nhi
bi
ti
on of C r
esp
o nses w as obt
ai
ne
d (36 % ±8 % ,
二 5). The
r
ecover
yt
i
mewas
20 mi
n. whi
ch was
s
hort
er
t
ha
n t
hat
of
i
ps
i
l
at
e
r
al
i
n
j
ct
e
i
on-
i
nduce
d i
nhi
bi
t
i
on(Fi
g 3).
Ti
me/mi
n 3. 叫 0f5肚 m 0.
1% sc
9mi
n af蛔 ke伽 札I
玎e
-h山 。e
d-
nl
枷 叫 0fC 砘 叩 0T
b嚣 el
"
n目嘶 n  ̄ t
'
l
ex.
,
弓-∞co4¨∞z 4 .
± .
< O.
05,c
p<O.
0l傩 ,
 ̄al
x
ol(
c打).
To t
es
t
l
oca
l
anes
t
he
t
i
c
ef
f
e
ct,ke
t
ami
ne(180 眦 m I_L ) pr
oduc
ed a
c
onpl
et
e i
nhi
bi
t
i
on of
C response
s wer
e sel
ct
e
d i
e
n t
he 4 rat
s.
5o 10o 150 2∞
250 300 W hen the CU/
Te
Dti
nt
ens
i
t
yof
st
i
mul
at
i
onwas
enh
a nc
e
d ff
r
om Ti
me/m l
n 80 V ,2 pu
ls
es
t
o 1
00 V, 5
pu
ls
es) dur
i
ng t
he
per
i
od of i
nhi
bi
t
i
on, C re
sponses were sti
l
l
evoke
d .
ng 1.  ̄ dbi
t
l
on m C re
spo ̄e of fl
e ̄ m ref
lex l
【
e
诅I
ni
(
3
6 m
mmo
l
-
L-
,5
pL).
o
f4 r
e
s
p0
m .
I
n c
ont
r
a
st, when C r
sp
e
o ns
e was
i
nhi
bi
t
d by
e
pr
oc
ai
ne(1% ,5 L)i
nst
e
ad of
ket
ami
ne,i
ncr
e
as
-
i
ng currentfai
l
d t
e
o evokeC r
esp
o nse.
DIsI
口 J
卫0N The resul
t
s f
i
rst
demonst
rate
d that
ketam i
ne di
r
ect
l
y act on the per
ipher
al
recepti
ve f
i
el
d,w here there exi
st
abundant
noci
o pt
c
ors.
幻
pro
d uce a
nal
ge
si
a.As
ke
t
a
r
r
ine
f
i
s
a ce
nt
r
a
l
ane
st
het
i
c
s,an i
nvol
vem ent
of
t
he central
act
i
on i
n i
nhi
bi
ti
on of
C r
e
sp
o ns
es
woul
d be o2
)
I
1
8i
der
e
d due
t
。t
he
di
f
f
us
i
on of
dr
ugs.
I
f
t
hi
s ca
s
e occ
urs, t
he
e wou
r
ld b
e n0 di
f
f
er
enc
e b
et
win i
ps
i
—a
nd c
ont
r
a-
-
l
at
er
a
l
appl
i
ca-
-
Ti
me/m i
t
i
on of dru .
ri
g7
-- Ef
f
eci。f kt
e
mmbl
e on C sl
Ⅻ
(
4)
i
ec
t
i
吼 0fs
of f
,
∞d
Ⅲ
rdl
ex o
f
s
a
l
i
neo
r
ke
t
n
mi
ne36旺 1
80 I
帅 砷l
・L-。. b
P< O.
05,
< O.01催 s
ali
ne.
However,
ketamine-i
nduce
d i
nh{
bi
t
i
on at
a l
ow dos
e (36 mmol・L ) was
pr
oduc
d onl
e
y by i
t
s
i
p ̄
<l
at
er
a
l
appl
i
c
at
i
on.
Al
t
hough t
he
o nt
c
r
al
at
er
al
a
ppl
i
at
c
i
on of
ket
mni
ne at
ar
ea. Ket
ar
nl
ne
 ̄i
nduced i
nhi
bi
ti
on wr
i
t
s com pl
et
el
y a hi
gh d0s
e (1
80 mmol‘L。。) al
s
o pr
oduc
ed an annul
l
e
d 10 r
ai
n a
f
t
e
r
i
nj
e
ct
i
on of
nal
oxone,whe
re
as
i
nhi
bi
ti
on of
C r
sp
e
o nse
s
t
he
r
e was
no e
f
f
e
ct
of
i
nj
ct
e
i
on of
s
al
i
ne
on act
i
ons,t
he i
nhi
bi
t
i
on by i
psi
l
at
e
r
al
appl
i
at
c
i
on was
 ̄
,
suggesti
ng i
ts centr
al
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9756 Act
s P ̄
eo
l
gl
n
c
a Si
ni
c
a 中国 药理 学报 m uch p
o w erf
ul
than th
at
by contral
at
era1. T hese data show ket
am i
ne-i
nduced peri
pheral
anal
gesi
a.
The m eehani
sr
r
 ̄
s
of
ketami
ne—
i
nduced er
p
iph
a ml
anal
gesi
a remai
n uncl
e
ar.
II
1
t
he earl
i
er i
vitro studi
es
(6
r
19
97 Jul
;18(4)
dor
s
l a
hom n
ocl
c
e ̄ i
ve
neur
ons f
 ̄l
o
wi
ng C ibr
f
e
s
t
i
mul
at
io
n Neul
o
ph
ar
ma
c
ol
g y 198
n
7;26:1235—8 4 SongⅪ ,gha
ng JF,Ze
ngYM ,ZhaoZQ Ef
f
e
e ̄
s
of
t
a
nf
ine叽 c
c
0
a
d
uet
i
o
n of
pe
nphe
 ̄t
n
Cbi
n J
Pme
st
hes
l
o[199
5;1
5:446—9 bot
h sodi
u1
7
1
and potassi
um 5 Zh
a ngKM .Zhz
oZQ. 8e
l
e
et
i
ve bl
oc
k
ad
ebyyohi
mbi
ne
ofl
oc
us
cha
n nds
were af
fected by ketami
ne i
n the m eml
e
u
s-
i
nduc
e
dl
t
t
hi
bi
donof
n
oc
i
ee
pt
i
ve
r
e
le
f
xbut
nott
h
at
0fC ay
r
el
i
nat
e
d R
xons,s
ugge
st
i
ng t
at
h
ket
a
mi
ne—
i
nducod
r
e
s
l
xXt
s
es
0f
s
Dl
na
l
d0i
¥ ham i
l
et
u
3
 ̄
bl
ockage of
conduct
i
on of
the peri
phera
l nerve Act
a Ph
e
a ̄mco
l
Si
n 1994; 1
5:491— 4 .
probabl
y r
esul
te
d from non—
synapt
i
c i
nhi
bi
t
i
on of
Na current. Si
ne
a there was no eff
ect
of ketam i
ne on i
nacti
vati
on of Na current
(6] ket
am i
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eems .
l
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of
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r J
Phmmac
d 19
86:126:245—52 7
B ̄l
i
otE, ̄,
a
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lM R,Duh
ai
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o di
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onlt
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i
c
s
Thef
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a
ct
i
n of
o
ket
m /ne i
n t
h
e ct
t
r
r
ent
a
nd vo[
t
 ̄ e there exi
sts a di
f
ference between ket
am i
ne- and dm 【
d r
a
ye
l
i
 ̄ t
ed ne
r f
ibr
e
o
f
t
h
e f
r
o
g.
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ne-i
nduce
d ef
fe
c ts and na
loxone revers
es ket
am i
ne-i
nduced i
nhi
bi
ti
on i
n our study supp
o rt
thi
s vi
ew .
Br
J
Pt
mrmac
ol
1986}87:291—7 8 St
ei
nC,
蛐
A .Gramsch C,HeraA ,
L。c
opk ̄
i
d
r
ec
e
pt
or
s
med
 ̄
a
t
/
g n
mat
/
noc
i
c
ep
uon m i
n/
/
a
m ma ̄
i
on:
e
ndo
genous ̄ga
nds I
n:Bond M R,Ch
ar
l
am JE,w 。 a ,
The
opi
oi
d r
ecept
or
s are dens
el
y di
str
ibuted i
n t
he peri
pheral
nerve t
erm i
nal
s
and ar
e i
m pl
i
cat
ed i
n n ti
a
no
ci
a pti
e
on(8
In t
he
present
study, r
e versal
. of
ke
t
ami
ne
qnduced pe
ipher
r
al
ana
l
ge
si
a
by na
loxone st
rongl
y su
g gests t
at
h
the at
'
l
i
on of
ket
ami
ne i
s cl
osel
y tel
ated t
o acti
vi
t
y of
peri
pheral
opi
oi
d recept
ors.
e
di
t
or
s
Pr
oc
e
ed
i
ngs
of
t
he
Vhh W 0r
l
d & w 瑚 s∞ Pai
n Ar
 ̄t
e
r
dam :El
s
ev
i
e
r.1
991:83— 7
9 W es
dt
md KN Lawa
ndNB.W L
I
EsW D Ex
ci
t
at
or
y舢
(
EAA) i
n t
he p
er
i
ph
er
y c
 ̄
mt
r
i
bu
t
e
t
?
o t
he d
evdot
m ̄mt
of
a
uodyni
a
a
nd
t
hem ml
hypo
r
al
ge
s
i
a
i
n a
r
t
l
 ̄i
t
l
c
ra
s.
t
77
S
—
a
c
氯氨酮引起的太 鼠外周镇痛作 用 As Rl
enti
oned i
n i
ntr
oducti
on. ket
amine as a R 7/~
2
NM DA recept
or a
nt
agoni
st
produces i
nhi
bi
ti
on of noeic
ept
i
ve r
es
o nses of
p
pa
in-sensi
ti
ve neur
on i
n t
he spi
na
l c
ur
dI
.
a
c
j
ds
(中国科学 院上 海脑 研究所 ,上海 20
0031,中 国)
A recent
r
ep
o rt
showed that
gl
ut
amate, aspar
t at
e a
n d ar
gi
ni
ne concent
rati
ons i
n r
at
knee
j
oi
nt
e
avi
t
y wer
e i
ncr
e
as
e
d wi
t
h i
nf
l
a
mmat
or
y pai
n[
9]
. 关键词 氯氨酮;电捌激;肌电描记术;测痛;镇锄 痛;纳蜥 一 一
1、
her
e
f
or
e. i
t
s
houl
d b
e oons
i
de
r
ed whet
her
NMD A r
ec
ept
or
mi
ght
b
e 目的 ;研究 氯 氨酮是否 可 以直接 作用 于外 周 伤害 oont
ri
bute
d 性感受器而产生镇痛 . 方法 ;一 对不 锈钢针 插入 t
o ket
am i
ne-i
nduced per
ipheral
n al
a
gesi
a.
尿醇麻 醉的大 鼠一 侧后 肢 的两 足脂皮 下 ,施加 强 电流(
2
n1
s
,8
0
v,2—3脉 冲 ,0.
5}
k)作 为伤 害 性 刺 激 ,在 同 一 后 肢 的后 二 头 半 腱 肌 记 录 肌 电 反 1
U ni
t
e
d St
a
t
e
s P 仉 r
qod口 I
Convent
i
on USP DI
i
nf
or
r
r
mt
i
on f
or
t
he
hml
t
h ca
r
e pr
of
e
v
:
,
 ̄o
nal
1
5t
h
ed Roc
k ̄l
I(
):USPc,1988:1647
2 Song XJ, Zhao ZQ I
nt
e ̄di
c
m bet
wee
n s
ubs
t
a
nc
e P a
nd exc
i
t
a
t
or
y
"a
mi
n
o a
ci
d
r
e
c
ept
or
s
i
n mo
dul
at
i
on of
no
ci
c
ept
i
ve
r
ml
xx
1
.
s
es
of
t
s
dor
s
al
hor
n r
l
eu
r
c
 ̄
 ̄ Net
m ̄ i
Lett
19 : 168:49— 52 3 Ⅱ c
ke
ns
on AH .
l
i
va
n AF E dea
ce
f
or
a r
ol
e
of
NM 【
)A r
ec
ept
or
i
n t
he
f
r
e
quenc
y depe
nde
nt
pot
 ̄l
ia
f
ti
on of
de
ep r
at
应 。电刺 激引起 的长潜伏 期 C成 分 ,作 为 伤害 性 屈反射 的指标 , 结果 :在邻近刺激 电极 的跖部 皮 下注射氯 氨酮(
3
6 mmo
l
・
L~。5正 )
可 明显 抑箭 C 反应 ,注射 氯氨 酮 后 9分钟 ,在 同一 部 位 注射 5
‘
‘
L的 1%纳络酮 ,可翻转抑制效应 , 结 论 :氯氨 酮可 直接 作用 外周 伤 害性感 受器 产生镇 痛 ,并提 示可 能与外周 阿片受体 的激 活有关 ,