Research Signpost 37/661 (2), Fort P.O., Trivandrum-695 023, Kerala, India Cellular and Molecular Mechanisms for the Modulation of Nociceptive Transmission in the Peripheral and Central Nervous Systems, 2007: 1・22ISBN: 81-308・0162-0 Editor: Eiichi Kumamoto
The c
o
n
t
r
o
v
e
r
s
i
a
l
i
s
s
u
e
o
f
t
h
e
s
y
n
a
p
t
i
c
s
t
r
u
c
t
u
r
e
u
n
d
e
r
l
y
i
n
g
p
a
i
n
m
o
d
u
l
a
t
i
o
n
i
n
t
h
e
s
u
p
e
r
f
i
c
i
a
l
d
o
r
s
a
l
horn
o
f
t
h
e
s
p
i
n
a
l
c
o
r
d
Akio Hiura Department of OraJ Anatomy. School of Dentistry. Tokushima University 3-18・15.Kuramoto-cho. Tokushima 770-8504.炉panA
b
s
t
r
a
c
t
At present, the occurrence0
1
jirst modu/'αuon0
1
pain transmission in the superjicial dorsal horn, especially in the substαntiαgelatinosa (SG: laminα 11), is jirmly estab!
i
shed
.
Nociceptive primaηα
, rfferent central terminals (C-terminal
)
ぽisi哩介omnonmyelinated C-
f
i
bersαnd myelinated As
-
.
jibers terminαte in theSGα
ndmα
rke synaptic glomeruli, in which theyα
're centrally situα
tedα
nd surrounded bya number0
1
dendrites and Correspondence/Reprint request:Dr. Akio Hiura, Department of Oral Anatomy, School of DentistryTokushima University, 3-18-15 Kuramoto-cho, Tokushima 770・8504,Japan E・mail:hiuraaki@dent.tokusluma-u.acj.p
2 Akio Hiura
a
few a
x
o
n
a
l
t
e
r
m
i
n
a
l
s
.
One of t
h
e
s
t
r
u
c
t
u
r
a
l
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
of C
-
t
e
r
m
i
n
a
l
s
i
s
i
n
d
e
n
t
e
d
,s
i
n
u
o
u
s
,o
r
s
c
a
l
l
o
p
e
d
e
l
e
c
t
r
o
n
-
d
e
n
s
e
a
x
o
p
l
a
s
m
f
u
l
l
of
r
o
u
n
d
s
y
n
a
p
t
i
c
v
e
s
i
c
l
e
s
(
C
l
-
t
e
r
m
i
n
a
l
)
,w
h
i
l
e
an o
t
h
e
r
i
s
l
a
r
g
e
r
r
o
u
n
d
i
s
h
,e
l
e
c
t
r
o
n
-
l
u
c
e
n
t
似
o
p
l
a
s
mw
i
t
h
many l
a
r
g
e
d
e
n
s
e
c
o
r
e
v
e
s
i
c
l
e
s
and m
i
t
o
c
h
o
n
d
r
i
a
(
C
l
l
-t
e
r
m
i
n
a
l).T
h
e
y
a
r
e
FRAP-and S
P
-o
r
C
G
R
P
-
p
o
s
i
t
i
v
e
and show i
n
t
e
n
s
e
c
a
p
s
a
i
c
i
n
-s
e
n
s
i
t
i
v
i
t
y
.
l
n
h
i
b
i
t
o
r
y
i
n
t
e
r
n
e
u
r
o
n
s
c
o
n
t
a
i
n
i
n
g
GABA
,g
l
y
c
i
n
e
o
r
o
p
i
o
i
d
s
a
r
e
e
x
c
l
u
s
i
v
e
か
p
r
e
s
e
n
ti
n
t
h
e
S
G
.
T
h
e
y
c
o
n
t
a
c
t
w
i
t
h
C
-
t
e
r
m
i
n
a
l
s
,f
o
r
m
i
n
g
s
y
n
a
p
t
i
c
g
l
o
m
e
r
u
l
i
.
However
,t
h
e
s
y
n
a
p
t
i
c
r
e
l
a
t
i
o
n
s
h
i
j
ヮb
e
t
w
e
e
nC
-
t
e
r
m
i
n
a
l
s
and i
n
h
i
b
i
t
o
r
y
i
n
t
e
r
n
e
u
r
o
n
s
i
s
c
o
n
t
r
o
v
e
r
s
i
a
l
,i
.
e
.
,t
h
e
p
o
s
t
s
y
n
a
p
t
i
c
c
o
n
t
a
c
t
s
of i
n
h
i
b
i
t
o
l
アi
n
t
e
r
n
e
u
r
o
n
s
t
o
C
-
t
e
r
m
i
n
a
l
s
i
s
n
o
t
a
c
c
e
p
t
e
d
.
However
,from p
r
e
v
i
o
u
s
r
e
p
o
げSc
o
n
c
e
r
n
i
n
g
t
h
e
s
e
s
y
n
a
p
t
i
c
s
t
r
u
c
t
u
r
e
s
,t
h
e
p
r
e
s
y
n
a
p
t
i
c
陀l
a
t
i
o
n
s
h
i
pof
Cてf
i
b
e
r
s
t
o
t
h
e
i
n
h
i
b
i
t
o
r
y
i
n
t
e
r
n
e
u
r
o
n
s
seem t
o
b
e
more e
n
h
a
n
c
e
d
,a
l
t
h
o
u
g
h
s
p
e
c
i
e
s
d
i
f
f
e
r
e
n
c
e
s
m
i
g
h
t
b
e
p
r
e
s
e
n
t
.
A
b
b
r
e
v
i
a
t
i
o
n
s
AChE: A
c
e
t
y
l
c
h
o
l
i
n
e
s
t
e
r
a
s
e
, ACTH: A
d
r
e
n
o
c
o
r
t
i
c
o
t
r
o
p
i
c
hormone
,
APP: A
v
i
a
n
p
a
n
c
r
e
a
t
i
c
p
o
l
y
p
e
p
t
i
d
e
,
CAL: C
a
l
r
e
t
i
n
i
n
,
CB: C
a
l
b
i
n
d
i
n
-
D
2
8
K
,
CCK: C
h
o
l
e
c
y
s
t
o
k
i
n
i
n
,
CGRP: C
a
l
c
i
t
o
n
i
n
g
e
n
e
-
r
e
l
a
t
e
d
p
e
p
t
i
d
e
,
ChA
T
:
C
h
o
l
i
n
e
a
c
e
t
y
l
t
r
a
n
s
f
e
r
a
s
e
, DOP: Dopamine, DYN: Dynorphin, ENK:
E
n
k
e
p
h
a
l
i
n
,
FRAP: F
l
u
o
r
i
d
e
-
r
e
s
i
s
t
a
n
t
a
c
i
d
p
h
o
s
p
h
a
t
a
s
e
,
GABA:
1
-A
m
i
n
o
b
u
t
y
r
i
c
a
c
i
d
,
GAL: G
a
l
a
n
i
n
,
GLU: G
l
u
t
a
m
a
t
e
(
G
l
u
t
a
m
i
c
a
c
i
d
)
,
GluRl
・4
:
AMPA-type g
l
u
t
a
m
a
t
e
r
e
c
e
p
t
o
r
,
GluR5
・7
:K
a
i
n
剖e
-
t
y
p
eg
l
u
t
a
m
剖er
e
c
e
p
t
o
r
,
GL
Y
:
G
l
y
c
i
n
e
,
H
I
S
:
H
i
s
t
a
m
i
n
e
,
5
・HT:5
・H
y
d
r
o
x
y
t
r
y
p
t
a
m
i
n
e(
S
e
r
o
t
o
n
i
n
)
,
I
B
4
:
I
s
o
l
e
c
t
i
n
84
,
L-ENK: L
e
u
c
i
n
e
-
e
n
k
e
p
h
a
l
i
n
,
M-ENK: M
e
t
h
i
o
n
i
n
e
-
e
n
k
e
p
h
a
l
i
n
,
NA: N
o
r
a
d
r
e
n
a
l
i
n
e
,
NADPH
・d
:N
i
c
o
t
i
n
a
m
i
d
e
a
d
e
n
i
n
e
d
i
n
u
c
l
e
o
t
i
d
e
p
h
o
s
p
h
a
t
e
d
i
a
p
h
o
r
a
s
e
,
NMDAR: NMDA-type g
l
u
t
a
m
a
t
e
r
e
c
e
p
t
o
r
,
NP: N
e
u
r
o
p
h
y
s
i
n
,
NPY: N
e
u
r
o
p
e
p
t
i
d
e
Y
,
NT: N
e
u
r
o
t
e
n
s
i
n
,
OXY: O
x
y
t
o
c
i
n
,
P2X
3:A
T
P
-
g
a
t
e
d
r
e
c
e
p
t
o
r
,
Re
t
:
GDNF r
e
c
e
p
t
o
r
k
i
n
a
s
e
,
SOM: S
o
m
a
t
o
s
t
a
t
i
n
,
S
P
:
S
u
b
s
t
a
n
c
e
P
,
TRH: T
h
y
r
o
t
r
o
p
i
n
-
r
e
l
e
a
s
i
n
g
hormone
,
T
r
k
A
:
NGF r
e
c
e
p
t
o
r
t
y
r
o
s
i
n
e
k
i
n
a
s
e
,
V
I
P
:
V
a
s
o
a
c
t
i
v
e
i
n
t
e
s
t
i
n
a
l
p
o
l
y
p
e
p
t
i
d
e
,
VR1: V
a
n
i
l
l
o
i
d
(
C
a
p
s
a
i
c
i
n
)
r
e
c
e
p
t
o
r
1
(TRPVl)
,
V
紅1
:V
a
n
i
l
l
o
i
d
r
e
c
e
p
t
o
r
-
l
i
k
e
1
(
T
R
P
V
2
)
.
I
n
t
r
o
d
u
c
t
i
o
n
T
h
e
r
e
h
a
v
e
b
e
e
n
n
u
m
e
r
o
u
s
s
t
u
d
i
e
s
on t
h
e
f
i
n
e
s
t
r
u
c
t
u
r
e
o
f
t
h
e
s
y
n
a
p
t
i
c
r
e
l
a
t
i
o
n
s
h
i
p
o
f
t
h
e
n
o
c
i
c
e
p
t
i
v
e
p
r
i
m
a
r
y
a
f
f
e
r
e
n
t
c
e
n
t
r
a
l
t
e
r
m
i
n
a
l
s
(
C
-
t
e
r
m
i
n
a
l
)
t
o
t
h
e
i
n
h
i
b
i
t
o
r
y
i
n
t
e
r
n
e
u
r
o
n
s
,
u
s
i
n
g
i
m
m
u
n
o
e
l
e
c
t
r
o
n
m
i
c
r
o
s
c
o
p
i
c
m
e
t
h
o
d
s
,
合om1
9
7
0
t
o
d
a
t
e
.
The
e
x
a
c
t
i
n
t
e
r
r
e
l
a
t
i
o
n
s
h
i
p
b
e
t
w
e
e
n
C
-
t
e
r
m
i
n
a
l
s
a
n
d
i
n
h
i
b
i
t
Ol)'i
n
t
e
r
n
e
u
r
o
n
s
i
s
n
o
t
y
e
t
c
l
e
a
r
,
b
e
c
a
u
s
e
t
h
e
d
e
m
o
n
s
t
r
a
t
i
o
n
o
f
p
t
・e
-o
r
p
o
s
t
s
y
n
a
p
t
i
c
c
o
n
t
a
c
t
s
o
f
C
-
t
e
r
m
i
n
a
l
s
t
o
i
n
h
i
b
i
t
o
r
y
i
n
t
e
r
n
e
u
r
o
n
s
h
a
s
b
e
e
n
q
u
i
t
e
d
i
f
f
e
r
e
n
t
f
o
r
e
a
c
h
i
n
v
e
s
t
i
g
a
t
o
r
a
n
d
e
a
c
h
e
x
p
e
r
i
m
e
n
t
a
l
a
n
i
m
a
.
Thus
l
,
t
h
e
u
l
t
r
a
s
t
r
u
c
t
u
r
a
l
r
e
l
a
t
i
o
n
s
h
i
p
s
b
e
t
w
e
e
n
C
-
t
e
r
m
i
n
a
l
s
a
n
d
i
n
h
i
b
i
t
o
r
y
i
n
t
e
r
n
e
u
r
o
n
s
a
r
e
r
e
e
x
a
m
i
n
e
d
The synaptic s汀ucturein pain modulation 3
b
a
s
e
d
on p
r
e
v
i
o
u
s
r
e
p
o
r
t
s
.
An
a
n
a
t
o
m
i
c
a
l
b
a
s
i
s
u
n
d
e
r
l
y
i
n
g
p
a
i
n
m
o
d
u
l
a
t
i
o
n
i
n
t
h
e
s
u
p
e
r
f
i
c
i
a
l
d
o
r
s
a
l
hom i
s
a
f
u
n
d
a
m
e
n
t
a
l
i
m
p
o
r
t
a
n
c
e
f
o
r
u
n
d
e
r
s
t
a
n
d
i
n
g
t
h
e
c
o
m
p
l
i
c
剖e
di
s
s
u
e
o
f
p
a
i
n
t
r
a
n
s
m
i
s
s
i
o
n
.
S
u
b
s
t
a
n
t
i
a
g
e
l
a
t
i
n
o
s
a
(SG o
r
R
o
l
a
n
d
o
s
u
b
s
t
a
n
c
e
)
i
s
a k
e
y
a
r
e
a
w
i
t
h
a
n
a
t
o
m
i
c
a
l
,
c
h
e
m
i
c
a
l
a
n
d
p
h
y
s
i
o
l
o
g
i
c
a
l
p
r
o
p
e
r
t
i
e
s
,
t
h
e
r
e
b
y
f
u
n
c
t
i
o
n
i
n
g
a
s
a
f
i
l
t
e
r
i
n
n
o
c
i
c
e
p
t
i
v
e
i
n
f
o
r
m
a
t
i
o
n
[
8
4
]
.
T
h
e
r
e
f
o
r
e
,
a
b
r
i
e
f
d
e
s
c
r
i
p
t
i
o
n
o
f
t
h
e
a
n
a
t
o
m
i
c
a
l
s
t
r
u
c
t
u
r
e
s
o
f
t
h
e
SG
i
s
h
e
l
p
f
u
l
.
I
n
t
e
r
n
e
u
r
o
n
s
i
n
t
h
e
s
u
p
e
r
f
i
c
i
a
l
s
p
i
n
a
l
d
o
r
s
a
l
horn
The c
剖s
p
i
n
a
ld
o
r
s
a
l
hom was c
l
a
s
s
i
f
i
e
d
i
n
t
o
6
r
e
g
i
o
n
s
(
l
a
y
e
r
s
)
a
c
c
o
r
d
i
n
g
t
o
t
h
e
s
h
a
p
e
,
s
i
z
e
a
n
d
t
h
e
d
e
n
s
i
t
y
o
f
n
e
r
v
e
c
e
l
l
s
by Rexed [
6
4
]
.
I
n
t
h
i
s
s
e
c
t
i
o
n
,
t
h
e
a
r
c
h
i
t
e
c
t
u
r
e
o
f
t
h
e
d
o
r
s
a
l
hom i
s
b
r
i
e
f
l
y
n
o
t
e
d
b
a
s
e
d
on t
h
e
t
h
r
e
e
p
r
e
v
i
o
u
s
m
o
n
o
g
r
a
p
h
s
[
1
2
,
1
3
,
8
7
]
.
G
e
n
e
r
a
l
l
y
,
t
h
e
s
u
p
e
r
f
i
c
i
a
l
d
o
r
s
a
l
hom c
o
n
t
a
i
n
s
l
a
m
i
n
a
1
(
m
a
r
g
i
n
a
l
z
o
n
e
)
,
l
a
m
i
n
a
1
1
(
s
u
b
s
t
a
n
t
i
a
g
e
l
a
t
i
n
o
s
a
)
and l
a
m
i
n
a
1
1
1
.
T
h
e
i
r
b
o
u
n
d
a
r
i
e
s
a
r
e
n
o
t
n
e
c
e
s
s
a
r
i
l
y
c
l
e
a
r
.
B
u
t
t
h
e
t
r
a
n
s
l
u
c
e
n
t
a
p
p
e
a
r
a
n
c
e
o
f
t
h
e
l
a
m
i
n
a
1
1
when u
n
f
i
x
e
d
s
p
i
n
a
l
d
o
r
s
a
l
hom i
s
o
b
s
e
r
v
e
d
by l
i
g
h
t
m
i
c
r
o
s
c
o
p
y
d
i
s
c
r
i
m
i
n
a
t
e
s
i
t
f
r
o
m
t
h
e
o
t
h
e
r
l
a
y
e
r
s
.
S
i
n
c
e
C
a
j
a
l
'
s
o
b
s
e
r
v
a
t
i
o
n
,
l
a
m
i
n
a
1
1
i
s
d
i
v
i
d
e
d
i
n
t
o
a
t
h
i
n
o
u
t
e
r
a
n
d
a
b
r
o
a
d
i
n
n
e
r
(
v
e
n
t
r
a
l
)
z
o
n
e
[
6
4
]
.
W
h
i
l
e
t
h
e
o
u
t
e
r
l
a
m
i
n
a
1
1
(
1
1
0
)
i
s
f
u
l
l
o
f
s
m
a
l
l
e
r
c
e
l
l
s
a
n
d
u
n
m
y
e
l
i
n
a
t
e
d
C f
i
b
e
r
s
,
t
h
e
i
n
n
e
r
l
a
m
i
n
a
1
1
(lIi
)
i
n
c
l
u
d
e
s
b
o
t
h
u
n
m
y
e
l
i
n
a
t
e
d
a
n
d
s
m
a
l
l
m
y
e
l
i
n
瓜e
df
i
b
e
r
e
n
d
i
n
g
s
d
e
m
o
n
s
t
r
a
t
e
d
by e
l
e
c
t
r
o
n
m
i
c
r
o
s
c
o
p
i
c
a
n
d
G
o
l
g
i
s
t
a
i
n
i
g
m
e
t
h
o
d
s
[
1
3
]
.
Thus
,
t
h
e
a
b
o
v
e
a
n
a
t
o
m
i
c
a
l
e
v
i
d
e
n
c
e
w
e
l
l
c
o
i
n
c
i
d
e
s
w
i
t
h
t
h
e
f
a
c
t
t
h
a
t
t
h
e
n
o
c
i
c
e
p
t
i
v
e
i
n
f
o
r
m
a
t
i
o
n
f
r
o
m
t
h
e
p
e
r
i
p
h
e
r
y
c
o
n
v
e
y
e
d
t
h
r
o
u
g
h
s
m
a
l
l
p
r
i
m
卸"ya
f
f
e
r
e
n
t
n
e
u
r
o
n
s
r
e
a
c
h
e
s
t
h
e
s
p
i
n
a
l
o
r
t
r
i
g
e
m
i
n
a
l
s
u
p
e
r
f
i
c
i
a
l
d
o
r
s
a
l
hom
,
e
s
p
e
c
i
a
l
l
y
l
a
y
e
r
1
1
,
a
n
d
t
h
e
n
o
c
i
c
e
p
t
i
v
e
i
n
p
u
t
i
s
b
e
l
i
e
v
e
d
t
o
b
e
f
i
r
s
t
m
o
d
u
l
a
t
e
d
t
h
e
r
e
.
A
l
t
h
o
u
g
h
t
h
e
r
e
may b
e
some p
r
o
b
l
e
m
s
s
i
m
p
l
y
c
l
a
s
s
i
命i
n
gi
n
t
o
c
e
l
l
t
y
p
e
s
i
n
l
a
m
i
n
a
1
1
w
i
t
h
d
e
n
d
r
i
t
i
c
mo
叩h
o
l
o
g
y
,
t
h
e
m
o
s
t
c
u
r
r
e
n
t
c
r
i
t
e
r
i
o
n
o
f
t
h
e
c
e
l
l
t
y
p
e
b
a
s
e
d
on t
h
e
c
o
n
c
i
s
e
r
e
v
i
e
w
s
[
1
2
,
8
7
]
i
s
c
o
n
v
e
n
i
e
n
t
f
o
r
t
h
e
l
a
t
e
r
d
e
s
c
r
i
p
t
i
o
n
(
F
i
g
.
1
)
.
T
h
e
r
e
a
r
e
two main c
e
l
l
t
y
p
e
s
i
n
t
h
e
l
a
m
i
n
a
1
1
;
o
n
e
i
s
n
e
w
l
y
t
e
r
m
e
d
ω
G
o
b
e
l
'
s
s
t
a
l
k
e
d
c
e
l
l
s
(
o
l
d
n
a
m
e
:
C
a
j
a
l
'
s
l
i
m
i
t
i
n
g
c
e
l
l
s
)
a
n
d
t
h
e
o
t
h
e
r
G
o
b
e
l
'
s
i
s
l
e
t
c
e
l
l
s
(
o
l
d
n
a
m
e
:
C
a
j
a
l
'
s
c
e
n
t
r
a
l
c
e
l
l
s
)
,
s
l
i
g
h
t
l
y
s
m
a
l
l
e
r
(
7
-
1
4
~mi
n
d
i
a
.
)
t
h
a
n
t
h
e
f
o
r
m
e
r
w
i
t
h
s
c
a
n
t
y
c
y
t
o
p
l
a
s
m
.
The s
t
a
l
k
e
d
c
e
l
l
s
,
c
h
a
r
a
c
t
e
r
i
s
t
i
c
a
l
l
y
w
i
t
h
s
h
o
r
t
s
t
a
l
k
-
l
i
k
e
s
p
i
n
e
s
,
a
r
e
l
o
c
a
l
i
z
e
d
i
n
o
u
t
e
r
l
a
m
i
n
a
1
1
(
1
1
0
)
.
T
h
i
s
t
y
p
e
of
c
e
l
l
s
s
e
n
d
a
x
o
n
s
i
n
t
o
l
a
m
i
n
a
1
,
t
h
u
s
c
a
l
l
e
d
i
n
t
e
r
l
a
m
i
n
a
r
i
n
t
e
m
e
u
r
o
n
s
.
They a
r
e
p
r
e
s
u
m
e
d
t
o
b
e
d
r
i
v
e
n
by o
n
l
y
n
o
x
i
o
u
s
s
t
i
m
u
l
u
s
(
n
o
c
i
c
e
p
t
i
v
e
s
p
e
c
i
f
i
c
)
o
r
by
b
o
t
h
n
o
x
i
o
u
s
a
n
d
i
n
n
o
c
u
o
u
s
s
t
i
m
u
l
i
(
w
i
d
e
d
y
n
a
m
i
c
r
a
n
g
e
:
WDR) [
1
2
]
.
The
i
s
l
e
t
c
e
l
l
s
r
o
s
t
r
o
c
a
u
d
a
l
l
y
p
r
o
j
e
c
t
d
e
n
d
r
i
t
i
c
t
r
e
e
s
t
h
r
o
u
g
h
o
u
t
t
h
e
l
a
m
i
n
a
1
1
(
8
0
・150μm i
n
d
e
p
t
h
)
.
The d
e
n
d
r
i
t
e
s
of i
s
l
e
t
c
e
l
l
s
i
n
l
a
m
i
n
a
1
1
0
a
r
e
t
h
o
u
g
h
t
t
o
b
e
n
o
c
i
c
e
p
t
i
v
e
s
p
e
c
i
f
i
c
(
low
t
h
r
e
s
h
o
l
d
:
L
T
)
,
w
h
e
r
e
a
s
t
h
o
s
e
i
n
i
n
n
e
r
l
a
m
i
n
a
1
1
(I1i
)
a
r
e
m
e
c
h
a
n
o
r
e
c
e
p
t
i
v
e
.
T
h
e
s
e
d
e
n
d
r
i
t
e
s
make s
y
n
a
p
s
e
s
w
i
t
h
o
t
h
e
r
d
e
n
d
r
i
t
e
s
a
n
d
a
x
o
n
a
l
t
e
r
m
i
n
a
l
s
.
The
似o
n
sof i
s
l
e
t
c
e
l
l
s
,
c
o
r
r
e
s
p
o
n
d
i
n
g
t
o
G
o
l
g
i
t
y
p
e
1
1
c
e
l
l
s
,
紅e
出o
u
g
h
tt
o
e
n
d
m
a
i
n
l
y
i
n
l
a
m
i
n
a
1
1
.
Fu
吋l
e
r
,
t
h
e
y
a
r
e
s
u
g
g
e
s
t
e
d
t
o
b
e
i
n
h
i
b
i
t
o
r
y
4 AkioHiura Figure 1.Schematic drawing of the central terminations of the large A type (A) and small B type (B) dorsal root ganglion neurons, and intrinsic neurons within the superficial dorsal hom. The fine nerve fibers (C・type)terminate in or near the superficial dorsal hom. DRG: dorsal root ganglion, 1: islet cells (Cajal's central cells), M: marginal cell in lamina1 (1),S: stalked cell in outer lamina11 (110). intemeurons. Gobel et al. [26] reported the ultrastructures of islet and stalked cell processes in the
1
1
0
of the c剖 lumbarspinal dorsal hom by horseradish peroxidase (HRP) labeling method. The dendritic shafts and their spine heads of islet cells make asymmetric (postsynaptic) contacts with scalloped endings of the primary at
I
erents [26]. They suggested th剖isletcells are GABAergic due to the similar morphology of the dendrites with GABAergic processes [26].Ot
her cell types (arboreal cells, II-III border cells, and spiny cells)訂ereported, but precise descriptions ofthese cells is not necessary in this chapter.The projection ofaxons of some SG cells via
L
i
ssauer' s tract through several segments and the cells in SG projecting to deeper laminae are confirmed [13]. In contrast,
SG cells receive extensive dendrites from the cells in deeper laminae [87]. Moreover,
an inhibitory descending pathway合om supraspinal nuclei (ros仕al ventromedial medulla: nucleus raphe magnus) through the dorsolateral funiculus on the SG is stated [20]. Thus,
it must be noted th剖theSG is not a closed system [87].Chemical compounds found i
n
t
h
e
s
u
b
s
t
a
n
t
i
a
g
e
l
a
t
i
n
o
s
a
Chemical substances present in the SG are classified into main three sources; one originates from small primary afferent neurons
,
the second is synthesized within neurons in the SG (intrinsic SG cells),
and the third is of supraspinal origin.While compounds originating in the SG are seen in intrinsic cells and their processes,
the otherれNOare se(!s in the terminals in the SG. Many compounds presumably participating in nociception in the SG of the spinal dorsal hom and spinal trigeminal nucleus (medulla) are summarized inThe synaptic structure in pain modulation 5 Table 1; that is
,
acetylcholinesterase (AChE),
choline acetyltransferase ChA
T),
dynorphin,
enkephalin,
y-副ninobutyricacid (GABA),
glutamate (glutamic acid),
asparate,
galanin,
neurotensin,
neuropeptide Y,
serotonin (5・HT),
ωmatostat,
加
subs阻n∞
P(SP),
thyrotropin-relasing honnone (TRH),
組
dvぉ0配tive intestinal polypeptide (VIP) [87]. In addition,
cholecystokinin [24],
methionine -enkaphalin [24],
oxytocin [24],
neurophysin [24],
adrenocorticotropin [24],
avian pancre剖icpolypeptide [41],
leucine-enkephalin [73],
calcitonin gene -related peptide (CGRP) [21,
23,
4
3,
75,
82,
86],
fluoride-resistant acid phosphatぉe (FRAP) [45],
nicotinamide adenine dinucIeotide phosphate diaphorase (NADPH・d,
an enzyme identical to nitric oxide synthase,
NOS)[
7
1],
calcium binding proteins calbindin-D28K加dcalretinin [1,
71],
isolectin B4 (IB4) [6,
55,
77],
nerve growth factor (NGF) receptor tyrosine kinase (TrkA) [55],
glial cell line司derivedneurotrophic factor
,
GDNF receptor kinase (Ret) [55],
A TP-gated receptor (P2X3) [27]
,
vanilloid receptor (capsaicin receptor: VR1: TRPV1) [11,
27],
vanilloid receptor like-l (VRL1: TRPV2) [48],
glycine [62],
加dglut創natereceptors [51
,
81,
89]. Thus,
the presence ofnumerous compounds in the SG reflects the complicated nociceptive transmission and modulation. Table 1. Chemical compounds putatively participating in nociceptive transmission identified in SG and primary sensoηneurons. DRG substantia gelatinosa (SG) Compounds orTG nerve fibers References cells cells or terminals SP•
•
•
73,
86,
87 CGRP•
•
43,
86 VIP•
87 CCK•
•
87 OXY•
24 NP•
24 peptides ACTH•
24 APP•
•
87 GAL•
•
87 NT•
•
87 NPY•
87 SOM•
•
•
41,
87 TRH•
•
87 ι6 Table 1.Continued ENK opioid L-ENK peptides M-ENK DYN lectin IB4 GABA amino acids GLU and their *5-HT derivatives GLY HIS catechol *DOP amme *NA Ca-binding CB protein CAL FRAP enz戸nes NADPH-d AChE(ChAT) glutamate NMDA・type receptors GluRI-4(AMPA) GluR5・7(kainate) TrKA other Ret receptors P2X3 VRl VRLl * supraspinal origin