Download The spinothalamic tract: An examination of the cells of origin of the

THE JOURNAL OF COMPARATIVE NEUROLOGY 260:349-361(1987)
The Spinothalamic Tract:
An Examination of the Cells of Origin of the Dorsolateral
and Ventral Spinothalamic Pathways in Cats
M.W. JONES, A.V. APKARIAN, R.T. STEVENS AND C.J. HODGE, JR.
Department of Neurosurgery, State University of New York Health Science Center,
Syracuse, New York 13210
ABSTRACT
The locations of spinothalamic neurons and the funicular trajectories of
their axons were studied in cats by retrograde transport of horseradish
peroxidase (HRP). Five animals were used as controls to determine the
cervical and lumbar laminar distributions of neurons contributing to the
spinothalamic tract. An additional eight animals were used to determine
the funicular trajectories of the spinothalamic axons of lumbar neurons by
utilizing a series of thoracic spinal cord lesions in conjunction with retrograde transport of HRP from the sensory thalamus. Three of these animals
underwent midthoracic ventral quadrant lesions, four animals underwent
midthoracic dorsolateral funiculus lesions, and one animal underwent total
spinal cord transection sparing the dorsal columns. The locations of the cells
containing the HRP reaction product were then determined after a 3- to 5day survival time, and the patterns of labeled cell locations of the lesion
groups were compared to the control group patterns. In the lesioned animals,
the cervical spinothalamic cell locations were used as a control to confirm
the uniformity of the injection sites, transport and tissue processing.
The major finding of this study is that there exist two distinct components of the spinothalamic tract. The dorsolateral spinothalamic tract (DSTT)
is made up of axons originating in contralateral spinal cord lamina I and
has negligible contribution from the deeper spinal cord laminae. The axons
of lamina I cells cross segmentally and ascend exclusively in the dorsolateral
funiculus (DLF). The DSTT comprises approximately 25% of the totaI spinothalamic input from the lumbar enlargement. The ventral spinothalamic
tract (VSTT) is made up of axons originating in spinal cord laminae IV-V
and VII-X. Very few lamina I cells contribute axons to the VSTT. This
crossed pathway ascends in the ventrolateral and ventromedial portions of
the spinal cord. No cells contributing to the spinothalamic tract were identified in spinal cord segments caudal to a dorsal column sparing lesion,
indicating that there are no spinothalamic tract axons traveling in the
dorsal columns.
These results expand the classical concept of information processing by
the spinothalamic tract. The DSTT is made up of lamina I cell axons. All
lamina I spinothalamic cells respond exclusively to noxious peripheral stimuli. Hence the DSTT is a major nociceptive-specific ascending spinal pathway, yet lies outside the confines normally assigned to the spinothalamic
tract. In contrast, the spinothalamic tract axons ascending in the traditional
ventral location originate predominantly from neurons of wide dynamic
range as well as from low-threshold neurons. These findings have novel
implications concerning the relative importance, for nociception, of lamina I
and deeper laminar input to the thalamus.
Key words: thalamus, spinal pathways, horseradish peroxidase, dorsolateral
funiculus, ventral funiculi
0 1987 ALAN R. LISS, INC.
Accepted November 12, 1986.
M.W. JONES ET AL.
350
The spinothalamic tract, an important nociceptive system
in mammals, has been thought to be confined to the ventral
quadrant of the spinal cord since its original description by
Edinger (1889). This viewpoint has been supported by the
clinical success of ventrolateral cordotomy for pain relief
(Horrax, '29; Voris, '57; Rosomoff et al., '65; White et al.,
'50), identification of thalamic terminal degeneration following ventral quadrant spinal cord section (Berkley, '80;
Boivie, '71, '791, and anatomic and physiologic identification of ventral quadrant axons that project to the thalamus
(Applebaum et al., '75; Willis et al., '79; Giesler et al., '81a).
The cells of origin of the spinothalamic pathway are found
in three different spinal cord locations: the apex of the
dorsal horn (lamina I), the deep dorsal horn (laminae IvVI), and the ventral horn (laminae VII, VIII, and XI. The
relative contributions of these three areas to the spinothalamic tract varies between species (Trevino et al., '72, '73;
Albe-Fessard et al., '74; Trevino and Carstens, '75). The
lamina I contribution to the spinothalamic tract (Foerster
and Gagel, '32; Kuru, '38; Morin et al., '51; Dilly et al., '68;
Trevino et al., '73; Willis et al., '74; Albe-Fessard et al., '75;
Trevino and Carstens, '75; Giesler et al., '76; Willis et al.,
'78a; Chung et al., '79; Giesler et al., '79; Kenshalo et al.,
'79; Willis et al., '79; Hayes and Rustioni, '80; Craig and
Burton, '81; Kevetter and Willis, '83, '84; Craig and Kniffki,
'84; Hylden et al., '85; Granum, '86) is of particular significance, since lamina I contains a major spinal cord concentration of nociceptive-specific cells (Christensen and Perl,
'70; Price and Mayer, '75; Kumazawa et al., '75; Kumazawa
and Perl, '78; Cervero et al., '79; Fitzgerald and Wall, '80).
Since the majority of lamina I cells that project rostrally
are located in the contralateral dorsolateral funiculus (Zemlan et al., '78; Molenaar and Kuypers, '78; McMahon and
Wall, '83, '85; Apkarian et al., '851, some authors have
questioned the importance of their contribution to the spinothalamic system (Molenaar and Kuypers, '78; McMahon
and Wall, '83). Preliminary experiments conducted in our
laboratory have clearly shown, however, that in cats, some
of the lamina I cell axons that ascend in the dorsolateral
funiculus terminate in the thalamus (Jones et al., '85).
Therefore there are, in cats, two separate spinothalamic
pathways; a ventral spinothalamic tract (VSTT),including
both the ventrolateral and ventromedial pathways, and a
dorsolateral spinothalamic tract (DSTT) made up primarily
of lamina I cell axons. On the basis of our preliminary
experiments (Jones et al., '85) it was unclear whether the
axons of all contralaterally projecting spinothalamic lamina I cells ascend in the dorsolateral funiculus (DLF) or
whether there is a distribution of these axons between the
ventral and dorsal spinothalamic pathways.
The purpose of this study was to investigate the spinothalamic tract of cats. In particular, the relative contributions
of the lumbar spinal cord laminae to the DSTT and to the
VSTT were determined and compared to the total population of neurons whose axons make up the lumbar portion of
the spinothalamic tract. Retrograde transport of horseradish peroxidase (HRP) from the thalamus to the cervical and
lumbar spinal cords was combined with a variety of midthoracic spinal cord lesions to investigate this question.
METHODS
procedures. HRP conjugated to wheatgerm agglutinin
(WGA-HRP, n = 20) or HRP-Sigma VI (n = 2) was used as
the neural tracer.
A total of 1 pl of 2% WGA-HRP in 0.2 M mannose and
0.9% saline or 1 pl of 50% HRP-Sigma VI in 0.9% saline
was injected stereotactically into the somatosensory thalamus. In accordance with known spinothalamic termination
sites (Boivie, '71, '79; Applebaum et al., '79; Berkley, '80;
Craig and Burton, '85; Apkarian et al., '87), three to five
injections were made in each animal to include the ventral
posterior lateral nucleus (VPL), the ventral lateral nucleus
(VL), the central lateral nucleus (CL), the posterior group
(PO) and the nucleus submedius (SM). The stereotactic coordinates for these injections were determined from standard atlases (Jasper and Ajmone-Marsan, '54; Berman and
Jones, '82). The WGA-HRP was injected with a 1-pl Hamilton syringe a t a rate of 0.02 pl/min beginning 5 min after
initial needle placement. The needle was not removed for
5-10 min after completing the injection to reduce the spread
of HRP along the needle track.
Some animals, at the time of injection, also underwent
thoracic laminectomy (Tll-T12),through which spinal cord
lesions were made by microsurgical technique. The lesions
included ventral quadrant (VQ) section ipsilateral to the
thalamic injection, dorsolateral funiculus section ipsilatera1 to the thalamic injection, and a spinal cord transection
sparing the dorsal columns.
After a 3-to 5-day survival time, animals were anesthetized with Nembutal (40 mgkg), pretreated with intravenous heparin, and perfused transcardially with 0.9% saline
(1.0 liter) and then by 1.25% glutaraldehyde and 1%paraformaldehyde in 0.1 M phosphate buffer at pH 7.4 (2.0 liters
at room temperature for 30 min). This was followed by 1.0
liter of 5% sucrose in the same buffer a t 4°C. The tissue
was removed and refrigerated overnight in a 5% buffered
sucrose solution. The diencephalon was sectioned coronally
(60-80 pm) from the level of the anterior commissure to the
inferior colliculus to include rostra1 midbrain structures.
Representative transverse sections were collected from the
brainstem and the first cervical segment to include the
dorsal column nuclei and the lateral cervical nucleus.
Transverse sections were collected from the lumbar (L5-Sl)
and cervical (C6-Tl) enlargements. The cervical enlargement sections were collected to determine the consistency
of the pattern of transport from animal to animal.
Tissue sections were processed for HRP histochemistry
by using tetramethyl benzidine as the chromagen (Mesulam, '78) and lightly counterstained with 1%neutral red.
The thalamic injection sites and the extent of the spinal
cord lesions were reconstructed by means of Nissl-stained
(5% cresyl violet) sections.
Cells within the spinal gray matter that demonstrated
the distinct stippling characteristic of HRP label were
counted and their locations were mapped from the transverse sections by brightfield and darkfield microscopy. Cell
locations were characterized according to the laminar
scheme of Rexed ('54).
RESULTS
Thalamic injection sites
Twenty-two cats underwent multiple thalamic HRP injecTwenty-two adult domestic cats were used for these ex- tions, some in combination with various thoracic spinal
periments. Nembutal anesthesia (35 mgkg), sterile sur- white matter lesions. Since many spinal cord neurons projgical technique, and antibiotic prophylaxis were used in ali ect directly to the midbrain (Trevino, '76; Willis et al., '79;
SPINOTHALAMIC TRACT
351
Control
VQ Lesion
3
4
4
Fig. 2. Drawings of thalamic injection sites in four cats with thoracic VQ
lesions ipsilateral to the injection site (VQ lesions 1,2, 3,and 4).
5
Mantyh, '82; Wiberg and Blomqvist, '84; McMahon and
Wall, '85),only those animals in which the injection did not
spread to the midbrain were included in the data analysis.
In addition, the targeted thalamic nuclei (VPL, PO, CL,
SM), which are those with known STT terminations, had to
be well filled. Thirteen of these animals had HRP injections
Fig. 1. Representative drawings of the extents of thalamic injection sites that included the targeted sensory thalamic nuclei and did
at the level of VPL and PO in cats with no spinal cord lesions (Controls 1, not impinge upon midbrain structures. Only these 13 ani2, 3, 4, and 5). The needle tracts are represented by blackened area. The
dark portion of the injection site, as seen after TMB processing, is stippled. mals were used for data analysis. The extents of the HRP
injection sites are shown in Figures 1-3 for all 13 cats. Each
The drawings and nomenclature were adapted from Jasper ('54).
drawing in these figures is a compilation of multiple diencephalic sections through the injected region, illustrating
the maximum extent of the HRP injection. A photomicroAbbreviations
graph of a sample section from which these drawings were
obtained is shown in Figure 4. The injection sites were
CL
centrolateral n.
LGN
lateral geniculate n.
subdivided into a central dark, concentrated portion that
MD
medial dorsal n.
surrounded the point of injection and an adjacent region of
PO1
posterior n, lateral division
lighter label. Figures 1-3 show the dark portion of the
PO,,,
posterior n., medial division
injection at the level of the body of VPL and at the level of
PUL
pulvinar
SM
n. submedius
PO. In these animals the dark portion of the injection
VL
ventral lateral n.
covered most of the somatosensory thalamus and was conVPL
ventral posterior lateral n.
sidered to be the primary region of HRP uptake (Kim and
VPM ventral posterior medial n.
M.W. JONES ET AL.
352
DLF Lesion
dorsal to the cortex along the needle track. The injection
site occasionally included a portion of the contralateral
intralaminar nuclei.
Unlesioned animals
Dorsal Column Sparing
Fig. 3. Drawings of thalamic injection sites in three cats with thoracic
DLF lesions ipsilateral to the injection site (DLF lesions 1, 2, and 3) and in
one cat with a lesion sparing the dorsal columns.
Strick, '76; Mesulam and Rosene, '79). Table 1indicates the
intensity of injected HRP in the targeted somatosensory
thalamic nuclei for all 13 animals. While all the injections
included the lateral somatosensory thalamus, there are
nonetheless variations in the placements and the extents of
the injections (Figs. 1-3). The most significant difference is
that some of the iniections include most or all of PO,
whereas other injections are much less dense in the PO
region. When the caudal portion of the injection spread
densely into PO, there were significantly more labeled cells
per section in the cervical enlargement (Mann-Whitney U
test, heavily injected versus lightly and uninjected PO from
Table 1:PG0.028).
Outside the confines of the thalamus, the rostra1 extension of the injection site often included the caudate nucleus,
and laterally the injections occasionally impinged upon the
internal capsule. There was occasional light HRP spread
Cats with unilateral thalamic injections and no spinal
cord lesion served to identify the lumbar and cervical cells
of origin of the total spinothalamic tract (VSW and DSTT).
WGA-HRP was used in three experiments (Controls 1, 2,
and 31, whereas HRP-Sigma VI was used in two experiments (Controls 4 and 5). The distribution of label was
examined in the cervical and lumbar enlargements. Labeled cells, found contralateral to the thalamic injection
site, were located mainly in lamina I, laminae IV and V,
the medial aspect of lamina VII, and lamina VIII. Occasionally a few HRP-labeled neurons were found within the
substantia gelatinosa. Ipsilateral to the injection site a
small number of cells were located in lateral lamina I just
medial to the dorsal root entry zone and in the medial
aspect of Iamina VII. The percentage of labeled ipsilateral
cells varied from 5% to 10% of the total labeled cells in
control experiments. The locations and density of label in
the lumbar enlargement of one experiment (Control 1)is
shown in Figure 6. In all control experiments the numbers
of labeled cells in the cervical enlargement were similar to
those in the lumbar enlargement. A larger percentage of
the labeled cells were found in laminae N - V in the cervical
spinal cord than in the lumbar spinal cord (mean of 46% vs.
mean of 21%; Table 2). In HRP-Sigma VI control experiments the number of HRP-labeled cells located within the
nucleus proprius of the lumbar enlargement was smaller
than the number found in WGA-HRP experiments. However, this difference was statistically insignificant (MannWhitney U test).
The percentage of labeled lamina I cells in the lumbar
enlargement varied from 14% to 30% of the total labeled
cells. The density of the lamina I projection can be observed
in horizontal sections (Fig. 9B). Labeled lamina I neurons
often occurred in clusters of three to six cells just medial to
the dorsal root entry zone (Fig. 9A). Many labeled lamina I
neurons were oriented longitudinally (Fig. 9C). The HRPlabeled cells in the deeper laminae were polygonal or flattened and appeared larger than most lamina I cells (Willis
et al., '79; Meyers and Snow, '82b). The total numbers of
HRP-labeled cells in the lumbar enlargement and in the
cervical enlargement were similar for each animal. However, there was a larger concentration of labeled neurons in
laminae VII and VIYI of the lumbar enlargement than in
the cervical enlargement (Table 2).
Control 1(Table 2), had two to four times as many labeled
cells per section as the other control experiments. Hence,
the injection coordinates, survival time (5 days), and neural
tracer (WGA-HRP) used in Control 1 were used in subsequent experiments, i n which thoracic spinal lesions were
made.
Ventral quadrant lesions
Four cats (VQ lesion 1,2,3, and 4) had adequate thalamic
WGA-HRP injections combined with ventral quadrant lesions ipsilateral to the injection side. These lesions were
designed to block HRP transport via the ventral quadrant
and thereby elucidate the cells of origin of the dorsolateral
spinothalamic projection. The number and distribution of
HRP labeled neurons in the cervical spinal cord of these
animals were similar to the data found for the control
SPINOTHALAMIC TRACT
353
Fig. 4. Photomicrograph of a representative section of the thalamic injection site from the experiment DLF lesion 1 a t the level of VPL. Two needle
tracts are visible in the tissue. Bar = 1.0 mm.
TABLE 1. Thalamic Nuclei Injected
PO
Experiment no.
Control
1
2
3
4
5
VQ lesion
**
-
**
1
Symbols: *-
=
Heavy; *
**
**
*
**
**
**
**
*
**
**
*
=
**
-
**
**
* :x
**
-
1
**
**
**
2
3
Dorsal column
spared
*
SM
**
*
*
I-i
4
DLF lesion
**
**
**
CL
**
*
**
2
3
VPL
*I
**
**
**
c
*
*
**
**
**
**
**
**
**
*
**
light; - = not injected.
The number and location of labeled neurons found in the
contralateral lumbar enlargement varied with the size and
position of the thoracic VQ lesion. In one animal (VQ lesion
1)the thoracic lesion included all of the ventral quadrant
and all but a small portion of the dorsal aspect of the
dorsolateral funiculus (Fig. 5 , VQ lesion 1).The number of
labeled cells in the contralateral lumbar enlargement was
small, indicating that the STT crosses below the level of
the lesion. The labeled neurons in this animal were located
in lamina I exclusively (Table 3, VQ lesion 1).When the
VQ lesion spared a larger portion of the dorsolateral funiculus (Fig. 5 , VQ lesions 2 and 4),a small number of labeled
cells were found in the deeper laminae (Fig. 7A; Table 3,
VQ lesions 2 and 4), yet more than 90% of the contralateral
lumbar enlargement label was still located in lamina I.
When the DLF and part of the ventral funiculus were
spared (Fig. 5 , VQ lesion 3), a n even larger proportion of
labeled cells were located in deeper laminae (Fig. 7B, Table
3, VQ lesion 3).
Dorsolateral funiculus lesions
animals. However, most of the HRP-labeled cells in the
lumbar enlargement were located in lamina I, contralateral
to the thalamic injection site (Fig. 7, Table 3). The morphology of the HRP-labeled neurons following VQ lesions was
similar to that found in the control experiments.
Three cats (DLF lesion 1, 2, and 3) had lesions of the
thoracic dorsolateral funiculus made ipsilateral to the thalamic injections. These lesions (Fig. 5 , DLF lesion) were
designed to block HRP transport through the DLF and
served to identify the cells of origin of the ventral spinothalamic projections. In these animals the cervical HRP label
M.W. JONES ET AL.
354
TABLE 2. Distribution of Contralaterally Labeled Cells in the Lumbar and Cervical Enlargements of Cats
Following a Thalamic HRP Injection and No Spinal Lesion
1
Cnntrnl
2
3
4
5
Cervical enlargement
Laminae
1-111
IV-VI
VII-x
Total cells per section
Total cells
Total sections
2.73'
4.50
1.00
0.22
0.56
0.24
0.33
1.02
0.43
1.01
0.35
0.11
0.50
0.40
0.15
8.23
246
30
1.02
55
54
1.78
91
51
1.47
58
40
1.05
21
20
Lumbar enlargement
Laminae
1-111
IV-VI
VII-x
Total cells per section
Total cells
Total sections
2.13
2.05
2.90
7.08
964
119
0.33
0.69
1.33
2.35
78
33
0.22
0.35
1.06
1.63
98
60
0.45
0.31
1.06
1.52
I2
40
0.36
0.17
1.13
1.66
60
36
Mean %
38'
46
16
21
21
58
'Average number of HRP-labeled cells per section.
'Mean percentage of labeled cells of all control experiments.
VQ Lesion
DLF Lesion
was similar to that of control animals. In the lumbar enlargement, the main HRP-labeled cell populations were
located in contralateral laminae IV-V and VII-VIII (Fig. 8,
Table 4).The distribution, number, and morphology of lumbar HRP labeled neurons in laminae IV-V and laminae
VII -VIII were similar to control characteristics. There were
very few labeled lamina I cells found contralateral to the
injection site, and HRP-labeled lamina I cells were present
ipsilaterally only when the HRP injection site extended
across the midline (Fig. 3, DLF lesion 2; Fig. 8).
Dorsal column-sparedlesion
2
Dorsal Column Spared
1
Fig. 5. Composite drawings of all thoracic spinal cord lesions. The numbers adjacent to the drawings for each paradigm correspond to the experiment numbers used in all figures and tables. The arrows indicate the
midline septum between the dorsal columns. In each drawing, the left side
is ipsilateral to the thalamic injection site.
A thoracic spinal lesion that spared only the dorsal columns and a small portion of the dorsalmost aspect of the
contralateral dorsolateral funiculus was made in one animal (Fig. 5 , Dorsal Column Spared). The dorsal columns
and their blood supply appeared intact. The injection site
included medial and lateral thalamic nuclei with minimal
spread across the midline (Fig. 3, Dorsal Column Sparing).
The number and distribution of HRP-labeled cells in the
cervical enlargement (3.95 cells per section) was similar to
findings for other cervical controls. Caudal to the lesion, in
the lumbar enlargement, there were no HRP-labeled cells,
suggesting that spinothalamic axons do not course through
the dorsal columns.
Statistical comparison between groups
The number of labeled neurons per section in the dorsal
horn of each animal was subdivided into three main groups:
laminae 1-111,laminae IV-VI, and laminae VII-X (see Tables
2-4). This grouping is intended to correspond to functionally distinct cell populations of the STT (see below for evidence and references), and is also designed to minimize
variations due to erroneous placement of some labeled neurons into specific laminae. The number of labeled neurons
in laminae 11,111, IX, and X were very small and make a
minimal contribution to the values shown in Tables 2-4.
The ipsilateral STT was not studied statistically, since the
number of labeled neurons was small and highly dependent
on the degree of spread of the thalamic injection across the
3.55
SPINOTHALAMIC TRACT
TABLE 3. Distribution of Contralaterally Labeled Cells in the Lumbar and Cervical Enlargements of Cats
Followinn a Tbalamic HRP Iniection and Iosilateral Thoracic Ventral Quadrant Lesion
VQ lesion
1
2
3
4
Cervical enlargement
Laminae
1-111
IV-VI
VII-x
2.15'
1.99
1.26
2.50
4.57
1.40
1.30
1.41
0.28
0.31
0.19
0.13
5.40
216
40
8.50
340
40
2.98
119
40
0.62
72
116
0.25
0
0
0.25
18
71
1.74
0.06
0.11
1.93
222
115
1.67
0.41
0.52
2.60
208
80
0.19
0.01
0
0.20
17
84
Total cells per section
Total cells
Total sections
Lumbar enlargement
Laminae
1-111
N-VI
VII-x
Total cells per section
Total cells
Total sections
Mean %
41'
42
17
87
6
6
IAverage number of HRP labeled cells per section.
'Mean percentage of labeled cells of all VQ lesion experiments
LUMBAR CONTROL 1
119 Sections
Laminae
IPSILATERAL
CELL PLOT
CONTRALATERAL
I
zI/ In
1
Ip
[.
1
I
P
1
[I
m
I
1
PII
mn
I
I
X
100
50
0
50
100
150
200
250
(Number of Cells/Section)x 100
Fig. 6. Bar graph of the laminar distribution and plot of the position of
HRP-labeled cells in the lumbar enlargement of Control 1 ipsilateral and
contralateral to the thalamic injection. The cell plot is a compilation of
labeled cells found in 10 sections. The right side of the cell plot is contralat
era1 to the thalamic injection.
midline. Despite the dependence of the number of labeled
cells in the contralateral cervical enlargement on the inclusion of PO in the injection site, the variations in injection
sites were not associated with any change in the proportion
of labeled cells found in laminae 1-111in the contralateral
cervical enlargement (Mann-Whitney U test, P G0.45,
Tables 2-4).
A nonparametric statistical comparison (Mann-Whitney
U test) was made for each laminar grouping of the contralateral label in the cervical and lumbar enlargement between the control animals and the DLF- or VQ-lesioned
cats. The results are summarized in Table 5 . Because multiple comparisons were made with a single set of animals
as the control group, the P values reported must be considered only approximations and are included as indicators of
change rather than as precise probability measurements.
This analysis showed no significant differences ( P > 0.05)
in the number of HRP-labeledcells for each laminar grouping within the cervical dorsal horn between control and
VQ- or DLF-lesioned animals despite the variation added
by changes due to the density of PO injection. This suggests
that the thalamic HRP injections and subsequent transport
to the cervical dorsal horn were equivalent between the
groups of animals. In the lumbar enlargement, there was a
significant reduction in the number of labeled cells per
section in the deeper laminae of VQ-lesioned animals compared t o controls (laminae IV-VI, P < 0.04; laminae VII-X,
P < 0.007), and there was a significant reduction in the
number of HRP-labeled cells in the superficial laminae of
DLF-lesioned animals compared to controls (laminae 1-111,
P < 0.01). These results strongly suggest that the differences of label seen in the lumbar dorsal horn are due to the
placements of the lesions in the thoracic spinal white
matter.
M.W. JONES ET AL.
356
LUMBAR (Thoracic VQ Lesion 2 )
A.
LESION
CELL PLOT
115 Sections
Lammoe
1
I
1
c1
[:
E
I
I
l
C
I
1
3
1
I
I
1
1
250
LUMBAR (Thoracic VQ Lesion 3)
B.
LESION
CELL PLOT
80 Sections
IPSILATERAL
CONTRALATERAL
Laminae
I
nm
1p
P
a=/
I
100
50
0
50
100
150
200
250
(Number of Cells/Section) x 100
Fig. 7. Bar graphs of laminar distributions and plots of positions of HRP- The ipsilateral VQ lesion at the midthoracic level is indicated in black for
labeled cells in two ventral quadrant-lesioned animals (VQ lesions 2 and 3). both aninals. The cell plots are a compilation of 10 lumbar enlargement
Ipsilateral and contralateral are in reference to the thalamic injection side. sections. Left is ipsilateral to the injection.
dorsolateral projection originates predominantly in spinal
cord lamina I in contrast to the ventral projections, which
In these experiments the maximum size of the total spi- originate mainly from cell populations in laminae IV and
nothalamic cell population was up to 7 cells per section in V and in VII and VIII.
the lumbar enlargement and 8.5 cells per section in the
Technical considerations
cervical enlargement. The dorsolateral spinothalamic projection is approximately one fourth the size of this total
Several technical considerations are germane to the respinothalamic projection. The ventral spinothalamic path- sults of this study. Recent investigations (Gerfen et al., '82;
way is three fourths the size of the total spinothalamic Itaya and Van Hoesen, '82; Itoh et al., '84; Harrison et al.,
tract. These estimates are based on a comparision of the '84; Hultborn and Storai, '84) described transneuronal
number of labeled cells per section in lumbar cord in a transport of WGA-HRP. However, transneuronal transport
control experiment (Table 2, Control 1)with the number in in the long tracts of the spinal cord has been described only
an animal with a ventral quadrant lesion (Table 3, VQ in the anterograde direction (Peschanski and Ralston, '85).
lesion 2; 1.9 cells per section), and the number in a n animal In the present study the dorsal column nuclei were reguwith a dorsolateral funiculus lesion (Table 4, DLF lesion 2; larly examined and cellular label was invariably found, but
6.0 cells per section). These three animals had similar injec- labeled fibers were very rarely found in the dorsal columns
tions, similar cervical labeling, and appropriate thoracic of the spinal cord, indicating that significant transsynaptic
lesions. Since it is unclear whether the small number of retrograde transport was not occurring in these long tracts
lamina I axons ascending in the VSTT and the small num- (Jones et al., '85). In experiments using HRP-Sigma VI,
ber of axons of deeper laminae ascending in the DSTT which has not been demonstrated to undergo transsynaptic
represent the only output of the parent cells or represent transport, the major spinothalamic cell populations were
collateral branches, it is possible that a single spinal cord similar to those of WGA-HRP experiments. Recent studies
neuron could contribute to both pathways.
in our laboratory, using retrogradely transported fluorescent dyes in conjunction with ventral quadrant lesions of
DISCUSSION
the thoracic spinal cord, also demonstrated the existence of
The results of this study show the existence of predomi- a lamina I DSTT whose cells of origin are similar in numnantly crossed spinothalamic pathways that ascend through bers and positions to these HRP experiments (Stevens et
the DLF and VQ in cats. The cell populations that contrib- al., '85). Whereas transsynaptic transport cannot be comute to each pathway are distinct from one another. The pletely excluded as a contributor to the results, it is doubt-
Relative sizes of the spinothalamic projections
357
SPINOTHALAMIC TRACT
IPSILATERAL
CELL PLOT
LESION
LUMBAR (Thoracic DLF Lesion 2 )
80 Sections
CONTRALATERAL
Laminae
I
U/Ul
Is!
P
PI
pn
mn
X
I
I
100
50
0
I
I
1
I
1
50
100
150
200
250
(Number of Cells/Section) x 100
Fig. 8. Bar graph of laminar distribution and plot of positions of HRPlabeled cells in a n animal with a dorsolateral funiculus lesion (DLF lesion
2). Ipsilateral and contralateral are in reference to the thalamic injection
side. The ipsilateral DLF lesion a t the midthoracic level is shown in black.
The cell plot is a compilation of 10 lumbar enlargement sections. Left is
ipsilateral to the injection.
TABLE 4. Distribution of Contralaterally Labeled Cells in the Lumbar and Cervical
Enlargements of Cats Following a Thalamic HRP Injection and Ipsilateral Thoracic
Dorsolateral Funiculus Lesion
DLF lesion
Cervical enlargement
Laminae
1-111
IV-VI
VII-x
Total cells per section
Total cells
Total sections
Lumbar enlargement
Laminae
1-111
IV-VI
VII-x
Total cells per section
Total cells
Total sections
1
2
3
Mean %
1.091
2.21
0.81
4.20
337
80
2.28
3.43
0.93
6.63
265
40
0.43
0.88
0.32
1.63
46
28
292
53
18
0.15
0.35
0.73
1.22
88
72
0.12
1.98
3.93
6.03
479
80
0.01
0.06
0.15
6
29
64
0.22
18
80
'Average number of HRP labeled cells per section.
'Mean percent of labeled cells of all DLF lesion experiments.
ful that it makes a significant contribution to cell labeling
in these experiments. The uptake of HRP by fibers of passage in the corona radiata damaged by the injection needle
does not present a problem in interpretation as far as spinal
labeling is concerned, since the spinothalamic tract is the
most rostra1 known efferent spinal projection. Therefore,
limiting the diencephalic injection to the thalamus, avoiding injection spread to the midbrain, and using a low concentration of WGA-HRP (2%) allow the assumption to be
made that all HRP-labeled spinal cord cells in this study
have direct thalamic projections.
The variation in the number of labeled cells per section
in the lumbar enlargement was large within a single experimental paradigm. This variation in the amount of HRP
label could be due to differences between animals or to
variability i n injection sites, axonal uptake, and tissue processing (Willis et al., '79; Granum, '86). In these experiments, the density of the injection at the level of PO was
related to the total number of cells labeled, but not to the
relative laminar distribution of the labeled cells. Since the
STT projection to PO is sparse in cats, (Boivie, '71, '79;
Applebaum el al., '79; Berkley, '80; Craig and Burton, '85;
Apkarian et al., '87) and since the PO injection does not
change the laminar pattern of label, it is likely that the
caudal injection of HRP in PO increases labeling in the
spinal cord primarily by being taken up in the damaged
STT fibers of passage rather than by the STT terminals in
the PO region. Since there was not a statistically significant difference in the cervical laminar distributions between control and DLF- or VQ-lesioned animals, it seems
unlikely that there was any systematic variation in the
degree of HRP uptake, labeling, or tissue processing between these groups.
Ascending projections to the thalamus
The relative laminar distributions of STT neurons in the
cervical enlargement of all 13 cats studied here are similar
to those reported by Carstens and Trevino ('78) for large
thalamic injections of HRP-Sigma VI. However, the total
number of labeled neurons in the present study was two to
three times larger than that reported by Carstens and
Trevino ('78). There is no obvious reason for this variation
in results, though there are clear technical differences between the studies. The locations and densities of STT cells
M.W. JONES ET AL.
358
TABLE 5. Results of Mann-Whitney U Test Between Control and DLF- or
VQ-Lesioned Animals
Cervical enlargement
Laminae
1-111
IV-VI
VII-x
Lumbar enlargement
Laminae
1-111
IV-VI
VII-x
INS
=
Control vs. VQ lesion
Control vs. DLF lesion
NS'
NS
NS
NS
NS
P < 0.04
P < 0.007
P < 0.01
NS
NS
NS
NS
P > 0.05.
lis et al., '79). Based on the control experiments in this
study, the number of STT neurons appears equally distributed between the cervical and lumbar enlargements, though
there is a greater percentage of laminae IV-V cells contributing to the STT from the cervical enlargement and a
greater percentage of laminae VII-X cells contributing to
the STT in the lumbar enlargement. The distribution of
HRP-labeled rat lumbar spinothalamic neurons in laminae
IV and V and in VII and VIII is similar to that seen in cats
and monkeys (Giesler et al., '79, '81b; Kevetter and Willis,
'83, '84; cf. Granum, '86). However, there is a prominent
projection from medial lamina VI in rats that is small in
cats and is not present in monkeys (Menetrey et al., '84). In
addition, the lamina I spinothalamic projection from the
rat lumbar enlargement is small compared to cats and
monkeys (Giesler et al., '79, '81b; Kevetter and Willis, '83;
Menetrey et al., '841, and many of the reported rat spinothalamic lamina I neurons probably terminate in the rostra1
midbrain rather than the thalamus (McMahon and Wall,
'83, '85; Granum, '86; cf. Hylden et al., '85).
Previous studies using degeneration techniques have
failed to identify a spinothalamic projection in the dorsolatera1 funiculus (Boivie, '70, '71; Nijensohn and Kerr, '75).
Based on these studies, little thought has been given to the
idea that a DSTT might exist as an additional spinal diencephalic pathway (Willis and Coggeshall, '78b). However,
with the demonstration that the majority, if not all, of
lamina I neurons that project rostrally send their axons
through the dorsolateral funiculus in rats (Zemlan et al.,
'78; McMahon and Wall, '831,cats (Apkarian et al., '85) and
monkeys (Molenaar and Kuypers, '78), the possibility of the
existence of a DSTT had to be reconsidered. The results of
this study, as well as the results of our previous report
(Jones et al., '85) clearly demonstrate the existence of a
DSTT in cats made up primarily of lamina I cell axons. The
DSTT comprises approximately 25% of the total spinothaFig. 9. Photomicrographs of HRP-labeled lamina I neurons contralateral
to the thalamic injections. A Triplet of HRP-labeled lamina I neurons lamic projection from the lumbar enlargement. This value
located just medial to dorsal root entry zone in an animal with a ventral agrees closely with previous estimates of the contribution
quadrant lesion placed ipsilateral to the thalamic injection (transverse from lamina I to the spinothalamic tract (Carstens and
section). B, C: Darkfield photomicrographs of horizontal sections of lumbar
Trevino, '78; Willis et al., '78a, '79).
spinal cord through the marginal zone of the dorsal horn showing the
The DSTT fibers are spread diffusely throughout the DLF
rostrocaudal orientation of HRP-labeled lamina I cells. Bar = 100 pm.
of the lumbar spinal cord of cats contralateral to their cells
of origin and ipsilateral to their thalamic termination sites
in the lumbar enlargements of cats used as controls are (Jones et al., '85). Similarly, labeled fibers were observed in
similar to those found in HRP studies of the macaque (Trev- the DLF at the level of the cervical enlargement ipsilateral
ino and Carstens, '75; Willis et al., '78a, '79; Hayes and to the thalamic injection (unpublished observation). This
Rustioni, '80), suggesting that the spinothalamic tracts in indicates that axons within the DSTT cross segmentally,
cats and monkevs are not as disDarate as areviouslv thought and that this pathway is present at lumbar, thoracic, and
(Trevino and Carstens, '75; Caistens an2 Trevino, '78; Wil- cervical levels.
SPINOTHALAMIC TRACT
359
range, and have small contralateral receptive fields. Therefore both nociceptive-specific and wide-dynamic-range cells
seem to contribute axons to the VSTT.
The finding that there exists a unique population of neurons in spinal cord lamina I that respond to high-threshold
mechanical stimulation and to noxious levels of cutaneous
temperature has been a n important step in unraveling the
contradictions concerning how the spinal cord signals noxious peripheral stimuli (Christensen and Perl, '70). The
demonstration that these lamina I cells contribute to the
spinothalamic tract (Willis et al., '74) seemed to provide a
clear explanation for the behavioral effects of anterolateral
cordotomy. Even more impressive, in terms of identifying a
"labeled line" for rostral transmission of information about
noxious peripheral stimuli, have been the studies demonstrating that all lamina I cells that project to the thalamus
and midbrain respond exclusively to noxious stimuli (Craig
and Kniffki, '85; Hylden et al., '85). Like the spinothalamic
cells originating in the deeper laminae of the spinal cord,
those located in lamina I project to both medial and lateral
portions of the sensory thalamus (Applebaum et al., '75,
'79; Chung et al., '79; Giesler et al., '79, '81a, '81b; Kevetter
and Willis, '83, '84; Craig and Kniffki, '85; Stevens et al.,
'85). Unique to the lamina I projection, however, is the
termination in nucleus submedius of the thalamus (Craig
and Burton, '81). The current study clearly demonstrates
that in cats a major nociceptive-specific ascending spinal
cord pathway, originating in lamina I, travels in the DLF
rather than the VQ. It is unclear what the functional differences are between lamina I-DSTT and lamina V-VSTT
nociceptive specific pathways.
There is some indication of the potential function of the
DSTT. Chung et al. ('86) have shown that in monkeys,
bilateral DLF section results in a decrease in the response
of some thalamic neurons to noxious cutaneous stimulation. Preliminary work in cats has demonstrated a clear
dependence of the responses of some thalamic neurons in
VPL and PO to noxious cutaneous stimuli on ascending
transmission through the DLF ipsilateral to the thalamic
recording site (Hodge et al., '87). These findings are consistent with the previously described behavioral effects of DLF
section in cats, monkeys, and man.
The clear separation of the lamina I ascending input to
the thalamus from the remainder of the spinothalamic tract,
in cats, allows experimental designs to test the relative
importance of these two pathways (DSTT and VSTT), in
acute and chronic preparations, in terms of both physiologic
and behavioral responses to somatic sensory stimuli. The
Functional implications
existence of a DSTT distinct from VSTT in humans would
The cells that are the origin of the VSTT are in laminae have profound clinical implications. This necessitates furIV-V and VII-VIII of the spinal cord. These neurons respond ther studies in primates, which are currently under investo a wide range of cutaneous noxious and innocuous stimuli tigation in our laboratory.
as well as to muscle and visceral stimuli ("revino et al., '72;
Willis et al., '74; Fox et al., '80; Milne et al., '81; Meyers
ACKNOWLEDGMENTS
and Snow, '82a; Foreman et al., '77, '79, '84). The cells
The authors thank Norma Horton for expert technical
contributing to the VSTT project to medial and lateral
assistance, Dr. Paul Sheehe for statistical advice, and Drs.
thalamic nuclei (Carstens and Trevino, '78; Applebaum et
J. Preston and R.P. Dum for reading this manuscript. This
al., '79; Willis et al., '79; Giesler et al., %la, 81b; Meyers
work was supported in part by a gift from the Perkins
and Snow, '82a; Kevetter and Willis, '83, '84; Craig and
Foundation.
Burton, '85; Stevens et al., '85). Medially terminating VSTT
axons originate primarily from cells in laminae VII-VIII
LITERATURE CITED
(Giesler et al., %la). Most of these cells are nociceptivespecific and have large, complex and at times bilateral Albe-Fessard, D., A. Levante, and Y. Lamour (1974) Origin of spinothalamic
receptive fields. Laterally terminating axons in monkeys
and spinoreticular pathways in cats and monkeys. Adv. Neural. 4:157166.
originate from cells in laminae N-V, are of wide dynamic
The VSTT portion of the spinothalamic tract in cats has
been demonstrated here to originate from cells in laminae
IV-V and laminae VII-VIII. There are essentially no lamina
I cell axons traveling in the VQ (Apkarian et al., '85). No
systematic evaluation was made of the differences in the
locations of neurons contributing to the ventromedial and
ventrolateral funiculi.
There is physiologic evidence that can be interpreted as
support for the existence of a dorsolateral spinothalamic
pathway. Electrical stimulation of the isolated DLF, in cats,
results in evoked activity in the ipsilateral ventral basal
complex and the posterior nuclear group of the thalamus
(Calma, '65; Curry and Gordon, '72). The latency of this
evoked activity was reported to be consistent with a direct
spinothalamic projection (Calma, '65), even though a polysynaptic pathway could not be excluded. The latency of the
evoked activity in the posterior group reported by Curry
and Gordon ('72) after stimulation of the isolated DLF
closely approximated that obtained after stimulation of the
ipsilateral VQ and was abolished by a rostral lesion of the
DLF. Behavioral studies (Kennard, '54) in cats have shown
that sectioning of the DLF decreased the response to pinprick stimulation below the level of the spinal cord lesion.
In monkeys it has been demonstrated (Vierck and Luck,
'79) that DLF section done following a VQ section results
in a transient increased tolerance to noxious electrical cutaneous stimuli applied contralaterally.
Preliminary retrograde transport studies in squirrel monkeys indicate the existence of a DSTT in this species (Jones
et al., '85). Indirect evidence supports the existence of a
crossed DSTT in man as well. Spinal lesions confined to the
DLF in humans have resulted in chromatolytic neurons
within the contralateral laminae I, N,and V below the
level of the lesion (Smith, '76). Correlation of clinical findings with the anatomic locations of spinal cord lesions in
humans who underwent percutaneous cervical cordotomy
revealed that discrete lesions of the DLF can result in
contralateral analgesia (Moossyet al., '67; Sweet, '76).
Some investigators have presented physiologic findings
that were considered to be consistent with a ventral projection of lamina I neurons in cats and monkeys (Kumazawa
et al., '75; Price and Mayer, '75). Even though these studies
purported to demonstrate a ventral lamina I projection,
they were not controlled to exclude the possibility of activating axons of lamina I neurons within the DLF, especially since high-amplitude stimulation of the VQ was
necessary to antidromically activate lamina I neurons.
360
Albe-Fessard, D., J. Boivie, G. Grant, and A. Levante (1975) Labelling of
cells in the medulla oblongata and the spinal cord of the monkey after
injections of horseradish peroxidase in the thalamus. Neurosci. Lett.
It75-80.
Apkarian, A.V., R.T. Stevens, and C.J. Hodge (1985) Funicular location of
ascending axons of lamina I cells in the cat spinal cord. Brain Res.
334: 160- 164.
Apkarian, A.V., C.J. Hodge, Jr., M.W. Jones, and R.T. Stevens (1987) Thalaniic terminations of the dorsolateral and the ventrolateral spinothalamic pathways. In L. Pubols (ed): Effects of Injury on Spinal and
Trigeminal Somatosensory Systems. New York: Edinger, p. 513.
Applebaum, A.E., J.E. Beall, R.D. Foreman, and W.D. Willis (1975) Organization and receptive fields of primate spinothalamic tract neurons. J.
Neurophysiol. 38r572-586.
Applebaum, A.E., R.B. Leonard, D.R. Kenshalo, Jr., R.F. Martin, and W.D.
Willis (1979) Nuclei in which functionally identified spinothalamic tract
neurons terminate. J. Comp. Neurol. 1 8 8 5 7 5 5 8 6 ,
Berkley, K.J. (1980) Spatial relationships between the terminations of somatic sensory and motor pathways in the rostra1 brainstem of cats and
monkeys. I. Ascending somatic sensory inputs to lateral diencephalon.
J. Comp. Neurol. 193.283-317.
Berman, A.L., and E.G. Jones (1982) The thalamus and basal telencephalon
of the cat, a cytoarchitectonic atlas with stereotaxic coordinates. Madison, WI: University of Wisconsin Press.
Boivie, J. (1970) The termination of the cervicothalamic tract in the cat. An
experimental study with silver impregnation methods. Brain Res.
I9:333-360.
Boivie, J. (1971) The termination of the spinothalamic tract in the cat. An
experimental study with silver impregnation methods. Exp. Brain Res.
22t331-353.
Boivie, J. (1979) An anatomical reinvestigation of the termination of the
spinothalamic tract in the monkey. J. Comp. Neurol. 186:343-370.
Calma, I. (1965) The activity of the posterior group of thalamic nuclei in the
cat. J. Physiol. 180t350-370.
Carstens, E., and D.L. Trevino (1978) Laminar origins of spinothalamic
projections in the cat as determined by the retrograde transport of
horseradish peroxidase. J. Comp. Neurol. 182t151-166.
Cervero, F., A. Iggo, and V. Molony (1979) Ascending projections of nociceptor-driven lamina I neurones in the cat. Exp. Brain Res. 35135-149.
Christensen, B.N., and E.R. Per1 (1970) Spinal neurons specifically excited
by noxious or thermal stimuli: Marginal zone of the dorsal horn. J.
Neurophysiol. 33293-307.
Chung, J.M., D.R. Kenshalo, Jr., K.D. Gerhart, and W.D. Willis (1979)
Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys. 3. Neurophysiol. 421354-1369.
Chung, J.M., K.H. Lee, D.J. Surmeier, L.S. Sorkin, J. Kim, and W.D. Willis
(1956) Response characteristics of neurons in the ventral posterior lateral nucleus of the monkey thalamus. J. Neurophysiol. 56370-390.
Craig, A.D., Jr., and H. Burton (1981) Spinal and medullary lamina 1
projection to nucleus submedins in medial thalamus: A possible pain
center. J. Neurophysiol. 45443-466.
Craig, A.D., and H. Burton (1985) The distribution and topographical organization in the thalamus of anterogradely-transported horseradish peroxidase after spinal injections in cat and raccoon. Exp. Brain Res.
58:227-254.
Craig, A.D., and K.-D. Kniffki (1984) Response behaviour of feline lumbosacral spinothalamic lamina I neurones to muscular input. In W. Hamann and A. Iggo (eds): Sensory Receptor Mechanisms. Singapore: World
Scientific Publication Co.. pp. 283-292.
Craig, A.D., and K.-D. Kniffki (1985)The multiple representation of nociception in the spinothalamic projection of lamina I cells in the cat. In M.
Rowe and W.D. Willis (eds): Development, Organization and Processing
in Somatosensory Pathways. New York: Alan R. Liss, pp. 347-353.
Curry, M.J., and G. Gordon (1972) The spinal input to the posterior group
in the cat. An electrophysiological investigation. Brain Res. 44;417-437.
Dilly, P.N., P.D. Wall, and K.E. Webster (1968) Cells of origin of the spinothalamic tract in the cat and rat. Exp. Neurol. 21:550-562.
Edinger, L. (1889) Vergleichend-entwicklungsgeschichtliche und anatomiscbe Studien im Bereiche des Centralnervensystems. 2. Uber die Forsetzung der hinteren Ruckenmarkswurzeln zum Gehirn. Anat. Anz.
4:121-128.
Fitzgerald, M., and P.D. Wall (1980) The laminar organization of dorsal
horn cells responding to peripheral C fibre stimulation. Exp. Brain Res.
41t36-44.
Foerster, O., and 0. Gage1 (1932) Die Vorderseitenstrangdurchschneidung
beim Menschen. Eine klinisch-patho-physiologisch-anatomische
Studie.
Z. Gesamte Neurol. Psychiatr. 138:l-92.
M.W. JONES ET AL.
Foreman, R.D., R.F. Schmidt, and W.D. Willis (1977) Convergence of muscle
and cutaneous input onto primate spinothalamic tract neurons. Brain
Res. 224.555-560.
Foreman, R.D., R.F. Schmidt, and W.D. Willis (1979) Effects of mechanical
and chemical stimulation of fine muscle afferents upon primate spinothalamic tract cells. J. Physiol. 286:215-231.
Foreman, R.D., R.W. Blair, and R.N. Weber (1984) Viscerosomatic convergence onto T2-T4 spinoreticular, spinoreticular-spinothalaniic,and spinothalamic tract neurons in the cat. Exp. Neurol. 85:597-619.
Fox, R.E., J.A. Holloway, A. Iggo, and S.S.Mokha (1980) Spinothalamic
neurones in the c a t Some electrophysiologieal observations. Brain Res.
I82t186-190.
Gerfen, C.R., D.D.M. OLeary, and W.M. Cowan (1982) A note on the transneuronal transport of wheat germ agglutinin-conjugated horseradish
peroxidase in the avian and rodent visual systems. Exp. Brain Res.
48r443-448.
Giesler, G.J., Jr., D. Menetrey, G. Guilbaud, and J.-M. Besson (1976)Lumbar
cord neurons a t the origin of the spinothalamic tract in the rat. Brain
Res. 118:320-324.
Giesler, G.J., Jr., D. Menetrey, and A.I. Basbaum (1979) Differential origins
of spinothalamic tract projections to medial and lateral thalamus in the
rat. J. Comp. Neurol. 184r107-126.
Giesler, G.J., Jr., R.P. Yezierski, K.D. Gerhart, and W.D. Willis (1981a)
Spinothalamic tract neurons that project to medial and/or lateral thalamic nuclei: Evidence for a physiologically novel population of spinal
cord neurons. J. Neurophysiol. 46r1285-1308.
Giesler, G.J., Jr., H.R. Spiel, and W.D. Willis (1981b) Organization of spinothalaniic tract axons within the rat spinal cord. J. Comp. Neurol.
195:243-252.
Granum, S.L. (1986) The spinothalamic system of the rat. I. Locations of
cells of origin. J. Comp. Neurol. 247:159-180.
Harrison, P.J., H. Hultborn, E. Jankowska, R. Katz, B. Storai, and D.
Zytnicki (1984) Labelling of interneurones by retrograde transsynaptic
transport of horseradish peroxidase from motoneurones in rats and cats.
Neurosci. Lett. 45r15-19.
Hayes, N.L., and A. Rustioni (1980) Spinothalamic and spinomedullary
neurons in macaques: A single and double retrograde tracer study.
Neuroscience 5r861-874.
Hodge, C.J., Jr., A.V. Apkarian, S.Martini, and R.J. Martin (1987) Lateral
thalamic nociception: The effects of interruption of transmission through
the ventrolateral and the dorsolateral spinothalamic tracts. In L. Pubols
fed): Effects of Injury on Spinal and Trigeminal Somatosensory Systems.
New York: Edinger, pp. 313-320.
Horrax, G. (1929) Experiences with cordotomy. Arch. Surg. 18t1140-1164.
Hultborn, H., and B. Storai (1984) Retrograde transsynaptic labelling of
spinal interneurones following injection of WGA-HRP in peripheral
motor nerves. Acta Physiol. Scand. 120r22A.
Hylden, J.L.K., H. Hayashi, G. J. Bennett, and R. Dnbner (1985) Spinal
lamina I neurons projecting to the parabrachial area of the cat midbrain. Brain Res. 336:195-198.
Itaya, S.K., and G.W. Van Hoesen (1982) WGA-HRP as a transneuronal
marker in the visual pathways of monkeys and rat. Brain Res. 236r199204.
Itoh, K., Y. Yasui, M. Takada, A. Mitani, T. Kaneko, T. Sugimoto, and N.
Mizuno (1984) An anterograde-retrograde transneuronal transport of
conjugates of wheat germ agglutinin with horseradish peroxidase (WGAHRP): Labeling of neurons in the reticular nucleus of the thalamus with
WGA-HRP injected into the posterior column nuclei in the cat. Brain
Res. 323:185-187.
Jasper H.H., and C. Ajmone-Marsan (1954) Stereotaxic atlas of the diencephalon of the cat. Ottawa: National Research Council of Canada.
Jones, M.W., C.J. Hodge, Jr., A.V. Apkarian, and R.T. Stevens (1985) A
dorsolateral spinothalamic pathway in cat. Brain Res. 335188-193.
Kennard, M.A. (1954) The course af ascending fibers in the spinal cord of
the cat essential to the recognition of painful stimuli. J. Comp. Neurol.
100:511-524.
Kenshalo, D.R., Jr., R.B. Leonard, J.M. Chung, and W.D. Willis (1979)
Responses of primate spinothalamic neurons to graded and to repeated
noxious heat stimuli. J. Neurophysiol. 42:1370-1389.
Kevetter, G.A., and W.D. Willis (1983) Collaterals of spinothalamic cells in
the rat. J. Comp. Neurol. 215453-464.
Kevetter, G.A., and W.D. Willis (1984) Collateralization in the spinothalamic tract: New methodology to support or deny phylogenetic theories.
Brain Res. Rev. 7:l-14.
Kim, C.C., and P.L. Strick (1976) Critical factors involved in the demonstration of horseradish peroxidase retrograde transport. Brain Res. 103356361.
SPINOTHALAMIC TRACT
361
Kumazawa, T., and E.R. Perl (1978) Excitation of marginal and substantia Rexed, B. (1954) A cytoarchitectonic atlas of the spinal cord in the cat. J.
Comp. Neurol. 100:297-379.
gelatinosa neurons in the primate spinal cord Indications of their place
i n dorsal horn functional organization. J. Comp. Neurol. 177:417-434.
Rosomoff, H.L., F. Carroll, J. Brown, and P. Sheptak (1965) Percutaneous
radiofrequency cervical cordotomy: Technique. J. Neurosurg. 23,639Kumazawa, T., E.R. Perl, P.R. Burgess, and D. Whitehorn (1975) Ascending
644.
projections from marginal zone (lamina I) neurons of the spinal dorsal
horn. J. Comp. Neurol. 1621-12.
Smith, M.C. (1976) Retrograde cell changes in human spinal cord after
anterolateral cordotomies. Location and identification after different
Kuru, M. (1938) Die Veranderung im Zentralnervensystem bei den 2 Fallen
periods of survival. In J.J. Bonica and D. Albe-Fessard (eds): Advances
von “partieller” Chordotomie. Ein Beitrag zur Frage der Ursprungszelin Pain Research and Therapy. New York: Raven, pp. 91-98.
len des Tractus spinotectalis e t thalamicus. Jpn. J. Cancer Res. 3 2 - 2 5 .
Mantyh, P.W. (1982) The ascending input to the midbrain periaqueductal Stevens,R.T., A.V. Apkarian, M.W. Jones, andC.J. Hodge, Jr. (1985)Medial
and lateral thalamic terminations of the dorsolateral and ventral spigray of the primate. J. Comp. Neurol. 221.50-64.
nothalamic pathways. SOC.
Neurosci. Abstr. 11:577.
McMahon, S.B., and P.D. Wall (1983) A system of rat spinal cord lamina I
cells projecting through the contralateral dorsolateral funiculus. J. Comp. Sweet, W.H. (1976) Recent observations pertinent to improving anterolatera1 cordotomy. Clin. Neurosurg. 23:80-96.
Neurol. 214.217-223.
McMahon, S.B., and P.D. Wall (1985) Electrophysiological mapping of brain- Trevino, D.L. (1976) The origin and projections of a spinal nociceptive and
thermoreceptive pathway. In Y. Zotterman (ed): Sensory Function of the
stem projections of spinal cord lamina I cells in the rat. Brain Res.
Skin in Primates, With Special Reference to Man. Oxford: Pergamon,
333: 19-26.
pp. 367-376.
Menetrey, D., J. De Pommery, and F. Roudier (1984) Properties of deep
spinothalamic tract cells in the rat, with special reference to ventrome- Trevino, D.L., and E. Carstens (1975) Confirmation of the location of spinothalamic neurons in the cat and monkey by the retrograde transport of
dial zone of lumbar dorsal horn. J. Neurophysiol. 52612-624.
horseradish peroxidase. Brain Res. 98:177-182.
Mesulam, M.M. (1978) Tetramethyl benzidine for horseradish peroxidase
neurohistochemistry: A non-carcinogenic blue reaction product with Trevino, D.L., R.A. Maunz, R.N. Bryan, and W.D. Willis (1972) Location of
cells of origin of the spinothalamic tract in the lumbar enlargement of
superior sensitivity for visualizing neural afferents and efferents. J.
cat. Exp. Neurol. 34:64-77.
Histochem. Cytochem. 26t106-117.
Mesulam, M.M., and D.L. Rosene (1979) Sensitivity in horseradish peroxi- Trevino, D.L., J.D. Coulter, and W.D. Willis (1973)Location of cells of origin
of spinothalamic tract in lumbar enlargement of the monkey. J. Neurodase neurohistochemistry: A comparative and quantitative study of
physiol. 36:750-761.
nine methods. J. Histochem. Cytochem. 27363-773.
Meyers, D.E.R., and P.J. Snow (1982a) The responses to somatic stimuli of Vierck, C.J., Jr., and M.M. Luck (1979) Loss and recovery of reactivity to
noxious stimuli in monkeys with primary spinothalamic cordotomies,
deep spinothalamic tract cells in the lumbar spinal cord of the cat. J.
followed by secondary and tertiary lesions of other cord sectors. Brain
Physiol. 329:355-371.
102233-248.
Meyers, D.E.R., and P.J. Snow (1982b) The morphology of physiologically
identified deep spinothalamic tract cells in the lumbar spinal cord of the Voris, H.C. (1957) Variations in the spinothalamic tract in man. 3. Neurosurg. 14.55-60.
cat. J. Physiol. 329:373-388.
Milne, R.J., R.D. Foreman, G.J. Giesler, Jr., and W.D. Willis (1981) Conver- White, J.C., W.H. Sweet, R. Hawkins, and R.G. Nilges (1950) Anterolateral
cordotomy: Results, complications and causes of failure. Brain 73:346gence of cutaneous and pelvic visceral nociceptive inputs onto primate
367.
spinothalamic neurons. Pain 11:163-183.
Molenaar, I., and H.G.J.M. Kuypers (1978) Cells of origin of propriospinal Wiberg, M., and A. Blomqvist (1984) The spinomesencephalic tract in the
cat: Its cells of origin and termination pattern as demonstrated by the
fibers and of fibers ascending to supraspinal levels. A HRP study in cat
and rhesus monkey. Brain Res. 152429-450.
intraaxonal transport method. Brain Res. 291:l-18.
Moossy, J., A. Sagone, and H.L. Rosomoff (1967) Percutaneous radiofre- Willis, W.D., D.L. Trevino, J.D. Coulter, and R.A. Maunz (1974) Responses
of primate spinothalamic tract neurons to natural stimulation of hindquency cervical cordotomy: Pathologic anatomy. J. Neuropathol. Exp.
limb. J. Neurophysiol. 37,358-372.
Neurol. 26:118.
Morin, F., H.G. Schwartz, and J.L. O’Leaiy (1951) Experimental study of Willis, W.D., R.B. Leonard, and D.R. Kenshalo, Jr. (1978a) Spinothalamic
the spinothalamic and related tracts. Acta Psychiatr. Neurol. 26:371tract neurons in the substantia gelatinosa. Science 202986-988.
396.
Willis, W.D., and R.E. Coggeshall(1978b) Sensory Mechanisms of the Spinal
Nijensohn, D.E., and F.W.L. Kerr (1975) The ascending projections of the
Cord. New York: Plenum.
dorsolateral funiculus of the spinal cord in the primate. J. Comp. Neu- Willis, W.D., D.R. Kenshalo, Jr., and R.B. Leonard (1979) The cells of origin
rol. 161t459-470.
of the primate spinothalamic tract, J. Comp. Neurol. 188t543-574.
Peschanski, M., and H.J. Ralston I11 (1985) Light and electron microscopic Zemlan, F.P., C.M. Leonard, L.-M. Kow, and D.W. Pfaff (1978) Ascending
evidence of transneuronal labeling with WGA-HRP to trace somatosentracts of the lateral columns of the rat spinal cord A study using the
sory pathways to the thalamus. J. Comp. Neurol. 236:29-41.
silver impregnation and horseradish peroxidase techniques. Exp. NeuPrice, D.D., and D.J. Mayer (1975) Neurophysiological characterization of
rol. 62298-334.
the anterolateral quadrant neurons subserving pain in M. mulatta. Pain
1:59-72.