Pain 72 (1997) 13–25

A longitudinal study of somesthetic perceptual disorders in an individual
with a unilateral thalamic lesion
Joel D. Greenspan a , c ,*, Stephen E. Joy b, Sandra L.B. McGillis a,
Christine M. Checkosky c, Stanley J. Bolanowski c
a

Departments of Neurosurgery and Physiology, SUNY Health Science Center, Syracuse, NY 13210, USA
b
Department of Radiology, SUNY Health Science Center, Syracuse, NY 13210, USA
c
Institute for Sensory Research, Syracuse University, Syracuse, NY 13244, USA
Received 22 January 1996; revised version received 10 February 1997; accepted 19 February 1997

Abstract
Several aspects of tactile, thermal and pain perception were evaluated in an individual (R.S.) with a hemorrhagic lesion centered in her
left lateral thalamus. Over a 4-year period, psychophysical evaluations were undertaken every 6–8 months, and five magnetic resonance
(MR) studies were conducted. Early tests (1991–1992) revealed large contralateral deficits in R.S.’s perception of touch, innocuous
temperature, and mechanically evoked cutaneous pain –more so for the upper versus the lower extremity. R.S. showed a similar pattern
for heat pain sensitivity, but a more modest deficit than for mechanically evoked pain. She showed a deficit for cold pain sensitivity on her
foot, but not for her hand. Thresholds for all types of stimuli ipsilateral to the lesion were within a normative range. Late in 1993, R.S.
demonstrated improvements in sensory capacity for touch and mechanically evoked pain contralaterally, although deficits were still
evident. During the same period, heat pain sensitivity improved contralaterally, and strikingly, a permanent, ipsilateral hypersensitivity
to heat pain developed in her hand. Throughout the entire testing period, R.S.’s ratings of perceived unpleasantness matched the patterns of
perceived pain intensity. Thus, the discriminative and the affective dimensions of her pain would change in tandem. However, perceptible
innocuous thermal stimuli evoked no affective response when applied contralaterally, despite being described as pleasant when presented
ipsilaterally. Throughout the testing period, R.S. reported a persistent numbness on her right hemi-body. Only during a 3-month period in
1995 did she experience spontaneous pain, which was referred to her right foot. The only change in psychophysical performance related to
her right foot was a transient but intense thermal allodynia several months prior to her spontaneous pain. The MR studies over this 4-year
period showed changes in the extent of edema, gliosis and/or ischemia that could be related to perceptual changes. Thus, the conspicuous
observations in this thalamic lesion case were: (i) differential effects upon the various pain modalities (mechanical, heat and cold); (ii)
development of thermal allodynia without mechanical allodynia, including an ipsilateral effect; (iii) a deficit in positive affective responses
to temperature; and (iv) the different time courses for changes in evoked somesthetic capacity versus spontaneous paresthesias and
pathological pain.  1997 International Association for the Study of Pain. Published by Elsevier Science B.V.
Keywords: Thalamus; Brain lesion; Psychophysics; Pain; Temperature perception; Touch

1. Introduction
Lesions involving the thalamus frequently produce
alterations of somesthetic capacity, however the type and
extent of perceptual abnormality can vary greatly across
* Corresponding author. Department of Oral and Craniofacial Biological
Sciences, University of Maryland Dental School, Room 5-A-12, 666 W.
Baltimore Street, Baltimore, MD 21201, USA. Tel.: +1 410 7063250;
fax: +1 410 7060865; e-mail: jdg001@dental3.ab.umd.edu

individuals. The ventrobasal complex of the thalamus
(VB: ventral posterior lateral (VPL) and ventral posterior
medial (VPM) nuclei) has received the most attention as the
‘somatosensory thalamus’, with respect to both basic
science and clinical studies. Yet, other regions of the thalamus receive and process somesthetic information, and are
likely to be involved in perception (Albe-Fessard et al.,
1985; Jones, 1985; Willis, 1985; Berkley et al., 1987).
Assuming functional specialization of somatosensory processing in the thalamus, partial thalamic lesions should pro-

0304-3959/97/$17.00  1997 International Association for the Study of Pain. Published by Elsevier Science B.V.
PII S0304-3959 (97 )0 3378-2

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J.D. Greenspan et al. / Pain 72 (1997) 13–25

duce a variety of effects, depending upon the precise regions
involved and the extent of injury. There are only a few
reports providing detailed, quantitative assessments of
somesthetic perceptual capacity following thalamic lesions
(Head and Holmes, 1911; Boivie et al., 1989; Samuelsson et
al., 1994; Vestergaard et al., 1995; Bowsher, 1996). Furthermore, there are no reports describing the temporal changes
in post-lesion somatosensory dysfunction. Such studies are
needed in order to tease apart the neural mechanisms of
various somesthetic perceptions, and to try to understand
the basis for post-injury functional reorganization.
This report presents a detailed, longitudinal evaluation of
an individual (R.S.) who suffered a hemorrhage from a
cavernous hemangioma located within the left thalamus,
and who subsequently received stereotactic radiosurgery.
Various aspects of her somesthetic sensibilities were evaluated repeatedly over a 4-year period. Additionally, the
magnetic resonance (MR) studies that were generated
over this same time period were reviewed for possible functional-anatomical correlations. The results reveal a complex
relationship among the different modalities and qualities of
somatosensory perception. As such, this report stresses the
need to evaluate multiple aspects of somesthetic perception
in any attempt to relate CNS pathology to sensory processing.

2. Methods

right arm and leg, and a greater intensity of numbness over
her right hemi-body. She started taking oral doses of Decadron in early May 1993 through late June 1993. She felt her
symptoms starting to improve in July 1993. Early in 1994,
she felt her motor control was worsening, and she voluntarily remanded her driver’s license. Throughout this entire
period, she maintained her part-time accountant’s assistant
job.
Whenever she was asked to describe the abnormal sensation on her right side, she always referred to it as ‘numb’.
Until February 1995, she never described her paresthesia as
painful, even under direct questioning. When asked to indicate where on the body she felt this numbness, she always
first indicated her right hand/arm and foot/leg. Upon further
questioning, she said that her face and torso also felt numb,
as if a line was drawn down the center of her body. She said
that the numbness could be more intense in her extremities
than her body, but that it was comparable for her upper and
lower extremities. Just how ‘strong a numb sensation’ she
felt could vary from day to day, but at least since 1990, was
always present to some degree. In February 1995, she
reported episodes of painful sensations in the toes of her
right foot. Over the next 3 months, she continued to have
intermittent painful episodes several times a week, and the
pain spread to encompass more of her foot. She described
the pain as tolerable, and it didn’t interfere with her normal
routine, but it was a distinct change from the numbness,
which was otherwise still present. These painful episodes
ceased by the end of May 1995.

2.1. Subject (case history)
2.2. Psychophysical procedures
At the time of the first sensory evaluation (October 1991),
R.S. was a 52-year-old white female, employed as an
accountant’s assistant. At the age of 12, she developed an
abrupt right-sided hemiplegia, from which she gradually
recovered, leaving her with a mild hemiparesis and occasional numbness. This condition was stable for approximately 35 years, at which time she noticed a gradual
deterioration of motor control as well as an increased frequency and intensity of numbness. An MR scan in January
1988 confirmed the earlier diagnosis of a left thalamic arteriovenous malformation, with evidence of a recent hemorrhage.
A clinical examination conducted in March 1991 showed
no evidence of cognitive impairment or dysphasia, and normal visual fields. She scored 98/100 on a modified minimental state exam (Teng and Chui, 1987) administered in
July 1992. Her only other medical complaints were
migraine headaches, which occurred every few months for
most of her adult life. She would take either aspirin or
acetaminophen for these headaches.
In September 1991, R.S. received 2000 cGy in a single
fraction stereotactic radiosurgery procedure. Psychophysical testing began 2 months later. R.S. reported that her
symptoms were relatively stable from this point until early
1993, at which time she felt less capable of controlling her

A wide range of psychophysical tests were administered
over a 4-year period. Typically, R.S. would come to the
Skin Senses Research Laboratory at SUNY Health Sciences
Center for evaluation once a week for 6–8 weeks, every 6–8
months. The vibrotactile tests were conducted at the Institute for Sensory Research at Syracuse University. Any single session lasted 2–3 h, during which time 1–3 different
tests were administered. Within each 6–8-week block, most
tests were administered on two different days. R.S. provided
informed consent to participate in this project, and was paid
$10.00 per hour. This project was reviewed and approved by
the Institutional Review Boards for the Protection of Human
Subjects at SUNY Health Science Center at Syracuse and at
Syracuse University.
2.2.1. Tactile sensitivity
2.2.1.1. Vibrotactile thresholds. Vibrotactile thresholds
were derived using a two-alternative, forced choice
tracking method (Zwislocki et al., 1958). The equipment
and procedures were similar to those described by
Bolanowski et al. (1988). Thresholds were estimated for
stimulation of the thenar eminence at three different
frequencies (1, 10 and 300 Hz), and with two different

J.D. Greenspan et al. / Pain 72 (1997) 13–25

contact areas (2.9 cm2 and 0.008 cm2). This combination of
frequencies and contact areas allowed for selective
evaluation of each of the four mechanoreceptive channels
which have been characterized in the glabrous skin of the
hand (Bolanowski et al., 1988; Greenspan and Bolanowski,
1996).
2.2.1.2. Contact touch thresholds. Detection thresholds for
contact touch were measured using a calibrated series of
monofilaments (Stoelting Aesthesiometer kit). While less
precise than the vibratory threshold test, these stimuli
could be administered on several body sites. We routinely
tested the dorsum of the fingers and the dorsum of the foot
(the same sites used for mechanical pain testing, see
below). A method of limits protocol was used, as
described by Essick (1992) (his Fig. 2).
2.2.1.3. Perception of surface-parallel brushing stimuli.
R.S. performed direction and velocity discrimination
tasks with stimuli provided by a computer controlled
brushing motor stimulator. The equipment and general
protocols are described in Franzén et al. (1984) and
Essick et al. (1991). For these tests, R.S. was blindfolded
and wore headphones that emitted white noise. Every 10 s,
a tone cue was given, followed by a brush stroke stimulus
on the designated test site (either the dorsal surface of the
hand or the dorsum of the foot). During directional
discrimination tests, R.S. first reported if she felt
anything, and if so, what direction she felt any
movement: either toward or away from her fingers (or
toes). During velocity discrimination tests, R.S. first
reported if she felt anything, and if so, at which of three
speeds of movement: slow (1.0 cm/s), medium (5.0 cm/s)
or fast (20 cm/s). Prior to data collection for these sessions,
R.S. sampled the stimuli while visually observing the
brush’s movement.
2.2.2. Mechanically evoked cutaneous pain sensitivity
A modified ascending method of limits protocol was used
to estimate R.S.’s threshold for the perception of sharpness
and pain produced by a small probe applying a specified
force to the skin. The device and protocol are described in
Greenspan and McGillis (1991). Routine testing was performed on the dorsum of digits 2 and 3, and the dorsal surface of the foot just proximal to the toes.
2.2.3. Innocuous temperature and thermal pain sensitivity
2.2.3.1. Thresholds for the perception of coolness and heat
2.2.3.4.
pain. A multiple staircase protocol was used to determine
cool perception threshold and heat pain threshold. A
circular contact thermal stimulator probe (1.2 cm
diameter) was used to produce feedback-controlled
temperature changes. Stimuli were applied on the thenar
eminence, the dorsolateral forearm, the lateral surface of
the calf, or the plantar surface of the foot. The equipment

15

and protocols are described in Taylor et al. (1993) and
Greenspan et al. (1993).
2.2.3.2.
2.2.3.5. Scaling intensity and (un)pleasantness of thermal
and pain sensations. This procedure required R.S. to scale
the intensity (how hot, cold, or painful) and the affective
level (how pleasant or unpleasant) of her thermally evoked
sensations. In one series of tests, a contact thermal
stimulator was used to apply heating stimuli. Stimuli
were applied to either the thenar eminence or the plantar
surface of the foot. For these sessions, the adapting
temperature (AT) was 35°C, and stimuli consisted of
temperature increases (up to temperatures of 39–51°C)
that lasted for 5 s before returning to the AT.
In another set of tests, R.S. would place her hand (or foot)
in a temperature-controlled water bath. At different sessions, water bath temperatures ranged from 0°C to 20°C,
and from 40°C to 47°C. R.S. would keep her hand (or foot)
in the water bath for up to 3 min, or until such time that she
felt it was too painful to continue. At various times while her
hand (foot) was in the water bath, she was presented with the
response protocol.
In both testing situations, the same response protocol was
used. After receiving a temperature change with the contact
stimulator or at the appropriate time during the water bath
tests, R.S. was prompted to report whether she felt warm/
hot, cool/cold, pain (regardless of any accompanying thermal sensation), or nothing. She was then prompted to report
whether her sensation was pleasant, unpleasant, or neutral.
If she reported warm/hot, cool/cold, or pain, she was presented with a visual analog scale (VAS) on a computer
screen. The VAS consisted of a graduated vertical bar
with numbers to the right (0 to 100 by tens), and a set of
verbal descriptors to the left. The placement of verbal
descriptors was based on a procedure described by Rainville
et al. (1992), which was replicated in our laboratory. R.S.
was instructed to verbally give a number that represented
the intensity of her warm (or cool or pain) sensation at that
moment. After giving that response, R.S. was presented
with another numbered VAS, this time with verbal descriptors appropriate for the degree of (un)pleasantness that she
was experiencing.
2.2.3.3. Localization of heat pain sensations. During one
2.2.3.6.
session, R.S. was instructed to localize the heat pain
sensations produced by the contact stimulator. The
contact thermal stimulator (maintained at 49°C) was
moved around from site to site on the right forearm, while R.S. was asked to describe where on her
body she perceived the resulting painful sensation.
During the 5-s stimulus period, R.S. kept her eyes closed.
She reported no tactile sensation associated with placing
the probe on her arm. After the probe was removed, she
was asked to open her eyes, describe the quality of the
sensation she just experienced, and point to where she
had felt it.

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J.D. Greenspan et al. / Pain 72 (1997) 13–25

3. Results
The results from the various psychophysical evaluations
are summarized in Table 1.
3.1. Tactile sensitivity
R.S. was very insensitive to tactile stimuli presented to
her right side. This was clearly demonstrated for vibrotactile
thresholds at the thenar eminence (Fig. 1), and for contact
touch thresholds using monofilament probes applied to the
dorsal surface of her right hand and foot (Fig. 2). Her right
hand initially showed a greater deficit than her right foot.
The vibrotactile thresholds for her left hand were well
within the range of thresholds derived from a group of
healthy female subjects similarly tested (Gescheider et al.,
1994). Between mid-1993 and mid-1994, the tactile sensitivity on her right hand improved, although a deficit was still
apparent. With vibratory stimuli, this improvement was
only observed with the 300-Hz stimuli.
Despite R.S.’s insensitivity to punctate and vibratory
stimuli, she would routinely feel (≥90% detection) a camel’s
hair brush exerting only 5 g of force stroked over her right
hand or foot. However, she could not accurately report
spatial or temporal features of such stimuli. In a two-alternative forced-choice task of directional discrimination,
she performed at chance level on the right hand (53%

correct) and right foot (55% correct), while performing
significantly above chance on the left side of the body
(75% for hand and 71% for foot). She showed similar results
when attempting to discriminate the velocity of the brush
stroke on her hands (right = 48% correct; left = 87.5%
correct).

4. Perception of sharpness and mechanically evoked
pain
As with tactile sensitivity, R.S. demonstrated a large
right-sided deficit with respect to her thresholds for perceiving mechanically evoked, cutaneous pain (Fig. 3), and
sharpness (not pictured). Also akin to her tactile thresholds,
this deficit was initially more pronounced on her hand than
on her foot. Mechanical pain and sharpness thresholds for
her left hand were very close to the median of thresholds
derived from a group of healthy female subjects similarly
tested (Greenspan and McGillis, 1991, 1994). The difference between her right and left hand thresholds were
always more than two standard deviations from normative
values (Greenspan and McGillis, 1994), implying a consistent, significant deficit on her right. When tested in late
1994, a comparable right-sided deficit was observed for the
thenar eminence (Fig. 3, top, inset). R.S. showed an improvement in sensitivity on her right between the mid-

Table 1
Results from psychophysical evaluations
Hand

Foot

Contact threshold

Large R deficit; partial improvement by 1994

Vibration

Large R deficit; partial improvement only
with high frequency by 1994

R deficit, less so than with hand.
No improvement in 1994
Not tested

Contact probe
Water bath

No warm/hot sensation on R
No warm/hot sensation on R (except 6/94)

Contact probe
Water bath

No cool/cold sensation on R
Little cool sensation on R; allodynia on R, 7/94

Mechanical thresholds

Large R deficit; partial improvement late 1993

Contact probe thresholds

Small R deficit; (larger R deficit on forearm);
L hyperalgesia in late 1993

Contact probe scaling

R deficit, except at highest temperature
(no L/R difference 6/92). Over time, R
and L increase sensitivity; development
of L hyperalgesia
R deficit at 45–46°C. No sign of late L
hyperalgesia
No L/R difference, except R hyperalgesia
in 1994; no hyperalgesia in 1995

Touch

Innocuous temperature
Warming

Cooling

Large R deficit
Large R deficit; not pleasant on R;
allodynia on R, 6/94
No cool/cold sensation on R
Cool on R same as L; not pleasant
on R; allodynia on R, 7/94

Pain

Heat

Water bath scaling
Cold

Water bath scaling

R deficit; less so than w/ hand;
partial improvement late 1993
No L/R difference on plantar; small
R deficit on dorsum; (small R deficit
on leg); L hyperalgesia in 1995
No L/R difference

R deficit at 45°C, not at 46°C;
L hyperalgesia 5/95
R deficit, except R hyperalgesia
in 1994; no hyperalgesia in 1995

J.D. Greenspan et al. / Pain 72 (1997) 13–25

17

Fig. 2. Tactile thresholds derived from calibrated monofilaments (Stoelting
Aesthesiometer Kit). Each value is based on a single day’s testing, consisting of two ascending and two descending staircases, except for 1995
data, which is the average of 2 days of testing.

foot, but neither pleasant nor unpleasant for her right (Fig. 4,
bottom).
In July 1994, R.S. found the 20°C water to be intolerably
painful for either her right hand or foot. With repeated
attempts, she removed her right hand or foot within 15 s

Fig. 1. Average thresholds plotted as a function of stimulus frequency for
detection of 1-, 10-, and 300-Hz signals applied to the thenar eminence.
Contactor size was either 2.9 cm2 (top) or 0.008 cm2 (bottom). The arrow
above the open triangle at 1 Hz (bottom graph) denotes that the displacement required for threshold was above the ceiling value of 66 dB (2000
mm). The filled squares represent normative data: the mean of thresholds
derived from an age-matched sample of 10 female subjects (Gescheider et
al., 1994). Error bars signify ±1 standard deviation for the normative
thresholds. Data were collected over a 3-day period in 1993 and a 2-day
period in 1994.

1993 and late 1993 testing sessions; however a deficit was
still evident.

5. Innocuous temperature sensitivity
In general, R.S. was very insensitive to innocuous thermal
stimuli. With the contact thermal stimulator, R.S. never
reported ‘cool’ or ‘cold’ (with temperatures down to
22°C), and rarely reported ‘warm’ or ‘hot’ (with temperatures between 36°C and 44°C) applied to her right hand,
arm, leg, foot, or the right side of her forehead. During
immersion of her right hand in a 20°C water bath, R.S.
reported only slight (July 1992) or no cool sensations
(July 1993; Fig. 4, top). In contrast, she consistently
reported cool sensations for her right foot, at an intensity
level comparable to that for her left foot. Even though R.S.
felt cool sensations of the same intensity in both her feet, she
described the sensation as moderately pleasant for her left

Fig. 3. Thresholds for mechanically evoked cutaneous pain on the digit
dorsum (top) and the dorsal surface of the foot (bottom). Each value is a
mean (plus one standard error) based on four estimates from 2 days of
testing, except that May 1993 data are based on 1 day of testing. The
dotted horizontal line in the upper graph represents the median pain threshold value derived from a group of 24 healthy female subjects tested on the
left hand. The inset at the top right compares thresholds at two sites of the
hand.

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J.D. Greenspan et al. / Pain 72 (1997) 13–25

warmth sensation with her right foot in a 43°C water bath
(Fig. 5, top left and middle). In July 1994 (at the same time
as her cold allodynia described above), R.S. showed a dramatically increased sensitivity to both the 40°C and 43°C
water baths with her right foot (Fig. 5, upper right). She
characterized her sensory experience at this point as a burning pain, but localized only to her big toe. Elsewhere on her
right foot she felt nothing. With her right hand, she still felt
nothing with the warm water, except for a transient (5–10-s)
uncomfortable sensation with the 43°C bath. During subsequent evaluations (October 1994 and May 1995), R.S. reported no pain with bath temperatures of 40–43°C for either
her right hand or foot.
5.1. Heat pain sensitivity

Fig. 4. Scaling of the perceived coolness (top) and (un)pleasantness (bottom) resulting from placing the subject’s hand or foot in a 20°C water bath.

of immersion. She still reported this temperature to be cold
but not at all painful for her left hand or foot. In June 1995,
R.S. reported only a transient cool sensation in her right
hand, and no sensation at all in her right foot in the 20°C
water bath.
When initially tested, R.S. reported either transient or no
warmth sensation when immersing her right hand or foot in
a 40°C water bath in 1992 and 1993. She reported some

R.S.’s heat pain sensitivity was measured in three different ways. Since the various protocols revealed somewhat
different features, they will be considered separately.
5.1.1. Contact stimulator pain thresholds
Despite the very large deficits described with the other
somatosensory submodalities, R.S. showed relatively less
disturbance in heat pain thresholds. In October 1991,
R.S.’s heat pain threshold for her right hand (thenar) was
only 1.1°C higher than for her left hand (Fig. 6, top left). Her
threshold for her right foot (plantar) was 0.5°C lower than
for her left foot (Fig. 6, bottom left). Both of these values
were well within the range of laterality differences derived

Fig. 5. Scaling of the perceived warmth or pain resulting from placing the subject’s hand or foot in water baths of various temperatures. Each data point
represents the perceived intensity after the hand (or foot) was immersed for 1 min.

J.D. Greenspan et al. / Pain 72 (1997) 13–25

19

Fig. 6. Heat pain thresholds over time at four body sites. The dashed horizontal line represents the mean threshold derived from a group of 15 healthy female
subjects, similarly evaluated. Inset graphs in upper and lower left allow for comparisons between two different areas of the hands and the feet. Each threshold
is based on 2 days of testing.

from a group of healthy women tested in the same way
(Taylor et al., 1993). The largest laterality difference was
observed for her forearms (3.9°C), which was the only value
that was more than two standard deviations from the normative data base (Fig. 6, top right).
Over the 4 years of testing, R.S. showed changes in her
heat pain thresholds, which differed somewhat across body
sites. For the right hand, arm and leg, she showed a pattern
of greatest hypalgesia in mid-1993, and markedly improved
(lower) thresholds by the end of 1993. Laterality differences
were always more pronounced for her upper extremity than
for her leg. She demonstrated no laterality difference in heat
pain thresholds on the plantar surface of her feet, until 1995
(Fig. 6, lower left). At that time, the laterality difference was
attributable to a change in the left foot, ipsilateral to the
lesion. She consistently showed a small difference on her
legs (Fig. 6, lower right), and, when tested in 1994, a comparable difference on the dorsum of her foot (Fig. 6, lower
left, inset). Thresholds on her left side were stable, with two
exceptions: her left hand showed a distinctly lower threshold beginning in December 1993 (Fig. 6, upper left), and her
left foot and leg showed the same change in 1995. The left
hand hypersensitivity was demonstrable on both the thenar
eminence and the dorsal surface of digit 3 (the test site for
mechanically evoked pain) (Fig. 6, upper left, inset).
5.1.2. Contact stimulator suprathreshold scaling
A statistically significant laterality difference, equiva-

lent to a 1–1.5°C deficit on the right, was initially observed
for the thenar eminence. Subsequent testing demonstrated no laterality difference in July 1992, and marginally
significant differences after that. In contrast, there was
never a statistically significant laterality difference in pain
ratings for stimulation of her feet (Fig. 7). These results,
then, generally matched those seen for heat pain thresholds
described above. Furthermore, the laterality difference evident in September 1994 is largely due to a left-handed
hypersensitivity, which also paralleled her heat pain threshold results.
When rating both the intensity and unpleasantness of
painful heat stimuli, R.S. would typically rate the unpleasantness as equal to or slightly lower than the pain intensity
(Fig. 8). This trend was consistently observed throughout
the testing sessions.
5.1.3. Water bath suprathreshold heat pain scaling
The earliest evaluation with 45–47°C water baths (July–
October 1992) showed a clearly reduced sensitivity on the
right relative to the left, more so for the hands than the feet
(Fig. 5, top left). Subsequent testing indicated an increased
sensitivity for pain in the right hand and especially the foot
(July 1994), however sensitivity was dramatically decreased
3 months later (Fig. 5, bottom left). In 1995, R.S. demonstrated a hypersensitivity in her left foot to hot water baths
(Fig. 5, bottom right), which was consistent with the lower
heat pain thresholds (Fig. 6, lower left).

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J.D. Greenspan et al. / Pain 72 (1997) 13–25

tions at body sites that were clearly away from the
stimulator. It was not uncommon for her to report that
heat stimulation of her right thenar or forearm produced
painful sensations in her fingers rather than at the site of
stimulation. At other times, even within the same testing
session, she would say that her sensations were well localized to the stimulus site. On some trials, R.S. reported a
painful experience, but she could not localize it at all. R.S.
would also mislocalize or not be able to localize the painful
sensations resulting from mechanical stimuli.
During one test session (December 1993) R.S. was
instructed to report where on her body she felt painful sensations resulting from a 49°C probe being placed at various
sites on her right forearm. Her reports derived from 18 trials
are presented in Table 2. Only a few reports corresponded to
the stimulus site. At other times, sensations were either
displaced, extensively localized (fingers and arm together),
or not localized anywhere. In a similar experiment applying
44–46°C stimuli to her right leg (February 1994), her pain
was localized to within 10 cm of the stimulus site for 18/19
stimuli, and only once did she incorrectly refer to a distal
site more than 20 cm away.
5.4. Temporal extent of evoked pain
During heat pain and mechanical pain testing, R.S. was
occasionally asked to describe how long her sensations perFig. 7. Scaling of pain intensity of heat stimuli applied with the contact
stimulator to the hands and feet, at different time periods. Each data point
represents the mean ( ± standard error) based on eight estimates over 2
days, except the September 1994 data are based on four estimates from a
single day of testing. Note the Y-axis scale change for September 1994.
The P-values in each graph represent the statistical probability of a laterality difference, based on a series of 2-way ANOVAs that considered
stimulus intensity and laterality as factors. P = N.S. indicates that laterality
was not found to be a significant factor at a 95% confidence level.

5.2. Cold pain sensitivity
Cold pain perception was assessed by water bath immersion. Early evaluations used 0°C and 10°C baths, and measured the duration of time that R.S. would keep her hand
immersed. There was no indication of a reduced sensitivity
to cold pain in her right hand, and, if anything, a suggestion
of hypersensitivity with the 10°C water bath (Fig. 9). In
1992 and 1993, R.S. found a 17°C water bath highly painful
for her right hand, but not at all painful for her right foot
(Fig. 10). As mentioned earlier, in 1994 R.S. found the 20°C
water bath intolerably painful for her right hand and foot, so
a 17°C water bath test was not attempted. This cold hypersensitivity was not observed in 1995, and in fact, R.S. was
less sensitive to the 17°C water bath than ever before.
5.3. Pain localization
During many of the sessions evaluating painful sensations, R.S. volunteered that she sometimes felt her sensa-

Fig. 8. Scaling of pain intensity (circles) and unpleasantness (triangles) of
heat stimuli applied to the thenar eminence (top) and plantar surface of the
foot (bottom). Each point represents the mean of eight estimates from 2
days of testing.

J.D. Greenspan et al. / Pain 72 (1997) 13–25

21

which is compatible with post-radiation edema, ischemia
and/or gliosis, extended into the left midbrain, previously
uninvolved areas of the left thalamus, and the left parietal
white matter (Fig. 11, D–F). Based on an MR scan performed in September 1993, there is further progression of
the halo. The most significant changes compatible with
edema/ischemia/gliosis involved the left thalamus and left
parietal white matter (Fig. 11, G–I). Proton densityweighted MR images in February 1994 revealed partial
resolution of the hyperintense halo involving the midbrain,
left thalamus, and left partial white matter (Fig. 11, J–L).
Another scan in July 1995 indicated no significant change
from the 1994 scan.

6. Discussion
Fig. 9. Cold pain tolerance as measured by duration of voluntary hand
immersion in cold water baths. Each bar represents the mean (plus one
standard error) of either two (0°C) or three (10°C) measurements.

sisted. Invariably, she said that the sensations were transient, and lasted approximately the same amount of time on
her right and left sides. Thus, even in those cases when
stimuli were spatially mislocalized, R.S.’s pain perceptions
were temporally normal.

R.S. demonstrated clear deficits in evoked somesthetic
perception with a wide variety of tests. The extent and
time course of the various sensory abnormalities reveal a
complexity of effects that suggest separate mechanisms of
information processing at the level of the thalamus.
6.1. Tactile perception
R.S. had greatly elevated thresholds for detecting in-

5.5. Anatomical evaluation of MRI
An MR scan in March 1991 revealed a nodular lesion
within the left thalamus, demonstrating a hypointense
band of signal peripherally surrounding a nidus of slightly
inhomogeneous increased signal (Fig. 11, A–C). The
hypointense band, noted on both T2-weighted and proton
density-weighted images, is most likely susceptibility-artifact from hemosiderin distribution. The nidus demonstrated
an increased signal on T1-weighted images, which is compatible with blood products (predominantly extracellular
methemoglobin), and indicative of a prior hemorrhage.
Six months after this MR study, R.S. received 2000 cGy
in a single fraction, stereotactic radiosurgery procedure.
A July 1992 MR study revealed a new halo of increased
signal surrounding the left thalamic lesion. This new halo,
Table 2
Projection of pain sensations resulting from 49°C stimulus applied to the
forearm (18 trials)
Perceived site of pain

Number of trials

Correctly localized within
10 cm of stimulus
Discretely localized more than
10 cm away from stimulus
Diffusely localized on arm
Diffusely localized on fingers
and arm
Could not localize at all
Felt no sensation

3
2
1
4
6
2

Fig. 10. Pain intensity ratings during submersion of hand or foot in a 17°C
water bath.

22

J.D. Greenspan et al. / Pain 72 (1997) 13–25

tive than single site stimulation in transmitting signals
through the compromised thalamus. Even though R.S.
could routinely detect a brushing stimulus on her hand or
foot, she could not extract directional or velocity information from such a stimulus.
6.2. Mechanical pain versus heat pain perception

Fig. 11. Axial proton density weighted MR images. The size and configuration of the left thalamic hemorrhage is stable over time. Note changes
in surrounding edema/ischemia/gliosis. A–C: March 1991. Hemorrhagic
lesion in left thalamus, with little surrounding edema/ischemia/gliosis.
D–F: July 1992. Progression of edema/ischemia/gliosis inferiorly to left
midbrain, previously uninvolved areas of the left thalamus, and left parietal white matter. G–I: September 1993. Stable findings in midbrain;
additional increase of edema/ischemia/gliosis in left thalamus, and left
parietal white matter. J–L: February 1994. Partial resolution of edema/
ischemia/gliosis in midbrain, left thalamus, and left parietal white matter.

nocuous mechanical stimuli. The significant laterality differences in threshold curves across all vibratory frequencies indicates a diminution in tactile perception across all
mechanoreceptive channels (Bolanowski et al., 1988). R.S.
showed a selective improvement in threshold with high
frequency vibration in 1994 (Fig. 1), suggesting an improvement in sensory transmission only from PC mechanoreceptors. This observation lends support to the idea that
information from PC mechanoreceptors is processed separately from other cutaneous mechanoreceptor input at the
thalamic level (Dykes et al., 1981; Kaas et al., 1984; Herron
and Dykes, 1986). R.S. also showed lowered contact touch
thresholds during this same period (Fig. 2), but only for her
hand. Since monofilament stimulation excites all types of
cutaneous mechanoreceptors, including PCs (Johansson et
al., 1980; LaMotte and Whitehouse, 1986), one would
expect better performance on contact touch detection with
improvement in any of the mechanoreceptive channels.
Despite the high tactile thresholds on the right side, R.S.
could routinely detect light brushing along her skin. This
may be due to the fact that surface parallel brushing is a
particularly good stimulus for activating cutaneous mechanoreceptors (Greenspan, 1992; Edin et al., 1995; Essick and
Edin, 1995). Or, it may be that the spatio-temporal pattern
of successively activated mechanoreceptors is more effec-

In some respects, mechanical and heat pain thresholds
showed similar patterns. For both, deficits were greater for
the upper body than the lower body, at least initially. Also,
thresholds on the right side were highest in mid-1993, and
clearly improved by late 1993 or early 1994. These trends
were also observed for tactile thresholds (see above), and
thus, could be considered global features of R.S.’s somesthetic disturbance.
However, in other respects, there were distinct differences between mechanically evoked and heat evoked
pain. First, the degree of deficit in pain threshold, expressed
as the number of standard deviations (SDs) beyond the normative laterality differences, was consistently larger for
mechanically evoked pain (always greater than 2 SDs)
than for heat pain (usually less than 2 SDs). This difference
was apparent for both the hand and the foot. Secondly, there
was a dramatic thermal allodynia observed in June–July
1993, but never evidence of a mechanical allodynia.
Thirdly, there was a dramatic decrease in heat pain threshold for the left hand after mid-1993 (Fig. 6), and a corresponding increase in pain intensity scaling for contact heat
stimuli applied to that hand (Fig. 7, September 1994). This
ipsilateral change in heat pain sensitivity was observed on
both palmar and dorsal surfaces (Fig. 6, upper left), but was
not seen for mechanical pain sensitivity tested on the same
skin sites (Fig. 3, top, inset).
Very few reports have evaluated both mechanical and
thermal pain perception for people with central lesions.
Boivie et al. (1989) performed extensive sensory testing
upon nine people with lesions involving the thalamus. All
nine demonstrated elevated thermal pain thresholds on body
sites contralateral to their lesion, but 8/9 were hyperalgesic
to pin prick, and only one was hypoalgesic. While this is not
the same pattern as described in the present report, it
demonstrates the ability of thalamic lesions to dissociate
effects upon thermal pain versus mechanical pain perception. A recent study describing the sensory capacities of
central post-stroke pain (CPSP) patients reported that 80%
were hypoalgesic to pin prick, but only one-quarter had
‘clearly elevated’ heat pain thresholds (Vestergaard et al.,
1995).
Although many nociresponsive thalamic neurons are
reported to be excited by both noxious heat and noxious
mechanical stimuli, a sizable fraction only respond to noxious mechanical stimuli. One systematic study of such neurons in the VPLc of monkey thalamus described approximately 20% (13/67) of the mechanically nociresponsive
neurons to be unresponsive to noxious heat stimuli up to

J.D. Greenspan et al. / Pain 72 (1997) 13–25

50°C (Kenshalo et al., 1980). A subsequent study from the
same laboratory revealed that of a sample of 39 neurons
responsive to noxious mechanical stimuli, only nine also
responded to temperatures up to 49°C (Chung et al.,
1986). More recently, an investigation of single-unit recordings in the human ventral caudal thalamus (analogous to the
monkey VPLc) reported that 64% (7/11) of the mechanically nociresponsive neurons were unresponsive to heat stimuli up to 51°C (Lenz et al., 1994). Thus, a significant
fraction of nociresponsive neurons in the main somatosensory nucleus of the thalamus are only responsive to mechanical stimuli, and their injury would presumably have a selective effect upon mechanically evoked versus thermally
evoked pain. This relationship suggests that the core region
of ventral caudal thalamus has particular importance for
both mechanically evoked touch and pain perception, and
less critical importance for thermally evoked sensations. An
alternative interpretation is that the mechanically nociresponsive neurons may be more susceptible to injury, at
least in this case.
6.3. Heat pain versus cold pain
Sensitivity to painfully cold stimuli did not parallel heat
pain sensitivity. Initially, R.S. was equally sensitive to painfully cold stimuli applied to either hand, and less sensitive to
painfully cold stimuli applied to her right versus left foot,
the opposite somatic pattern of heat pain sensitivity. In
1994, R.S. demonstrated a prominent cold hypersensitivity
for her right hand and foot. At the same time, she demonstrated a heat hypersensitivity for her right foot in 40–43°C
water baths, but not for her right hand.
Other evaluations of CPSP patients have shown that heat
pain and cold pain perception can be differentially affected
by a lesion of the spino-thalamo-cortical system (Vestergaard et al., 1995). Thus, one must consider that thalamic
processing relevant to heat pain and cold pain perception is
separable at the level of the thalamus.

23

An unexpected alteration in affective processing was
found with respect to innocuous thermal stimuli. Even
though R.S. perceived a 20°C water bath to be moderately
cool with either her left or right foot, she only considered it
pleasant with her left foot, and described it as neither pleasant nor unpleasant with her right foot (Fig. 4). These results
suggest the intriguing possibility of a selective perturbation
of positive affective processing of somesthetic input resulting from this lesion.
6.5. Paresthesia, central pain, and sensory deficits
Even though deficits in pain and/or thermal perception
frequently accompany CPSP (Boivie et al., 1989; Tasker
et al., 1991), central lesions can produce such sensory deficits without the appearance of pathological pain (Agnew et
al., 1983; Andersen et al., 1995; Bogousslavsky et al., 1988;
Samuelsson et al., 1994). Thus, while disruption of the thermal and/or pain sensory systems may be necessary for
pathological pain to develop, it is not sufficient. There
was no striking correlation between the spontaneous paresthesias or pains that R.S. experienced, and the sensory
deficits measured psychophysically. Throughout the testing
sessions, R.S. described a hemi-body numbness on her right
side. Beginning in February 1995, R.S. reported intermittent
pain sensations in the toes of her right foot. Over the next
few months, these pains spread to encompass a good portion
of her foot, before disappearing in May 1995. There was no
dramatic change in somatosensory test performance associated with the development of R.S.’s pain during this period. The only related phenomenon was R.S.’s intense heat
allodynia in her right foot 8 months earlier. She also experienced a cold allodynia at that time, but it was present in both
her hand and foot, and she never reported any spontaneous
pain in her hand. The relationship between thermal allodynia and central pain development is suggestive in this case,
but clearly requires further evaluation.
6.6. Thalamic neuropathology and lesion effects

6.4. Affective responses to stimuli
When experiencing painful thermal stimuli, R.S. would
routinely rate the unpleasantness to be slightly less than the
intensity of the pain. Such a response pattern has been commonly described for neurologically intact subjects performing these tasks (Price et al., 1983, 1987; Rainville et al.,
1992). In this respect, R.S. showed affective evaluations
appropriate for her reported intensity of pain. She also
showed appropriate emotive reactions to the intensely painful stimuli during the test session, such as verbal exclamations and facial grimaces. Thus, both of the measured pain
dimensions, perceived intensity and unpleasantness, were
altered in tandem whenever perception was abnormal.
This result suggests that lateral thalamic regions process
nociceptive information relevant to both sensory-discriminative and affective dimensions of pain.

R.S. sustained at least one hemorrhagic incident prior to
the start of the sensory testing. There was no indication of
additional bleeding in subsequent MR studies throughout
this period. Instead, subsequent changes are consistent
with post-radiation effects: white matter damage with nonspecific changes to myelination, vacuolation, edema, and
gliosis. These pathologies result at least in part from small
vessel damage, especially within the deep portions of the
brain (Kirkwood, 1990). Apparent collateral areas of damage occurred within the left midbrain, previously uninvolved regions of the left thalamus, with extension into
the white matter of the left parietal lobe. This collateral
damage could represent edema, gliosis and/or ischemic
changes, which cannot be differentiated on the basis of
the MR studies available.
With reference to an atlas of human thalamic anatomy

24

J.D. Greenspan et al. / Pain 72 (1997) 13–25

(Dewulf, 1971), the hemangioma and surrounding hemosiderin occupy a major portion of the left VB complex,
encompassing most if not all of the VPL and ventral posterior inferior (VPI) nuclei, major receiving nuclei of nociceptive input from the spinal cord (Bowsher, 1957; Berkley,
1980; Jones, 1985; Gingold et al., 1991). The hemangioma
encroaches somewhat medially, but clearly spares portions
of the medial thalamus. It has long been suggested that the
VB area of the thalamus is important, if not essential, for the
‘sensory-discriminative’ aspects of touch and pain, that is,
the ability to discriminate the intensive, spatial and temporal
aspects of a stimulus (Melzack and Casey, 1968; Albe-Fessard et al., 1985; Willis, 1985). In the present case, the
various discriminative dimensions of heat pain were
affected to different extents. Specifically, spatial localization was grossly distorted, intensity scaling was offset near
the threshold range, but otherwise appropriate, while the
temporal perception of heat pain was unaffected. An investigation of the somesthetic response properties of medial
thalamic neurons in the awake monkey may be relevant
here. Bushnell and Duncan (1989) demonstrated that some
of the medial thalamic neurons could encode noxious heat
intensity to the same extent as lateral thalamic neurons,
however these medial thalamic neurons have very large
(non-discriminating) receptive fields on the body. These
observations suggest that portions of the medial thalamus
receiving nociceptive input have the ability to preserve stimulus intensity information, but not necessarily spatial
(somatotopic) information. If so, one would expect that a
laterally located lesion would have the differential effects
upon intensive and spatial aspects of pain perception that
were observed in the present study.
The particular pattern of heat pain hypalgesia, only at the
lower end of the range (Figs. 5, and 7), was similar to the
pattern produced by an individual with a corpus callosum
lesion (Stein et al., 1989). This ‘split-brain’ case was tested
in a manner so that the subject would report perceptions
resulting only from information relayed via ipsilateral
spinal cord and brain stem pathways. Thus, the heat pain
scaling pattern revealed by R.S. could be based on sensory
input solely mediated by ipsilateral pathways.
Due to the ambiguous boundaries of edema, gliosis and
ischemia, it is not possible to precisely demarcate the extent
of pathological versus normal tissue of the thalamus and
surrounding areas in this case. The more posterior regions
of the thalamus that are known to receive spinothalamic
input (Bowsher, 1957; Berkley, 1980; Jones, 1985; Gingold
et al., 1991; Craig et al., 1994) were within the hyperintense
halo surrounding the hemangioma. At least some of the
sensory changes paralleled MR-observable changes in the
hyperintense halo, and thus may be related to changes in
neural tissue function within the halo region. Specifically,
the maximum extent of the halo (and presumably its greatest
influence on thalamic processing) was observed in the September 1993 MR study, while the highest thresholds contralaterally for all tests were recorded in the spring (touch

and mechanical pain) or summer (heat pain) of 1993. The
next MR study (February 1994) showed a significant resolution of this halo, and R.S. demonstrated improved (lower)
thresholds in the same tests during late 1993 and early 1994.
It is perhaps significant that the thermal allodynias and
spontaneous pain only developed after the resolution of
the cerebral edema, and after partial sensory recovery.

Acknowledgements
This research was supported by NIH grants NS-28559
and DC-00098. We gratefully thank R.S. for her long-standing cooperation and goodwill throughout this study. We also
thank Jeffrey A. Winfield, MD, PhD, for his assistance in
this project.

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