Pain 113 (2005) 223–232
www.elsevier.com/locate/pain

Clinical note

Thalamic thermo-algesic transmission: ventral posterior (VP) complex
versus VMpo in the light of a thalamic infarct with central pain
Carmen Montesa,*, Michel Magninb,d, Joseph Maarrawib,d, Maud Frotb,d, Philippe Conversb,d,
François Mauguièrec,d, Luis Garcia-Larreab,d
a

Dept Fisiologı́a, Universidad de Málaga, Campus de Teatinos s/n, 29080 Malaga, Spain
b
EMI 0342, INSERM, Hôpital Neurologique, 59 bd Pinel, 69677 Bron cedex, France
c
EA 1880 UCBL, Hôpital Neurologique, 59 bd Pinel, 69677 Bron cedex, France
d
Federative Institute of Neurosciences (INSERM IFR 19), Lyon, France

Received 9 April 2004; received in revised form 9 September 2004; accepted 16 September 2004

Abstract
The respective roles of the ventral posterior complex (VP) and of the more recently described VMpo (posterior part of the ventral medial
nucleus) as thalamic relays for pain and temperature pathways have recently been the subject of controversy. Data we obtained in one patient
after a limited left thalamic infarct bring some new insights into this debate. This patient presented sudden right-sided hypesthesia for both
lemniscal (touch, vibration, joint position) and spinothalamic (pain and temperature) modalities. He subsequently developed right-sided
central pain with allodynia. Projection of 3D magnetic resonance images onto a human thalamic atlas revealed a lesion involving the anterior
two thirds of the ventral posterior lateral nucleus (VPL) and, to a lesser extent, the ventral posterior medial (VPM) and inferior (VPI) nuclei.
Conversely, the lesion did not extend posterior and ventral enough to concern the putative location of the spinothalamic-afferented nucleus
VMpo. Neurophysiological studies showed a marked reduction (67%) of cortical responses depending on dorsal column-lemniscal
transmission, while spinothalamic-specific, CO2-laser induced cortical responses were only moderately attenuated (33%). Our results show
that the VP is definitely involved in thermo-algesic transmission in man, and that its selective lesion can lead to central pain. However, results
also suggest that much of the spino-thalamo-cortical volley elicited by painful heat stimuli does not transit through VP, supporting the
hypothesis that a non-VP locus lying more posteriorly in the human thalamus is important for thermo-algesic transmission.
q 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Keywords: Spinal projection; Posterior part of the ventral medial nucleus (VMpo); Ventral posterior complex; VPL; Nociception; Evoked potential; Central
pain; Laser-evoked potential

1. Introduction
Neural lesions causing pain primarily involve the
nociceptive and temperature pathways (Boivie, 2003;
Boivie et al., 1989; Bowsher, 1996). It is therefore logical
to consider that thalamic lesions entailing painful symptoms
should concern, at least partially, the thalamic relays of
nociceptive pathways. In humans, thalamic nociceptive
regions were first characterised on the basis of symptoms
* Corresponding author. Address: Dpt of Physiology, School of
Medicine, Universidad de Málaga, C/Campus de Teatinos s/n, 29080
Málaga, Spain. Tel.: C34 952 13 15 77; fax: C34 952 13 16 50.
E-mail address: cmontes@uma.es (C. Montes).

associated with clinical lesions, notably loss of pain and
temperature sensation (Dejerine and Roussy, 1906; Garcin
and Lapresle, 1954; Head and Holmes, 1911; Schuster,
1937), and later by neuroanatomical studies following
spinothalamic tract (STT) transection (Mehler, 1962, 1966).
In animals, characterisation of thalamic nuclei involved in
nociceptive processing has been derived from numerous
anatomical and electrophysiological studies (see Lenz and
Dougherty, 1997; Willis and Westlund, 1997). Both lateral
and medial thalamic regions have been identified in
monkeys and humans as receiving STT terminations, the
most important direct projections ending up in the ventral
posterior complex (VP) (Apkarian and Hodge, 1989;
Boivie, 1979; Jones, 1985; Mehler, 1962, 1966; Ralston

0304-3959/$20.00 q 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.pain.2004.09.044

224

C. Montes et al. / Pain 113 (2005) 223–232

and Ralston, 1992; Willis, 1985; Willis et al., 2001).
Microstimulation and recording experiments too have
supported a role of VP in pain and temperature sensation,
both in monkeys (Apkarian and Shi, 1994; Bushnell et al.,
1993; Casey and Morrow, 1983; Kenshalo et al., 1980) and
in humans (Lee et al., 1999; Lenz et al., 1993a,b; Ohara and
Lenz, 2003). On the basis of such evidences, the VP has
been widely considered as the critical thalamic region for
the sensory-discriminative processing of pain (Jones, 1985,
2002; Willis and Westlund, 1997).
In contrast with this view, Craig et al. (1994) have
suggested a different region, clearly outside the VP limits, as
a specific relay for pain and temperature. After injections of
tracers in layer I of the monkey dorsal horn, these authors
described labelled terminals in a region lying posterior and
inferior to VP, which they named ‘posterior portion of the
ventral medial nucleus’ (VMpo). Anatomical and electrophysiological considerations incited them to definitively
consider the VMpo as the dedicated spinothalamic relay for
pain and temperature sensation in humans (Blomqvist et al.,
1996, 2000; Craig, 2000, 2002, 2003a,b; Craig and
Blomqvist, 2002; Craig et al., 2002), and to propose that
lesions to the VMpo would be the neural substrate for
thalamic pain syndromes (Craig, 2003a). Such diverging
views have originated a vivid controversy as to the
respective contribution of VMpo and VP to the transmission
of nociceptive inputs (Craig and Blomqvist, 2002; Graziano
and Jones, 2004; Jones, 2002; Jones et al., 2001; Price and
Verne, 2002; Ralston, 2003; Treede, 2002; Willis, 1995;
Willis et al., 2001, 2002a,b).
Data obtained in one patient with pain following a
discrete thalamic lesion bring new insights to this debate.
Combined clinical, neuroanatomical and neurophysiological results show that VP is undoubtedly relevant for pain and
temperature transmission in man, and that its lesion can lead
to typical thalamic pain. However, results also demonstrate
that, contrary to the lemniscal system, much of the
nociceptive information conveyed by the STT may not
transit through VP, supporting the presence of an extra-VP
locus involved in thermo-algesic transduction.

2. Patient and methods

During the months that followed stroke, the patient developed
neuropathic pain in the right side of the body. One year after the
stroke, pain had a continuous burning component with ‘stab’
paroxysms, was exacerbated by warm temperatures, and provoked
frequent awakenings from night sleep. Pain was rated 8/10 on a
visual analogue scale (VAS).
Bedside sensory examination included assessment of (a)
thresholds for cotton brush, pinprick and blunt pressure; (b)
joint position sense (blind imitation of contralateral finger and toe
movements, and blind search of the contralateral extremity); (c)
graphaesthesia, (recognition of figures drawn on the hand palm
and the forearm); (d) vibration sense (100 Hz tune fork); (e)
stereognosis (blind recognition of familiar objects put into the
hand), and (f) heat and cold sensory and pain thresholds (30!
30 mm2 thermode Medocw and graded laser stimuli). Examination revealed multi-modal hypaesthesia in the right side of the
body, including elevated thresholds for perception of tactile
stimuli, deficits in joint position sense with some degree of
sensory ataxia, loss of graphesthesia, deficits in stereognosis, and
altered two-point discrimination. Pain and temperature sensations
were also decreased, with right-sided severe hypaesthesia for cold
(threshold lower than 15 8C) and hot stimuli (pain sensation not
obtained with stimuli up to 50 8C on upper and lower limbs).
There were many errors when trying to distinguish pinprick from
blunt touch, and significantly increased pain thresholds for
electrical and thermal (laser and thermode) stimuli (see also
Results). There was mechanical static and dynamic allodynia
over the right lower limb (light brush, and Von Frey hair, calibre
6.65), but no summation hyperpathia. Contact with cold objects
was often felt as unpleasant burning. The patient also described
some loss of smell and taste (partial ageusia), which he
considered being maximal on the right side, but this latter
symptom had partially subsided by the time of the electrophysiological testing. There was no muscle weakness and no muscle
atrophy; motor symptoms consisted in some difficulty for fine
fingers movements and intentional tremor of the right hand.
Background pain, and notably paroxysms, were initially
controlled with carbamazepine, but reappeared rapidly. Gabapentine, lamotrigine, clomipramine, paracetamol-codeine, bromazepam, amitriptyline and oxcarbazepine were subsequently used in
various combinations, without success. Intravenous tests with
morphine, ketamine or placebo were negative. In particular, i.v.
ketamine at 0.20 mg/kg provoked somnolence and increased the
burning background sensations. After multidisciplinary discussion
and failure of pharmacological trials, the patient was scheduled for
inclusion in a motor cortex stimulation (MCS) program.

2.1. Case report

2.2. Neuroimaging investigations

In January 2001, a 51 year-old man developed sudden rightsided paresthesiae with upper limb predominance, weakness of
right lower limb and multiple modal sensory loss, including
marked thermalgesic hypesthesia, due to a left thalamic infarct. He
had a previous history of diabetes, hypertension, hypercholesterolemy and smoking, in addition to a familiar history of stroke. Over
the next months, he developed a severe thalamic syndrome,
the dominant feature of which was pain over the right side of the
body, including the face. After several months of inefficacious
pharmacological therapy (see details below), he was referred to the
multidisciplinary pain unit in Lyon.

MRI showed a well localised left thalamic infarct with no
evidence of other focal brain lesions, notably in the brainstem. In
order to superimpose the T1-weighted magnetic resonance (MR)
images obtained in 3D mode and the corresponding stereotactic
atlas planes of the human thalamus (Morel et al., 1997), MR
coronal images (slice thickness: 1 mm) were cut orthogonal to the
anteroposterior commissure (AC-PC) horizontal plane using
MRIcro software (Rorden and Brett, 2000). The slice passing
through PC was taken as the reference to calculate the
anteroposterior coordinates of the other slices. Scales of MR
images and atlas sections were then adjusted, and MR images

C. Montes et al. / Pain 113 (2005) 223–232

superimposed to their corresponding atlas sections. The best fit
between the two was ensured in the posteroanterior dimension by
superimposing the PC levels and in the mediolateral axis aligning
the medial borders of the thalamus. Thus, anatomical relations
between the ischaemic lesion and the different thalamic nuclei

225

could be established. A similar procedure was done in the
horizontal plane to countercheck the results obtained in the
coronal plane.
As the VMpo nucleus is not featured in the Morel et al. (1997)
atlas, its stereotactic location was obtained from the very detailed

Fig. 1. MRI-to-atlas projections allowing the localization of the thalamic lesion on horizontal (A) and coronal (B) planes. This lesion involves the two anterior
thirds of the VP (including VPL, VPM and VPI) and the entire ventrodorsal extent of this complex. Additional but very limited damage involves the VPMpc
(horizontal plate V 1.8; coronal plate A 3.6) and the most posterior extent of the VLp explaining the partial ageusia and the motor symptoms. No lesions were
found elsewhere in the brain of this patient. VMpo location and limits which are not featured in the Morel et al. (1997) atlas are extrapolated from figures 2 and
4 in Blomqvist et al. (2000). Stereotactic coronal plane A 2.7: unpublished material, by courtesy of A. Morel. White bar in each panel indicates the level of the
vertical or horizontal plane passing through the posterior commissure. L and R: left and right hemispheres, respectively. Scale bar, 5 mm. CeM, central medial
nucleus; CG, central gray; CL, central lateral nucleus; CM, centre median nucleus; Hb, habenula; IC, internal capsule; LD, lateral dorsal nucleus; LGN, lateral
geniculate nucleus; Li, limitans nucleus; LP, lateral posterior nucleus; MD, mediodorsal nucleus (pl, paralaminar; pc, parvocellular; mc, magnocellular
divisions); MTT, mamillothalamic tract; MV, medioventral nucleus; Pf, parafascicular nucleus; PG, pregeniculate nucleus; Po, posterior nucleus; Pu, pulvinar
(A, anterior; L, lateral; M, medial divisions); R, reticular thalamic nucleus; RN, red nucleus; SG, suprageniculate nucleus; SN, substantia nigra; sPf,
subparafascicular nucleus; STh, subthalamic nucleus; VA, ventral anterior nucleus; VLa, ventral lateral anterior nucleus; VLp, ventral lateral posterior nucleus
(d, dorsal; l, paralamellar; v, ventral divisions); VM, ventral medial nucleus (po, posterior division); VPI, ventral posterior inferior nucleus; VPL, ventral
posterior lateral nucleus (p, posterior; a, anterior divisions); VPM, ventral posterior medial nucleus (pc, parvocellular division); ZI, zona incerta.

226

C. Montes et al. / Pain 113 (2005) 223–232

description and illustrations available in Blomqvist et al. (2000).
Based on horizontal sections in their Fig. 4, drawings A and B
exhibiting the PC appeared to be located 300 mm dorsal and ventral
to the stereotactic plane DV 0 of the Morel et al. (1997) atlas,
respectively. In the coronal plane, drawing B of Fig. 2 in Blomqvist
et al. (2000) corresponded to plane AP 0 of the Morel et al. (1997)
atlas. Considering these relationships, VMpo was featured on
Morel et al. (1997) atlas stereotactic planes taking into account the
tridimensional coordinates of its limits measured on Blomqvist et
al. (2000). The final anatomical location of the VMpo with respect
to neighbouring nuclei was identical in Blomqvist et al. (2000)
drawings and corresponding Morel et al. (1997) stereotactic atlas
planes. Thus, the VMpo was posteromedial to the VPL and VPM
nuclei, posteroventral to the centre médian and parafascicular
nuclei and dorsal to the medial geniculate nucleus. It overlapped
more or less with the posterior, the suprageniculate and the limitans
nuclei as classically defined.
2.3. Somatosensory electrical and laser-evoked potentials
Since responses to electrical non-noxious stimuli reflect the
activation of the dorsal column-lemniscal system (Mauguière et
al., 1995), while those to infrared laser stimulation reflect
activation of the spinothalamic system (Plaghki and Mouraux,
2003; Treede et al., 2003), both types of stimuli were used in this
patient to record, respectively somatosensory evoked potentials
(SEPs) and laser-evoked potentials (LEPs).
SEPs were obtained using transcutaneous electrical stimulation
of the median nerve at the wrist. Stimulus intensity was set at motor
threshold for abductor pollicis brevis, plus perception threshold.
This intensity yielded a clearly perceived but non-noxious

sensation distributed over the median sensory territory of the
hand (Mauguière et al., 1995). Recordings were obtained from
Erb’s point (peripheral response), C6 spinous process (segmental
spinal potential), and parietal and frontal scalp sites (brainstem and
cortical potentials). A non-cephalic (shoulder) reference was used
to record cortical and subcortical responses simultaneously
(Mauguière and Desmedt, 1988; Mauguière et al., 1995).
Responses were averaged on line, over a 65 ms analysis time,
which included 5 ms pre-stimulus delay for baseline computation
(Bio-Logicw EP system, Chicago, Illinois).
Laser-evoked potentials (LEPs) were obtained with a CO2laser stimulator (Optilasw France) delivering infrared laser pulses
of 10.6 mm wavelength, beam diameter 3.5 mm and output power
10 W. Laser stimuli were applied to the dorsum of the hand
(superficial branch of the radial nerve territory). The power output
of the stimulator being fixed at 10 W, the amount of thermal energy
delivered (in mJ) depended on the duration of the pulse (in ms).
Thus, for a spot surface of about 10 mm2, 1 ms increase in pulse
duration roughly equalled 1 mJ/mm2 energy density. Pulses were
delivered every 8G3 s. Thresholds for innocuous and painful
sensations were first determined by the method of limits before
recording LEPs. After estimation of psychophysical thresholds, the
stimulus intensity used for LEP recording was set, for both sides, at
80 mJ/mm2, i.e. about 20% above the pain threshold in the normal
side (see Plaghki and Mouraux, 2003; Treede et al., 2003). The
mean subjective intensity perceived after each series of laser
stimuli was rated on a scale going from 0 (no sensation) to 3–4Z
pain threshold, ‘pulling a hair’), to 10 (worst imaginable pain).
Thirty-two scalp electrodes positioned according to the 10–20
international extended system (Jasper, 1958; Klem et al., 1999),
and referenced to the nose, were used for LEP recordings. The

Fig. 2. Somatosensory potentials (SEPs) to activation of the dorsal columns-lemniscal system by 200 ms electric shocks. Responses to stimulation of the normal
side are shown in the upper frame; those to stimulation of the painful (right) side in the lower frame. In each case, the left column shows superimposition of two
consecutive runs, and the right part their average. The cortical responses N20 and P25 were isolated from subcortical components by subtraction of ipsilateral
from contralateral parietal leads (Pc–Pi), and are shown in the lowermost traces on the right (framed). Cortical responses N20-P25 (within frames) were very
significantly delayed and attenuated (K67%) after stimulation of the right (painful) side, while peripheral (N9) and spinal (N13) responses were symmetrical.
Note also slight attenuation of P14, probably due to retrograde degeneration of cuneate-thalamic axons.

C. Montes et al. / Pain 113 (2005) 223–232

continuous EEG (Ceegraphw; Bio-Logic Sys. Corp.) was segmented on line, averaged according to stimulation type, displayed and
analysed using a BPMw System (Orgil Corp., Orgil Medical
Equipment, En Ayalla, Israel). For eye movement artefact control,
the electro-oculogram (EOG) was recorded from an infra-orbital
electrode, also referenced to the nose. Evoked potentials were
averaged off line, after visual inspection and segmentation of the
EEG, baseline correction and artefact removal. After segmentation
(epoching) of the EEG, single trials contaminated by blinks, eye
movements, or any other signal exceeding G50 mV were rejected
previous to averaging, which was performed over 2 blocks of 30
stimulus repetitions each. Brain signals were averaged over
1000 ms using a band pass of 0.3–35 Hz, a gain of 30,000 and a
sampling rate of 256 Hz. A 70 ms pre-stimulus delay was used for
baseline computation.
LEPs were compared against normative data from the laboratory
(Garcia-Larrea et al., 2002; Valeriani et al., 1996) and from
published literature (Devos et al., 2000; Treede et al., 1988). Interside latency asymmetries were considered significant (meanC2.5
SD) if exceeding 30 ms for N2 and 40 ms for P2. Amplitude drop of
the vertex response was significant if it exceeded 30% of the normal
side.
Grand-averaged LEPs from an unpublished series of 8
patients with a lateral medullary infarct (Wallenberg’s
syndrome) were used to illustrate differences in the LEP
pattern of abnormalities as compared to the present case.

3. Results
3.1. Anatomical localization of the lesion
Superposition of MR images and atlas planes (Morel et al.,
1997) is shown in Fig. 1. The lesion was centred on the VP
and involved the ventral posterior lateral (VPL), medial
(VPM) and inferior (VPI) nuclei. It mostly concerned the
anterior two thirds of the VPL. It also encroached, to a lesser
extent, on the VPM and its parvocellular division (VPMpc).
The posterior part of the ventral lateral nucleus (VLp), and
the anterior part of the VPI were also somewhat involved by
the most ventral anterior and posterior extent of the lesion,
respectively. Conversely, the lesion spared the posterior
thalamic nuclear group. In particular, the region that has been
recently isolated as the VMpo nucleus (Beggs et al., 2003;
Blomqvist et al., 1996, 2000; Craig, 2000, 2002, 2003a,b;
Craig and Blomqvist, 2002; Craig et al., 2002) was far
enough from the lesion limits to be considered as not affected
by the infarct.
3.2. Somatosensory evoked potentials (SEPs)
SEP results are shown in Fig. 2. Electrical stimulation of
the median nerve at motor threshold was felt as a tingling,
non painful sensation on either side, but much attenuated
when applied to the right (affected) hand. Stimulation of
the left (normal) side yielded values within normal limits at
peripheral and central levels. In particular, the parietal
cortical complex (N20-P25) peaked at 21.3 and 27.4 ms,

227

Table 1
Latencies of main components of median nerve somatosensory evoked
potentials (SEPs) at peripheral (EP), spinal (N13), brain stem (P14) and
cortical levels (N20, P25)

Amplitude in mV corresponds to the cortical complex N20-P25 peak-topeak. EP, Erb’s point.

respectively, (see Table 1). Stimulation of the right median
nerve yielded peripheral and spinal components with
latencies and amplitudes comparable to those obtained for
the left side. P14 was slightly attenuated, probably due to
retrograde degeneration of cuneate-thalamic projections
(Restuccia et al., 1996). The cortical sensory responses N20
and P25 were significantly delayed (23.3 and 30 ms) and the
N20-P25 amplitude reduced by 67% relatively to stimulation of the normal side (Table 1 and Fig. 2).
3.3. Laser evoked potentials (LEPs)
The subjective pain intensity after each laser stimulus (on
a verbal numerical scale) ranged from 1 to 3/10 on the left
(normal) side, and 0 to 2/10 on the right (affected) side.
Detection and pain thresholds to laser stimuli in the healthy
side were 34 and 65 mJ, respectively, and increased
significantly to 65 and 80 mJ when the affected (right)
side was stimulated. The increase in both thresholds was
significant according to our normative data.
Latency values of the N2/P2 cortical components of
LEPs were, respectively, 260 and 410 ms after stimulation
of the normal side, and were delayed to 340 and
450 ms when the affected (right) side was stimulated
(Fig. 3, Table 2). The 80 ms delay of N2 was significant
(see Methods), while the 40 ms delay of P2 was not.
Amplitude of the N2/P2 complex was reduced from 12
to 8 mV (33%) with respect to the normal side (Fig. 3).
The early lateralised negativity of LEPs, which is the closest
reflect of parietal opercular (SII) activation (Frot and
Mauguière, 1999; Garcia-Larrea et al., 2003), was assessed
using a bipolar montage between the midline frontal
electrode (Fz) and the lateral temporal T3 and T4 electrodes
(Treede et al., 2003; Valeriani et al., 1996). The results were
comparable to those obtained with vertex responses, namely
a significant delay of 65 ms after stimulation of the right
(affected) side, with amplitude decreased by 40%. As shown
in Fig. 3, the ipsilateral temporal negativity after stimulation of the healthy side (left) was greater than the
contralateral negativity following stimulation of the affected
side, which rules out the possibility that amplitude reduction
of early lateralised responses are due to bad electrode
contact.

228

C. Montes et al. / Pain 113 (2005) 223–232

Fig. 3. Cortical responses to spinothalamic activation by CO2-laser pulses (LEPs). Upper part: LEPs recorded over 19 scalp sites, after stimulation of the left
(normal) and right (painful) hands. Two consecutive recording runs of 30 stimuli each are superimposed to assess reproducibility. Measurements were
performed on the average of the two (see text). Note that the ipsilateral temporal negativity after stimulation of the healthy side (left) was greater than the
contralateral negativity following stimulation of the affected side, ruling out the possibility that amplitude reduction of early lateralised responses be due to bad
electrode contact. The lower part of the figure shows superimposition of right vs left hand LEPs (averaged over 2 runs) recorded over the midline (Fz, Cz, Pz)
and lateral (C3, C4) scalp sites, to illustrate latency delay (80 ms) and slight decrease of LEPs (K33%) to stimulation of the painful side. The inset at right
bottom shows the lateralised early LEP negativity (‘N1’) obtained with bipolar montage (T3-Fz and T4-Fz) after stimulation of the healthy (black) and painful
(red) hands. The early negativity was depressed by about 40%, and delayed by 65 ms after stimulation of the affected hand.

4. Discussion

4.1. Neuroradiological localization of the thalamic infarct

The patient reported herein developed central pain
contralateral to a focal thalamic lesion. Evoked potentials
disclosed deficits in both dorsal column-medial lemniscus
(SEPs) and spinothalamic (LEPs) responses. Modifications
were, however, more important for non-noxious inputs than
for the specific activation of noxious spinothalamic
afferents.
Detailed anatomical study demonstrated a restricted
infarct which included most of the VP but respected the
posteromedial region of the thalamus—in particular the
VMpo. The fact that thermo-algesic thresholds and
nociceptive cortical responses were significantly affected
by a lesion sparing this nucleus suggests that the VMpo is
not the only thalamic structure that relays spinothalamic
inputs to the cerebral cortex in man.

Boundaries between thalamic nuclei being particularly
difficult to observe on MRI images, we projected the lesion
onto an outlook of such boundaries issued from a human
thalamic atlas (Morel et al., 1997) (Fig. 1). The accuracy
and appropriateness of this atlas to localize human thalamic
regions has been acknowledged in previous works using a
variety of validation procedures (Behrens et al., 2003;
Table 2
Latencies and amplitudes of cortical laser evoked potentials (LEPs) to
stimulation of the superficial radial territory

C. Montes et al. / Pain 113 (2005) 223–232

229

1973). This branch originating from the posterior cerebral
artery supplies the ventral–lateral–posterior part of the
thalamus, including the VLp, and, directly or through
collaterals, the lateral thalamus and the VP. Conversely, the
region where the VMpo has been located receives its
vascular supply from the paramedian artery (originating
from the basilar communicating artery), which irrigates
a distinct area in the ventromedial thalamus (Macchi, 1997).
Anatomical variations in small thalamic supply vessels are
common, and definite correlations difficult to establish; yet,
the impairment of the VP with preservation of the posterior
nuclei group is consistent with the common thalamogeniculate supply of this thalamic region.
4.2. The VP as a spinothalamic relay in humans

Fig. 4. LEPs in Wallenberg’s syndrome. White arrows on MRI show the
small lateral medullary infarct typically resulting in Wallenberg’s
syndrome. LEPs obtained from midline (frontal, central and parietal) and
lateral temporal electrodes are shown in the upper and lower panels to
stimulation of, respectively, the healthy and affected sides. In Wallenberg’s
syndrome, LEPs are virtually absent to stimulation of the affected side,
contrasting with the results obtained in the lateral thalamic lesion.

Jeanmonod et al., 2001; Magnin et al., 2000, 2001; Niemann
et al., 2000).
Correlations between the lesion localization and clinical
signs also confirmed the accuracy of the thalamic projection
onto this atlas. For instance, the lesion partially included the
VLp (Fig. 1A, plates V0.9-D1.8; Fig. 1B, plate A7.2), a
region heavily connected with both the cerebellum and
motor-premotor cortices (Macchi, 1997; Rouiller et al.,
1994, 1999). In accordance with this, the patient described
motor difficulties for fine movements and a right hand
tremor. Also, the VPMpc appeared to be partially included
within the lesion (Fig. 1A, plate V0.9; Fig. 1B, plate A3.6).
This small nucleus is considered to participate in gustatory
and olfactory sensations (Lenz et al., 1997; Pritchard et al.,
1986), and accordingly the patient described partial ageusia
and anosmia.
According to the MRI-to-atlas projection, the infarct was
localized in the territory of the thalamo-geniculate (inferolateral) artery (Bogousslavsky et al., 1988; Percheron,

Consistent with clinical examination of this patient,
which disclosed hypesthesia to all sensory modes, neurophysiological deficits concerned inputs mediated by both
the dorsal columns-medial lemniscus system (explored by
electrical SEPs) and the spinothalamic tract (assessed by
LEPs). The thalamic regions damaged by the infarct (mainly
the VPL, VPI and VPM) appear therefore to be significantly
involved in the transmission of the thermal and nociceptive
inputs triggered by noxious laser pulses. This agrees with a
bulk of data obtained in human and non-human primates.
Indeed, terminal degeneration in VP was observed after
lesions of the spinothalamic tract in humans and monkeys
(Boivie, 1979; Mehler, 1962, 1966; Mehler et al., 1960).
Also, injection of retrograde tracers in the VP, have
demonstrated many retrogradely labelled neurons in both
laminae I and V of the spinal dorsal horn, where the soma of
most spinothalamic neurons is known to lie (Apkarian and
Hodge, 1989; Willis et al., 1979, 2001). Finally, microstimulation of the VP has been able to provoke pain and
thermal sensations in man (Lenz et al., 1993a; Ohara and
Lenz, 2003). Some of these previous tracing and stimulation
studies have been criticised because of possible spreading of
the retrograde tracer or of electrical stimulus pulses outside
the VP (Craig and Blomqvist, 2002). However, our results
showing attenuated and delayed spinothalamic-mediated
LEPs after a very restricted thalamic lesion of the VP,
sparing other nuclei receiving spinal projections, indicate
that selective damage to this structure can affect the
spinothalamic transmission, and thus confirm the role of
VP as a thermal nociceptive relay in the human thalamus.
4.3. Arguments for a non-VP nociceptive relay
Evoked response changes in our patient were not of the
same magnitude for LEPs and SEPs. Indeed, while
responses to non-noxious stimuli were desynchronised,
poorly reproducible over runs and attenuated by 67%
(Fig. 2), LEPs to noxious laser pulses remained synchronised and were decreased by 33% only (Fig. 3). Although
statistically significant, this moderate abnormality of LEPs

230

C. Montes et al. / Pain 113 (2005) 223–232

contrasts with what can be commonly seen in more caudal
lesions of the spinothalamic tract. In spinal or brainstem
STT lesions, LEPs after stimulation of the affected side are
extremely decreased of abolished (Garcia-Larrea et al.,
2002; Hansen et al., 1996; Kakigi et al., 1991; Treede et al.,
1991, 2003). As shown in Fig. 4, STT lesions at the
medullary level are also associated with highly altered
and desynchronised LEPs which contrast sharply with the
results in this thalamic lesion. The relatively moderate LEP
abnormalities following noxious stimulations suggests that
the VP, although involved in nociceptive transmission, is
definitely not the only relay for spinothalamic inputs in the
human thalamus. As estimated by the amplitude ratio of
LEP between affected and non-affected sides, approximately 60% of the spinothalamic input triggered by the laser
pulses was transmitted to the cortex via thalamic relays
other than the damaged VP. It seems unlikely that up to 60%
of the spinothalamic responses may have been relayed in the
small residual VP volume spared by the lesion. In view of
recent and rather convincing evidence pointing to the
existence of a distinct nucleus (the VMpo) receiving
spinothalamic afferents (Beggs et al., 2003; Blomqvist et
al., 1996, 2000; Craig, 2000, 2002, 2003a,b; Craig and
Blomqvist, 2002; Craig et al., 1994, 2002; Davis et al.,
1999), it appears reasonable to assume that this locus might
indeed represent the thalamic relay of the remaining
spinothalamic fibres that went undamaged through our
patient’s thalamus.
The lesion could potentially have damaged fibre tracts,
such as lemniscal afferents to VP and efferent fibres from
VPL, VPM and VPI. While this agrees with the observed
67% decrease in SEPs amplitude, the very limited decrease
of LEPs departs from what could be expected. Indeed, VPI
concentrates STT afferents (Apkarian and Shi, 1994), and
damage to its efferent fibers as they pass through VPL
toward the cortex should have lead to a much larger
attenuation of LEPs, unless a separate spinothalamic-related
pathway remained spared by the lesion (STT afferents to
more caudal structures such as the posterior group,
including VMpo). The integrity of the efferent fibres issued
from the latter structures can in turn be questioned, but the
exact course of these thalamocortical fibres has not been so
far described. The SEP/LEP dissociation suggests that all or
part of efferent fibres from the posterior group may reach
their cortical targets without crossing the VP, perhaps
through the internal medullary lamina.
4.4. Thalamic lesions and central pain in humans
One prevalent view on the mechanisms of central poststroke pain considers disinhibition of ‘medial’ pain channels
by a lesion affecting the lateral pain pathway ending in VL
(Bennett, 1994; Bowsher, 1996; Tasker, 1990), thus
consistent with the present observation. It has been however
recently proposed that central pain may be the consequence
of lesions interrupting a specific thermosensory pathway

which transmits spinothalamic inputs from dorsal horn
lamina I neurons to the VMpo thalamic nucleus (Bester et
al., 2000; Blomqvist and Craig, 2000; Craig, 2000, 2002,
2003a). According to this view, it may be assumed that
lesions of VMpo, its afferent fibers or cortical targets, are
needed for the development of such types of central pain.
The case we present herein suggests, on the contrary, that
clinically typical central thalamic pain can develop in the
absence of any demonstrable lesion of the VMpo. Our data
rather indicate that, although the VP does not represent the
exclusive sensory thalamic relay for thermal nociceptive
inputs, lesions in this area sparing the VMpo are sufficient to
produce central pain. It is likely, however, that other
patients may present pain after thalamic lesions that do
affect the VMpo, underscoring the proteiform mechanisms
of central pain. Mauguière and Desmedt (1988) analysed
patients with thalamic lesions and central pain, and
distinguished different subtypes associated with different
SEP alterations. In 8 patients thalamic pain coexisted with
intact SEPs (and intact touch and position senses) indicating
complete preservation of the VP. At least three of these
eight patients had clinical loss of pain and/or temperature
sensation, and may therefore have corresponded to ‘pure’
lesions of the posterior nuclei (VMpo?), sparing the VP. Our
patient appears as the mirror image, namely a ‘pure’ lesion
of the VP with a spared VMpo. The fact that both types of
lesions may result in central pain and thermal hypesthesia
supports the concept that the VP, but also more posterior
thalamic nuclei, have an important role in relaying
spinothalamic activity to cortex.

Acknowledgements
This work was supported by a PHRC program (“Mécaécanismes de l’allodynie et traitement par neurostimulation”), n8 2000-16, CHU St Étienne, and by a grant from the
CNP Foundation against pain (“Mécanismes de survenue et
de chronicisation de la douleur neuropathique”, L G-L).

References
Apkarian AV, Hodge CJ. Primate spinothalamic pathways: III. Thalamic
terminations of the dorsolateral and ventral spinothalamic pathways.
J Comp Neurol 1989;288:493–511.
Apkarian AV, Shi T. Squirrel monkey lateral thalamus. I. Somatic
nociresponsive neurons and their relation to spinothalamic terminals.
J Neurosci 1994;14:6779–95.
Beggs J, Jordan S, Ericson A-C, Blomqvist A, Craig AD. Synaptology of
trigemino- and spinothalamic lamina I terminations in the posterior
ventral medial nucleus of the macaque. J Comp Neurol 2003;459:
334–54.
Behrens TEJ, Johansen-Berg H, Woolrich MW, Smith SM, WheelerKingshott CAM, Boulby PA, Barker GJ, Sillery EL, Sheehan K,
Ciccarelli O, Thompson AJ, Brady JM, Matthews PM. Non-invasive
mapping of connections between human thalamus and cortex using
diffusion imaging. Nat Neurosci 2003;6:750–7.

C. Montes et al. / Pain 113 (2005) 223–232
Bennett GJ. Neuropathic pain. In: Wall PD, Melzack R, editors. Textbook
of pain. 3rd ed. Edinburgh: Churchill Livingstone; 1994. p. 201–24.
Bester H, Beggs S, Woolf CJ. Changes in tactile stimuli-induced behavior
and c-Fos expression in the superficial dorsal horn and in parabrachial
nuclei after sciatic nerve crush. J Comp Neurol 2000;428:45–61.
Blomqvist A, Craig AD. Is neuropathic pain caused by the activation of
nociceptive-specific neurons due to anatomic sprouting in the dorsal
horn? J Comp Neurol 2000;428:1–4.
Blomqvist A, Ericson AC, Craig AD, Broman J. Evidence for glutamate as
a neurotransmitter in spinothalamic tract terminals in the posterior
region of owl monkeys. Exp Brain Res 1996;108:33–44.
Blomqvist A, Zhang ET, Craig AD. Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the
posterior portion of the ventral medial nucleus, in the human thalamus.
Brain 2000;123:601–19.
Bogousslavsky J, Regli F, Uske A. Thalamic infarcts: clinical syndromes,
aetiology and prognosis. Neurology 1988;38:837–48.
Boivie J. An anatomical reinvestigation of the termination of the
spinothalamic tract in the monkey. J Comp Neurol 1979;186:343–69.
Boivie J. Central pain and the role of quantitative sensory testing (QST) in
research and diagnosis. Eur J Pain 2003;7:339–43.
Boivie J, Leijon G, Johansson I. Central post-stroke pain. A study of the
mechanisms through analyses of the sensory abnormalities. Pain 1989;
37:173–85.
Bowsher D. Central pain: clinical and physiological characteristics.
J Neurol Neurosurg Psychiatry 1996;61:62–9.
Bushnell MC, Duncan GH, Tremblay N. Thalamic VPM nucleus in the
behaving monkey. I. Multimodal and discriminative properties of
thermosensitive neurons. J Neurophysiol 1993;69:739–52.
Casey KL, Morrow TJ. Ventral posterior thalamic neurons differentially
responsive to noxious stimulation in the awake monkey. Science 1983;
221:675–7.
Craig AD. The functional anatomy of lamina I and its role in post-stroke
central pain. Prog Brain Res 2000;129:137–51.
Craig AD. New and old thoughts on the mechanisms of spinal cord injury
pain. In: Yezierski RP, Burchiel KJ, editors. Spinal cord injury pain:
assessment, mechanisms, management. Seattle, WA: IASP Press; 2002.
p. 237–64.
Craig AD. Pain mechanisms: labelled lines versus convergence in central
processing. Annu Rev Neurosci 2003a;26:1–30.
Craig AD. Specificity and integration in central pain pathways. In:
Dostrowsky JO, Carr DB, Koltzenburg M, editors. Progress in pain
research and management, vol. 24. Seattle, WA: IASP Press;2003b.
p. 197–212
Craig AD, Blomqvist A. Is there a specific lamina I spinothalamocortical
pathway for pain and temperature sensations in primates? J Pain 2002;3:
95–101.
Craig AD, Bushnell MC, Zhang E-T, Blomqvist A. A thalamic nucleus
specific for pain and temperature sensation. Nature 1994;372:770–3.
Craig AD, Zhang ET, Blomqvist A. Association of spinothalamic lamina I
neurons and their ascending axons with calbindin-immunoreactivity in
monkey and human. Pain 2002;97:105–15.
Davis KD, Lozano RM, Manduch M, Tasker RR, Kiss ZH, Dostrovsky JO.
Thalamic relay site for cold perception in humans. J Neurophysiol
1999;81:1970–3.
Dejerine J, Roussy G. le syndrome thalamique. Rev Neurol (Paris) 1906;14:
521–32.
Devos D, Creac’h C, Laureau E, Bourriez JL, Guieu JD. Thulium laser
evoked potentials. Normative values for the arms and legs. Neurophysiol Clin 2000;30:313–22.
Frot M, Mauguière F. Timing and spatial distribution of somatosensory
responses recorded in the upper bank of the sylvian fissure (SII area) in
humans. Cereb Cortex 1999;9:854–63.
Garcia-Larrea L, Convers P, Magnin M, André-Obadia N, Peyron R,
Laurent B, Mauguière F. Laser-evoked potential abnormalities in
central pain patients: the influence of spontaneous and provoked pain.
Brain 2002;125:2766–81.

231

Garcia-Larrea L, Frot M, Valeriani M. Brain generators of laser-evoked
potentials. From dipoles to functional significance. Neurophysiol Clin
2003;33:279–92.
Garcin R, Lapresle J. Sensory syndrome of the thalamic type and with handmouth topography due to localized lesions of the thalamus. Rev Neurol
1954;90:124–9.
Graziano A, Jones EG. Widespread thalamic terminations of fibers arising
in the superficial medullary dorsal horn of monkeys and their relation to
calbindin immunoreactivity. J Neurosci 2004;24:248–56.
Hansen HC, Treede RD, Lorenz J, Kunze K, Bromm B. Recovery from
brain-stem lesions involving the nociceptive pathways: comparison of
clinical findings with laser-evoked potentials. J Clin Neurophysiol
1996;13:330–8.
Head H, Holmes G. Sensory disturbances from cerebral lesions. Brain
1911;34:102–254.
Jasper HH. The ten-twenty electrode system of the International Federation.
Electroencephalogr Clin Neurophysiol 1958;10:371–5.
Jeanmonod D, Magnin M, Morel A, Siegemund M. Surgical control of the
human thalamocortical dysrhythmia. I. Central lateral thalamotomy
against neurogenic pain. Thalamus Relat Syst 2001;1:71–9.
Jones EG. The thalamus. New York: Plenum Press; 1985.
Jones EG. A pain in the thalamus. J Pain 2002;3:102–4.
Jones EG, Lensky KM, Chan VH. Delineation of thalamic nuclei
immunoreactive for calcium-binding proteins in and around
the posterior pole of the ventral posterior complex. Thalamus Relat
Syst 2001;1:213–24.
Kakigi R, Shibasaki H, Kuroda Y, Neshige R, Endo C, Tabuchi K,
Kishikawa T. Pain-related somatosensory evoked potentials in
syringomyelia. Brain 1991;114:1871–89.
Kenshalo DR, Giesler GJ, Leonard RB, Willis WD. Responses of neurons
in primate ventral posterior lateral nucleus to noxious stimuli.
J Neurophysiol 1980;43:1594–614.
Klem GH, Lüders HO, Jasper HH, Elger C. The ten–twenty electrode
system of the International Federation. Electroencephalogr Clin
Neurophysiol 1999;52(Suppl):3–6.
Lee JI, Dougherty PM, Antezana D, Lenz FA. Responses of neurons in the
region of human thalamic principal somatic sensory nucleus to
mechanical and thermal stimuli graded into the painful range. J Comp
Neurol 1999;410:541–55.
Lenz FA, Dougherty P. Pain processing in the human thalamus. In:
Steriade M, Jones EG, McCormick DA, editors. Thalamus, vol. II.
Amsterdam: Elsevier; 1997. p. 617–51.
Lenz FA, Seike M, Lin YC, Baker FH, Richardson RT, Gracely RH.
Thermal and pain sensations evoked by microstimulation in the area of
the human ventrocaudal nucleus (Vc). J Neurophysiol 1993a;70:200–12.
Lenz FA, Seike M, Lin YC, Baker FH, Rowland LH, Gracely RH,
Richardson RT. Neurons in the area of human thalamic nucleus ventralis
caudalis respond to painful heat stimuli. Brain Res 1993b;623:235–40.
Lenz FA, Gracely RH, Zirh DA, Leopold DA, Rowland LH, Dougherty PM.
Human thalamic nucleus mediating taste and multiple other sensations
related to ingestive behavior. J Neurophysiol 1997;77:3406–9.
Macchi G. Thalamic functions as interpreted from human lesions. In:
Steriade M, Jones EG, McCormick DA, editors. Thalamus, vol. II.
Amsterdam: Elsevier; 1997. p. 543–615.
Magnin M, Morel A, Jeanmonod D. Single unit analysis of the pallidum,
thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience 2000;96:549–64.
Magnin M, Jeanmonod D, Morel A, Siegemund M. Surgical control of the
human thalamocortical dysrhythmia. II. Pallidothalamic tractotomy in
Parkinson’s disease. Thalamus Relat Syst 2001;1:81–9.
Mauguière F, Desmedt JE. Thalamic pain syndrome of Dejerine–Roussy.
Differentiation of four subtypes assisted by somatosensory evoked
potentials data. Arch Neurol 1988;45:1312–20.
Mauguière F, Garcia-Larrea L, Murray NMF, Rogers T. Evoked potential
diagnostic strategies. In: Osselton JW, Binnie CD, Cooper R,
Fowler CJ, Mauguière F, Prior P, editors. Clinical neurophysiology.
Oxford: Butterworths-Heinemann; 1995. p. 431–522.

232

C. Montes et al. / Pain 113 (2005) 223–232

Mehler WR. The anatomy of the so-called ‘pain tract’ in man: an analysis of
the course and distribution of the ascending fibers of the fasciculus
anterolateralis. In: French JD, Porter RW, editors. Basis research in
paraplegia. Springfield: Thomas Publishing; 1962. p. 26–55.
Mehler WR. The posterior thalamic region in man. Confin Neurol 1966;27:
18–29.
Mehler WR, Feferman ME, Nauta WJH. Ascending axon degeneration
following anterolateral cordotomy. An experimental study in the
monkey brain. Brain 1960;83:718–51.
Morel A, Magnin M, Jeanmonod D. Multiarchitectonic and stereotactic
atlas of the human thalamus. J Comp Neurol 1997;387:588–630.
Niemann K, Mennicken VR, Jeanmonod D, Morel A. The Morel
stereotactic atlas of the human thalamus: atlas-to-MR registration of
internally consistent canonical model. Neuroimage 2000;12:601–16.
Ohara S, Lenz FA. Medial lateral extent of thermal and pain sensations
evoked by microstimulation in somatic sensory nuclei of human
thalamus. J Neurophysiol 2003;90:2367–77.
Percheron G. The anatomy of the arterial supply of the human thalamus and
its use for the interpretation of the thalamic vascular pathology.
J Neurol 1973;205:1–13.
Plaghki L, Mouraux A. How do we selectively activate skin nociceptors
with a high power infrared laser? Physiology and biophysics of laser
stimulation Neurophysiol Clin 2003;33:269–77.
Price DD, Verne GN. Does the spinothalamic tract to ventroposterior lateral
thalamus and somatosensory cortex have roles in both pain sensation
and pain-related emotions? J Pain 2002;3:105–8.
Pritchard TC, Hamilton RB, Morse JR, Norgren R. Projections of thalamic
gustatory and lingual areas in the monkey, Macaca fascicularis. J Comp
Neurol 1986;244:213–28.
Ralston HJ, Ralston DD. The primate dorsal spinothalamic tract: evidence
for a specific termination in the posterior nuclei (Po/SG) of the
thalamus. Pain 1992;48:107–18.
Ralston HJ. Pain, the brain, and the (calbindin) stain (Comments). J Comp
Neurol 2003;459:329–33.
Restuccia D, Di Lazzaro V, Valeriani M, Mariotti P, Torrioli MG, Tonali P,
Mauguiere F. Brain-stem somatosensory dysfunction in a case of longstanding left hemispherectomy with removal of the left thalamus: a
nasopharyngeal and scalp SEP study. Electroencephalogr Clin
Neurophysiol 1996;100:184–8.

Rorden C, Brett M. Stereotaxic display of brain lesions. Behav Neurol
2000;12:191–200.
Rouiller EM, Liang F, Babalian A, Moret V, Wiesendanger M. Cerebellothalamocortical and pallidothalamocortical projections to the primary
and supplementary motor cortical areas: a multiple tracing study in
macaque monkeys. J Comp Neurol 1994;345:185–213.
Rouiller EM, Tanne J, Moret V, Boussaoud D. Origin of thalamic inputs to
the primary, premotor, and supplementary motor cortical areas and to
area 46 in macaque monkeys: a multiple retrograde tracing study.
J Comp Neurol 1999;409:131–52.
Schuster P. Beiträge zun Pathologie des Thalamus opticus. III. Mitteilung
Archiv für Psychiatrie und Nervenkrakheiten 1937;106:13–53.
Tasker RR. Thalamotomy. Neurosurg Clin N Am 1990;1:841–64.
Treede RD. Spinothalamic and thalamocortical nociceptive pathways.
J Pain 2002;3:109–12.
Treede RD, Kief S, Holzer T, Bromm B. Late somatosensory evoked
cerebral potentials in response to cutaneous heat stimuli. Electroencephalogr Clin Neurophysiol 1988;70:429–41.
Treede RD, Lankers J, Frieling A, Zangemeister WH, Kunze K, Bromm B.
Cerebral potentials evoked by painful laser stimuli in patients with
syringomyelia. Brain 1991;114:1595–607.
Treede RD, Lorenz L, Baumgärtner U. Clinical usefulness of laser-evoked
potentials. Neurophysiol Clin 2003;33:303–14.
Valeriani M, Rambaud L, Mauguière F. Scalp topography and dipolar
source modelling of potentials evoked by CO2 laser stimulation of the
hand. Electroencephalogr Clin Neurophysiol 1996;100:343–53.
Willis WD. The pain system. Basel: Karger; 1985.
Willis WD. Cold, pain and the brain. Nature 1995;373:19–20.
Willis WD, Westlund KN. Neuroanatomy of the pain system and of the
pathways that modulate pain. J Clin Neurophysiol 1997;14:2–31.
Willis WD, Kenshalo DR, Leonard RB. The cells of origin of the primate
spinothalamic tract. J Comp Neurol 1979;188:543–74.
Willis WD, Zhang X, Honda CN, Giesler GJ. Projections form the marginal
zone and deep dorsal horn to the ventrobasal nuclei of the primate
thalamus. Pain 2001;92:267–76.
Willis WD, Zhang X, Honda CN, Giesler GJ. A critical review of the role of
the proposed VMpo nucleus in pain. J Pain 2002a;3:79–94.
Willis WD, Zhang X, Honda CN, Giesler GJ. Reply to commentaries.
J Pain 2002b;3:113–4.