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Stereotact Funct Neurosurg 2002;78:192–196
DOI: 10.1159/000068965
Transcranial Magnetic Cortical
Stimulation Relieves Central Pain
S. Canavero V. Bonicalzi M. Dotta S. Vighetti G. Asteggiano
D. Cocito
Pain Relief Unit, Department of Neurosciences, Molinette Hospital, Turin, and
Service of Clinical Neurophysiology, City Hospital, Alba, Italy
Key Words
Central pain W Transcranial magnetic stimulation W Motor cortex
stimulation W Propofol
Extradural cortical stimulation for neurogenic pain is a recent addition
to the field of functional neurosurgery. About 50% of patients with central
pain draw benefit in the long run. However, there is an urgent need for prognostic factors in order to cut the costs of the procedure. In this paper we
report a statistically significant correlation between the subhypnotic propofol test, transcranial magnetic cortical stimulation (TMS) and the actual
short-term outcome of extradural cortical stimulation in 9 patients. The propofol test and TMS appear to predict short-term effects of extradural cortical
Copyright © 2002 S. Karger AG, Basel
Extradural motor cortex stimulation (MCS) is known to allay central pain
(CP) [1]. Yet, not all series found a benefit and in several cases this was soon lost
[1]. In 1995, Migita et al. [2] reduced CP in 1 patient but not in another with
single-pulse transcranial magnetic cortical stimulation (TMS). TMS is a tech-
© 2002 S. Karger AG, Basel
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E-Mail [email protected]
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nique currently employed for both diagnostic and therapeutic purposes [3]. In
1998, we reported that TMS can allay both CP (5 patients) and neuropathic pain
(4 patients) [4]. These results have been confirmed [5–7].
We submitted 9 new patients suffering CP to TMS in order to correlate this
with the propofol test, a procedure known to predict short-term benefit of MCS
[1]. The propofol test is cheaper than TMS and widely available.
Patients and Methods
Between March 2001 and May 2002, 9 patients suffering CP were treated with TMS.
There were 3 women and 6 men (age range: 40–66). Their CP was due to brain ischemia (1),
brainstem ischemia (1), both (1), thalamic hemorrhage (2), spinal cord ischemia (1), spinal
cord injury (2), or syringomyelia (1). Their syndromes fulfilled IASP criteria for CP. Maximal
pain was generally referred to the upper or lower limbs. After obtaining written informed
consent, these patients were assessed for quality and intensity of their pain and presence of
allodynia. Intensities were rated on a Visual Analog Scale and Numerical Rating Scale.
Each patient was submitted to TMS with a Magstim Bistim module (Spring Gardens
Wales, UK) which delivers 90% of maximal power of the Model 200 unit which we performed our previous study [7]. Two trains of 10 stimuli at maximal power (100% of machine
capability) with a maximal frequency of 0.2 Hz and an intertrain interval of 10 s (time for
intermodule switch) were delivered to the motor cortex contralateral to the pain. The arm or
leg areas were identified anterior to the scalp projection of the rolandic fissure [1], and motor
responses were sought by visual inspection of the patient’s movements. Stimulation was
applied where the strongest responses were obtained. A figure-of-eight and a double-cone
coils were used, respectively, for arm and leg stimulation.
Pain was assessed by a VAS/NRS scale starting at the end of the first train, then every
10 min for an hour; the presence of allodynia was specifically explored. Patients were
instructed to self-assess their pain and presence of allodynia for the following 24 h. In
responsive cases, a placebo effect was excluded by sham stimulation of the contralateral side
(same parameters as above). It was explained that, even though motor responses could be
elicited on the unaffected limbs, pain elaboration in the brain took place in both hemispheres and thus that both sides had to be explored.
Prior to TMS, all patients submitted to a propofol test (0.2 mg/kg i.v. bolus) and placebo match (see full description in ref. [8]). Propofol is completely cleared from the bloodstream in about 5 min, and in these patients all benefits for pain disappeared within 30 min
during which pain was assessed.
Efficacy of both TMS and propofol was broken down into 4 categories: no relief (0–
25% reduction), fair (26–50% reduction), good (51–75% reduction), and excellent (76–
100% reduction). A test had to produce at least 26% pain reduction to be considered positive. An a priori 15% difference between results from the two tests is considered acceptable
in this preliminary study, as it would not interfere with patients’ management. The strength
of correlation between pain relief obtained with the propofol test and TMS was accessed
with the non-parametric Spearman rank correlation coefficient. The agreement between the
two methods was assessed with the Bland-Altman method [9]. In all cases, p ! 0.05 was
considered significant.
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Transcranial Magnetic Cortical Stimulation
Relieves Central Pain
Fig. 1. Correlation of pain relief.
Sham stimulation was always ineffective. Two patients were temporarily
worsened by TMS stimulation, 3 patients obtained no benefit (0–25%), 1 had his
allodynia but not his spontaneous pain totally abolished for about 30 min, while 3
had both spontaneous pain and allodynia relieved (2 fair, 1 good). In these last 3
patients, relief lasted, respectively, for less than 1 h, 4 h and 16 h. There was no
difference in the non-responders in terms of pain localization compared to
responders (i.e. upper and lower limbs were equally distributed in the two
groups). Patients who had their pain worsened returned to baseline within
30 min. No epileptic seizures were elicited. The procedure was well tolerated by
all patients. The propofol test, but not placebo, reduced the pain and/or allodynia
in the same patients as TMS (it abolished allodynia but not spontaneous pain: 1
patient; fair 2; good 1), while it had no effect in the others.
The strength of correlation between propofol test and TMS was significant
(Spearman rank correlation coefficient, r = 0.892, p = 0.002; fig. 1). The BlandAltman analysis demonstrates a good agreement between the two tests (fig. 2).
One patient who obtained no benefit and one who obtained fair relief went
on to implantation of an extradural motor cortex stimulator (RESUME, Med-
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Fig. 2. Bland-Altman curve.
tronic Inc., Minneapolis, Minn., USA) (see description of procedure in ref. [1]).
The same results were observed at short-term follow-up (no effect and fair
TMS may partially and temporarily relieve CP up to 16 h. Unlike previous
studies [2, 6–7], we specifically assessed any possible effects on allodynia and
observed that TMS may reduce allodynia but not spontaneous pain. Pain was
reduced with our protocol despite a much lower frequency, as observed by the
French group [6, 7] with rTMS. Likely, the different power outputs of the Bistim
Set-up (and also the Model 200) are to be allowed for.
How TMS works to allay pain is a matter of speculation. It is possible, in
view of the correlation with propofol, a GABA A agonist, that TMS brings about a
GABA-mediated renormalization of cortical activity. Our preliminary data in 2
patients plus another from our previous series [4] suggest that there exists a correlation between relief by TMS and MCS, although the magnitude of relief may not
be the same. Importantly, in our series, responsiveness to the propofol test [8]
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Transcranial Magnetic Cortical Stimulation
Relieves Central Pain
predicted response to TMS. If confirmed, this might spare the patient the TMS
trial before surgical MCS. In fact, we found that TMS analgesia may be 17.5%
below or 4.1% greater than the propofol test, which would be acceptable for such
clinical purposes.
In conclusion, this preliminary study shows that both propofol and TMS may
temporarily reduce central pain in some patients and might also predict which
patients will obtain benefit from MCS.
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