European Journal of Pain 7 (2003) 365–367

www.EuropeanJournalPain.com

Ulf Lindblom and spinal cord stimulation

Bj€oorn A. Meyerson *

Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institute/Hospital, Stockholm, Sweden

Received 28 March 2003; accepted 8 April 2003

In the early years of spinal cord stimulation (SCS), or

dorsal column stimulation (DCS) as it was then called,no attention was paid to the possibility that this new

treatment modality could be preferentially effective for

different types of pain. At that time not even the crude

differentiation between nociceptive and neuropathic

pain was yet universally recognised. In fact, pain was

then dealt with as an entity regardless of aetiology and

pathophysiology and it was managed and looked upon

as just ‘‘pain’’. The only exception was causalgia, orRSD, in which sympathetic dysfunction was consid-

ered to be the key pathophysiological factor. SCS was

developed as a direct practical application of the gate-

control theory, which had offered a model for modula-

tion of acute nociceptive pain. With this conceptual

framework it is not surprising that SCS at that time was

applied to virtually all forms of chronic pain, which had

proven to be unresponsive to analgesics – or blockswhich were in those days extensively practised. Thus,

there was good reason to expect that SCS should have a

universal antinoniceptic effect, but there were some few

exceptions. For example Nashold and Friedman (1972)

stated that the most satisfactory pain relief could be

obtained in cases of burning pain of central origin.

However, as a rule SCS was applied on very wide indi-

cations and the long-term outcome, when the initialplacebo effect had subsided, was poor.

Already Shealy who was the inventor of SCS had

looked for possible effects on induced pain and reported

that the perception of pinprick was attenuated (see

Shealy et al., 1967). This finding could not be confirmed

by Nashold et al. (1972) who also made the crucial ob-

servation that SCS did not influence the acute pain of an

intercurrent bone fracture in spite of good relief of achronic pain in the same extremity. In that situation,

there was good reason to explore in more detail how

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doi:10.1016/S1090-3801(03)00048-X

SCS might influence cutaneous sensitivity to noxious

and innocuous mechanical and thermal stimuli and apossible relationship to the relief of spontaneous, on-

going pain. Ulf Lindblom, who had since long been

much interested in sensory psychophysics was attracted

by the possibility of studying such patients, and in the

early 1970s we established a close collaboration. It could

be mentioned in this context that we then also created

together with Staffan Arn�eer, the anaesthesiologist who

was then in the beginning of his life-long professionalcarrier in pain, what was presumably one of the very

first multidisciplinary pain groups. Ulf Lindblom at that

time had started his pioneering work with developing

quantitative methods for testing cutaneous sensibility

(Lindblom, 1974) which later in collaboration with

Heinrich Frustorfer materialized in the so called QST-

system (Marstock�, stands for MARburg and

STOCKholm) (Frustorfer and Lindblom, 1984) whichhas been extensively used and accepted as a method for

accessing cutaneous thermal sensibility. In 1975 we

published in the third issue of Pain a paper describing

that SCS seemed to attenuate the perception of pain,

induced by pinching a fold of the skin with a flat cali-

brated forceps, only in regions exhibiting hyperalgesia

whereas the pain thresholds in normal skin were unaf-

fected (Lindblom and Meyerson, 1975). The thresholdsto mechanical innocuous stimuli in the form of a blunt

probe assessed in skin with normal sensibility were in-

creased during and after SCS and this effect was present

also on suprathreshold sensory functions (Lindblom and

Meyerson, 1976a). Also the perception of vibratory

stimuli was attenuated (Lindblom and Meyerson,

1976b) and that is conceivably the reason why some

patients report that the experience of paraesthesias inthe legs may interfere with walking. When mechanical

stimuli were applied to hypersensitive skin and perceived

as painful (allodynia), SCS markedly increased the

thresholds and suppressed the painful sensation. Similar

normalizing effects were found on abnormal thermal

al Association for the Study of Pain. Published by Elsevier Science Ltd.

366 B.A. Meyerson / European Journal of Pain 7 (2003) 365–367

sensibility (warmth, heat and cold) characterized by anabnormally narrow warmth–cold difference limen, de-

creased thresholds for perception of heat as well as of

cold; no effects could be recorded on thermal sensibility

when tested in regions outside the painful area. All these

effects of SCS occurred in parallel with the suppression

of spontaneous pain. The characteristic time course of

the SCS-effect with a long lasting post stimulatory sup-

pression both of tactile and thermal allodynia and ofhyperalgesia and as well as of spontaneous pain led Ulf

Lindblom to the conclusion that the mode of action of

SCS involves a central inhibitory state.

The finding that SCS does not seem to influence

normal perception of noxious stimuli was later chal-

lenged by the group of Marchand at Quebec University

who reported that the stimulation could alter the ratings

of cutaneous heat pain induced by a contact thermode(Marchand et al., 1991). They described that the heat

pain threshold was increased by �1 �C.The potency of SCS to suppress signs of neuropathy

was later further confirmed also in other forms of

stimulation of the nervous system. In the mid 1980s we

developed a technique of stimulating the Gasserian

ganglion and intracisternal trigeminal rootlets as

treatment of painful trigeminal neuropathy (Meyersonand H�aakanson, 1986). These patients frequently pres-

ent with abnormal trigeminal sensibility and several of

them were examined by Ulf Lindblom who demon-

strated that the hypersensitivity both to tactile and

thermal stimuli was effectively abolished. Later, in the

early 1990s, we started to treat such patients with

motor cortex stimulation. In contrast to other forms of

nerve stimulation, such stimulation does not produceany subjective sensations (paraesthesias) and therefore

it was for the first time possible to assess the outcome

in a double blind fashion (Meyerson et al., 1993).

When we tested the first patients who suffered from a

very prominent tactile allodynia and dysaesthesia cov-

ering the entire trigeminal territory, it happened that

Patrick Wall visited our department. He attended a

testing session and we could then for the first time alsoapply blinded stimulation (with an exhausted battery)

and confirm not only the efficient pain relief but also

the normalization of the exaggerated sensitivity to

brushing and touching the face.

In order to further explore the functional organisa-

tion of the neuronal substrate to SCS, Ulf Lindblom

also initiated a couple of studies on the characteristics of

spinal evoked potentials and their relationship to thegeneration of stimulation-induced paraesthesias (Hall-

str€oom et al., 1989, 1991).

It was obvious that Ulf Lindblom as a clinically ac-

tive neurologist with a background of basic research was

intrigued by the possibility of manipulating the spinal

cord sensory function by SCS. During a sabbatical at

Cornell University he conducted together with Daniel

Tapper and Szuszanna Wiesenfeld an experimental,electrophysiological study in cats in which the effect of

SCS on neural dorsal horn activity was explored

(Lindblom et al., 1977). Several earlier such studies had

been performed but this was the first which demon-

strated that an inhibitory effect of SCS in some of the

cells could outlast the stimulation for up to 10–30 min.

The authors rightly concluded that the otherwise mod-

erate effects of SCS on nociceptive neurons corre-sponded to previous observations of a retained

perception of acute pain during SCS in man. That latter

remark is of particularly importance since virtually all

experimental SCS-studies in the 1970s and 1980s were

performed on normal, intact animals, and therefore

their relevance for SCS-effects in patients with neuro-

pathic pain is limited.

Ulf Lindblom�s early observations of the differentialeffects of SCS on disturbed cutaneous sensibility in pa-

tients with neuropathic pain inspired us to use animal

models of mononeuropathy with the aim to further ex-

plore the mechanisms involved in the pain relieving ef-

fect of SCS. These rat models, of which there today exist

many varieties, typically exhibit signs of neuropathy in

the form of hypersensitivity to innocuous stimuli applied

to the hind paw after ipsilateral partial injury of thesciatic nerve. In fact, these disturbances of sensibility are

reminiscent of symptoms often present in patients suf-

fering from pain as a result of peripheral nerve injury,

and that is why these models have been extensively

utilized in experimental pain research. However, their

clinical relevance may be disputed since these rats do not

to any extent display behavioural aberrations indicating

the present of ongoing spontaneous pain. Therefore,they may, at best, be regarded to mimic only the evoked

pain components present in patients with nerve injury.

We developed a technique for applying SCS in awake

and freely moving rats with partial sciatic nerve lesion

(Linderoth et al., 1993) and studied the effects on the

‘‘evoked pain’’, i.e. abnormally low thresholds of paw

withdrawal in response to innocuous peripheral stimu-

lation. Care was taken to apply SCS with clinicallyrelevant parameters (intensity, duration of stimula-

tion, etc.). It was demonstrated that in a substantial

proportion of the rats the abnormally low thresholds to

mechanical stimulation (applied by von Frey filaments)

were almost or completely normalized as a result of SCS

and this effect outlasted the stimulation for up to one

hour (Meyerson et al., 1995). It was also found that in

acute experiments the hyperexcitability of dorsal hornWDR-neurons could be effectively suppressed by SCS

(Yakhnitsa et al., 1999).

These models of SCS and neuropathic ‘‘pain’’ have

proven to be most useful in a number of subsequent

studies aiming also at the exploration of transmitter-

receptor mechanisms possibly related to the mode of

action of SCS in neuropathic pain.

B.A. Meyerson / European Journal of Pain 7 (2003) 365–367 367

In recent years, much attention has been focused onthe possibly different mechanisms underlying the devel-

opment and maintenance of two forms of mechanical

allodynia: dynamic and static (Ochoa and Yarnitsky,

1993). The former is the clinically most common as as-

sessed at neurological bedside examination. There is

experimental evidence that the dynamic form of allo-

dynia is signalled via A�-fibres and mediated by the

dorsal columns while the static form may be transmittedvia sensitised C-fibres. However, the relaying of both

forms may involve the WDR-neurons. Most of Lind-

blom�s early experiments were performed with the use of

blunt calibrated mechanical pulses the exaggerated

perception of which may correspond preferentially to

the static form of allodynia. In some others, for example

in the test of the patient with motor cortex stimulation

referred to above, the trigeminal sensibility was testedwith a brush evoking dynamic allodynia. However, in

virtually all experimental studies performed on rat

models of mononeuropathy, static ‘‘allodynia’’ has been

examined and, to the best of my knowledge, the dy-

namic form, using brushing with a cotton pad, has been

examined only in one study (Field et al., 1999). Con-

sidering that the two forms of allodynia presumably are

mediated centrally via different pathways it would be ofcrucial interest to further examine a possibly differential

effect of SCS on allodynia in both patients and animal

models.

The similarity between the effects of SCS on signs of

neuropathy in the rats and on cutaneous sensibility ab-

normalities associated with pain following nerve injury

in patients is striking. That is the main reason why we

still consider our rat models to be ‘‘clinically relevant’’and therefore useful for the further exploration of the

mystery of a method for management of chronic pain

having the unique feature of providing relief that may

persist for decades without loosing its efficacy.

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