Blackwell Publishing IncMalden, USAPMEPain Medicine1526-2375American Academy of Pain Medicine?

200675
396407MiscellaneousISIS Position Paper on Pulsed RFBogduk

PA I N M E D I C I N E
Volume 7 Number 5 2006

Position Papers
Pulsed Radiofrequency

Nikolai Bogduk, MD, PhD, DSc

University of Newcastle, Department of Clinical Research, Royal Newcastle Center, Newcastle, New South Wales, Australia

Introduction cautery for hemostasis, ablation of aberrant car-

lthough the eventual focus of this position diac conduction pathways, and tumor ablation. In
A paper is on a procedure known as pulsed
RF, its earlier parts cover issues of terminology
the present article, the term qualies the nature of
an alternating electrical current used to treat pain.
and an overview of other applications of radiofre- This current has a frequency in that of the AM
quency (RF) current in Pain Medicine. Each of radio band (500,000 Hz).
these preliminary matters is germane to the even- Particular and distinct procedures are dened
tual consideration of pulsed RF. Terminology is by the nouns that follow, and by any additional
important because confusion can arise when unin- adjectives that precede the termradiofrequency,
formed individuals mistake certain procedures in their name. In general, the nouns pertain to the
with others because they share the termradio- desired effect that the procedure has in terms of
frequency; and there is evidence that such con- iatrogenic pathology. The adjectives are of two
fusion has arisen. Considering other clinical classes: those that qualify the physical nature of the
applications of RF current is important because it current or its physical effects, and those that
establishes benchmarks against which the evolu- describe the anatomical target (Figure 1).
tion and present status of pulsed RF can be Different procedures differ in critical respects.
compared. On the one hand, there have been Unless they are correctly and rigorously named,
procedures that have withstood scientic scrutiny. the properties of one procedure may be inferred
On the other hand, there have been procedures to apply to a different procedure when, in fact,
that have been promoted enthusiastically only to they do not. Indeed, the differences between
be refuted once strict scientic studies have been established procedures are substantial and more
conducted. The question that arises is where than clinically signicant. Those procedures share
pulsed RF lies in this spectrum. This article little in common save for the central word
addresses the current status of pulsed RF on the radiofrequency.
strength of available basic science and clinical
literature. History

Radiofrequency currents were originally used to

Terminology produce heat lesions in order to treat trigeminal
The adjectiveradiofrequency (RF)is cur- neuralgia. A needle electrode is placed in the
rently used to describe a variety of percutaneous trigeminal ganglion or its sensory root, and a heat
procedures used in medicine. In other disciplines, lesion is produced to destroy nerve cells in the
it qualies a type of energy used to create heat and particular division of the nerve that had been
achieve tissue necrosis. Examples include electro- mediating the patients symptoms. In full, the
procedure was called trigeminal (Gasserian) radio-
frequency ganglionotomy or rhizotomy. An additional
adjective to qualify the physics of the procedure
This position paper was commissioned by the International was not required, for it was implied that a thermal
Spine Intervention Society. It was prepared in 2004 and lesion was produced.
revised in October 2005 and again in January 2006. It has
been endorsed by the International Spine Intervention Percutaneous techniques utilizing RF currents
Society, the North American Spine Society, and the Amer- to destroy nerves were then developed to disrupt
ican Academy of Orthopedic Surgeons. the transmission of pain signals through the

American Academy of Pain Medicine 1526-2375/06/$15.00/396 396407

ISIS Position Paper on Pulsed RF
adjective adjective radiofrequency noun
trigeminal none ganglionotomy
cervical thermal cordotomy
lumbar partial neurotomy
thoracic pulsed rhizotomy
medial branch lesion
none
anatomical physical
Figure 1 The structure of terminology pertaining to radio-
frequency procedures used to treat pain.
anterior-lateral spinothalamic tracts of the spinal
cord. Percutaneous cervical RF cordotomy has typi-
cally been utilized to treat intractable cancer pain.
Radiofrequency currents were next applied to
treat spinal pain mediated by the medial branches
of the dorsal rami, and ostensibly stemming from
the zygapophysial joints. The procedure was orig-
inally called facet denervation, but was renamed
when it was established that the technique origi-
nally described did not necessarily denervate the
joint [1]. When performed accurately, the proce-
dure targets a medial branch (of a dorsal ramus),
and accordingly it was named medial branch radio-
frequency neurotomy [2,3].
Originally, an adjective qualifying the physics of
the procedure was not required, but in the light of
current developments, the term thermal needs to
be added. Accordingly, thermal medial branch
radiofrequency neurotomy is a procedure in which a
medial branch is coagulated by an RF current
delivered in such a manner to produce a heat
lesion in the target nerve.
The third development in the history of RF
therapy involved two changes. First, the target
became the dorsal root ganglion (DRG) of a spinal
nerve (cervical, thoracic, lumbar, or sacral). Sec-
ond, the intention was not to destroy the nerve
completely. Instead, a heat lesion was placed suf-
ciently near the DRG to produce what was
described as a partial lesion, but not so close as to
completely destroy the ganglion. The intention
was to produce a lesion that might relieve pain,
similar in concept to trigeminal RF rhizotomy, but
that nevertheless would not interrupt other sensa-
tions in the dermatome of the target nerve.
Accordingly, the procedure became known as
partial radiofrequency rhizotomy [4,5]. Later, it
became known as radiofrequency lesion adjacent
to the dorsal root ganglion [6]. This name was
contracted to radiofrequency-dorsal root gan-
glion, and abbreviated to RF-DRG [6,7].
397
Another feature of RF-DRG that distinguished
it from thermal medial branch RF neurotomy was
that a lower temperature was used. Whereas a
temperature of 8090C was typically used for
thermal neurotomy, that temperature was reduced
to 67C for RF-DRG. Ostensibly this change was
adopted in order to reduce the risk of side effects
due to denervation of the dermatome.
A pivotal study precipitated what was to become
the fourth, and most recent evolution of RF treat-
ment. Slappendel et al. [8] compared the outcomes
of cervical RF-DRG in patients treated with
lesions made at 40C or 67C. They found no
signicant difference. The investigators inter-
preted this result as indicating that 40C lesions
and 67C lesions were equally effective, and
inferred that the efcacy was due to an effect other
than a thermal lesion. A competing interpreta-
tionthat neither intervention was effective and
that all responses were due to a placebo effect
was not entertained.
The interpretation of equal effectiveness
prompted a search for an explanation of a mecha-
nism other than a heat lesion. The following
hypothesis emerged: irrespective of the heat pro-
duced, a radiofrequency current was therapeutic
because of electrical effects it had on the target
nerve, which gave rise to another mode of apply-
ing RF current.
It was believed that a therapeutic electrical
effect could be delivered without heating the nerve
and therefore without coagulating it. This is
achieved with brief bursts of RF energy separated
by relatively long pauses between bursts to allow
heat to dissipate in the target tissue, and became
the theoretical basis of what is currently known as
pulsed radiofrequency.
A conspicuous distinction of the term pulsed
radiofrequency is that it lacks a subject noun.
Explicitly, the procedure is not a neurotomy, for
no lesion is made. If a noun is required, it is no
more than treatment.
Thermal RF Neurotomy
Physics
To create a thermal lesion with monopolar RF, a
ground plate, with a large surface area is applied
to the body. A needle electrode is directed onto
the target nerve. The electrode is insulated along
its length, save for the tip for a distance of 2
10 mm. The ground plate and electrode are con-
nected to a generator. The tissues of the body
complete the circuit.
398
RF Generator
electrode
ground plate
Figure 2 A sketch of the circuitry and electric field of ther-
mal radiofrequency (RF) neurotomy. From the ground plate,
the electric field is concentrated onto the exposed tip of the
electrode.
The generator produces an alternating current
in the RF range. Delivered from the ground plate
across a large surface area, the electric eld con-
centrates onto the uninsulated tip of the electrode
(Figure 2).
The concentrated alternating electrical eld at
the exposed tip of the electrode oscillates charged
molecules in the intervening body tissues. The
oscillation is of greatest amplitude where the elec-
tric eld density is highest. The density is greatest
near the electrode, and here the oscillation of
charged molecules is most intense (Figure 3).
Molecular oscillation generates heat. When so
heated, tissues near the electrode will secondarily
transfer heat to the electrode, and that tempera-
insulated shaft
electric field lines
tip
E+
+E
o
65 C isotherm
Figure 3 Effects near the tip of the electrode subjected to
a radiofrequency current. Electric field lines converge onto
the tip of the electrode. Charged molecules oscillate with
the electric field (E). Temperatures are higher where the
electric field is denser. Isotherms radiate concentrically
from the surface of the electrode.
Bogduk
ture can be monitored if a thermocouple is
inserted into the electrode or incorporated into it.
If the amplitude of the applied current is
increased, the temperature achieved in the tissues
will increase. At increasing distances from the
electrode, the temperature achieved will be pro-
gressively less, in proportion to the decreasing
density of the electric eld. In effect, isotherms
can be identied in a concentric pattern extending
from the electrode (Figure 3).
From laboratory studies [9,10], it appears that
most soft tissues coagulate if they are heated above
6065C. If a temperature of 8085C is estab-
lished at the surface of the electrode, tissues within
a few millimeters of the electrode will be heated
to 6065C or more. At that temperature the tis-
sues are coagulated, i.e., denatured. The actual
distance at which these temperature thresholds are
reached differs according to the physical charac-
teristics of the electrode; but as a rule of thumb,
tissues within about two electrode-widths from the
surface of the electrode will be coagulated. Fur-
thermore, the surrounding tissue is coagulated in
the form of a prolate spheroid, whose long axis is
formed by the uninsulated tip of the electrode
(Figure 4). Because the electrode coagulates trans-
versely, not distally, the electrode must be placed
parallel to the target nerve in order for the lesion
to be optimally effective [10].
ELECTRODE
SMK RRE
w 0 .7 m m 1.6 m m
r 2 .3 w 1.6w
sd 0.4 w 0 .3 w
d 1 .4 w 0.4w
sd 0.4 w 0 .2 w
w
Figure 4 The geometry of the lesion generated by a ther-
mal radiofrequency current. The volume of tissue coagu-
lated assumes the shape of a prolate spheroid, i.e., elliptical
in longitudinal section and circular in transverse section.
The radial extent (r) of the lesion beyond the surface of the
electrode and its distal extent (d) beyond the tip of the
electrode are functions of the width (w) of the electrode.
The inset shows the actual dimensions of lesions generated
by two types of electrodes [9,10]. SMK, RRE = electrode
types manufactured by Radionics Inc., Burlington, MA.
ISIS Position Paper on Pulsed RF
Pathology
If the electrode is placed sufciently close to a
target nerve, that nerve will be incorporated into
the lesion formed around the electrode. If an elec-
trode is inserted into a DRG, heating it to 67C
produces a hemorrhagic lesion with total loss of
myelinated bers [11]. If a large electrode (14G)
is placed beside a DRG, thermal lesions of 45C,
55C, 65C, 75C, and 85C produce total loss of dotomy has similarly been established in patients
unmyelinated nerve bers and near total loss of
myelinated bers [12]. In the sciatic nerve, an
80C thermal lesion produces extensive Wallerian
degeneration of the axons, and disruption of their
myelin sheaths and epineurium [13]. In the saphe-
nous nerve, lesions made at 70C destroy both
myelinated and unmyelinated bers [14].
Physiology
An early study claimed that RF coagulation selec-
tively destroyed on A and C bers and hence
could be selective for preventing nociception [15].
This contention, however, has not been borne out
by subsequent experiments, and is incompatible
with the pathology data, which show that RF
coagulation affects all nerves, myelinated and
unmyelinated. EMG studies have shown that even
alpha motor neurons are coagulated [16]. RF neu-
rotomy, therefore, is a nonselective method of
coagulating nerves.
Technique
The technique of thermal RF neurotomy requires
accurate placement of the electrode onto the tar-
get nerve. In the case of medial branch neurotomy
for spinal pain performed under uoroscopic
guidance, the electrode must be carefully juxta-
posed parallel to the target nerve. Once it has been
placed, the position of the electrode must be held
in place while the surrounding tissue temperature
is increased to the operating temperature and
maintained until thermal equilibrium is achieved.
Typically, this equilibrium occurs after 60 seconds.
Ideally, lesions must be made in several locations
along the course of the target nerve in order to
accommodate possible variations in the exact
actual location of the nerve. These requirements
render the procedure of thermal RF neurotomy
time-consuming and relatively arduous. Between
1 and 2 hours operating time may be required to
thoroughly coagulate two target nerves [17,18].
These features are pertinent because other RF
procedures are rendered attractive by promising a
substantially shorter operating time.
399
Efficacy
Thermal RF neurotomy has an established repu-
tation of efcacy for the treatment of trigeminal
neuralgia. Numerous descriptive studies have
recorded complete pain relief in up to 80% of
patients treated, with follow-up periods in excess
of 1 year, and in some studies, up to 11 and
14 years [19,20]. The efcacy of cervical RF cor-
with pain of neoplastic origin, although the suc-
cess of cervical RF cordotomy for nonmalignant
pain has been less encouraging.
When applied to peripheral nerves, thermal RF
neurotomy has been rigorously tested only when
the target nerves have been the medial branches
of the lumbar or cervical dorsal rami.
Although there is an abundant literature on a
procedure that was called lumbar facet denerva-
tion, most of these reports were awed as a
suboptimal surgical technique was employed.
Electrodes were either placed nowhere near the
target nerve or they were not placed parallel to
them [19]. It transpires that there is very little
literature on the efcacy of lumbar, thermal RF
neurotomy. What little there is, however, is sup-
portive. A placebo-controlled trial showed that the
effect of thermal neurotomy could not be attrib-
uted to placebo [21]. A descriptive study, which
used an anatomically accurate technique was uti-
lized, showed that 60% of patients maintained at
least 80% relief of pain for 12 months, and 80%
of patients maintained at least 60% relief for this
period [16]. Another outcome study showed that
if pain recurs, relief may be successfully reinstated
by repeating the neurotomy [22].
For cervical thermal RF neurotomy, the litera-
ture is stronger. A placebo-controlled trial showed
that the effects of cervical medial branch neurot-
omy were genuine [18]. Follow-up studies showed
that the median duration of complete relief of pain
was over 400 days, and that if symptoms recurred,
relief could be reinstated by repeat neurotomy
[17,23]. Thermal RF neurotomy of the third
occipital nerve successfully relieves cervicogenic
headache stemming from the C2-3 zygapophysial
joint [24]. The efcacy of cervical medial branch
neurotomy is not signicantly different in patients
with pending litigation and those not subject to
litigation [17,2325].
Signicant features of the literature on medial
branch neurotomy are the magnitude and duration
of effect. For lumbar medial branch neurotomy,
the benchmark is 80% relief of pain or greater
400
sustained for 12 months. For cervical medial
branch neurotomy, it is complete (100%) relief of
pain sustained for 1 year. Complete relief, not par-
tial relief, is the benchmark.
Intradiscal Thermal RF
The conventional application of thermal RF
requires placing the electrode onto the target
nerve, so as to incorporate that nerve into the
small lesion produced by the electrode. A depar-
ture from this paradigm arose when thermal RF
was used to treat discogenic low back pain. The
origin of this departure is difcult to trace. Inves-
tigators who subsequently studied the procedure
[26,27] referred to various personal communica-
tions and unpublished sources dating to 1994.
Intradiscal RF involved placing the tip of the
electrode into the center of the nucleus pulposus
of the target disk. It was recognized that the lesion
produced in this location did not coagulate nerves,
for the nucleus pulposus is devoid of nerves. How-
ever, proponents argued that the electric eld pro-
duced around the electrode was sufcient to heat
and destroy nerve bers in the outer anulus bro-
sus, and thereby provide relief of pain. This belief
was based on a theoretical assessment of the mag-
nitude of the electric eld and the proposition that
temperatures of 45C would be achieved in the
outer anulus, and would be enough to coagulate
nerves.
Cadaver studies rapidly dispelled this notion
[26,28]. Signicant heating did not occur in the
outer anulus. Nevertheless, the procedure contin-
ued to enjoy some popularity in some circles.
A controlled trial eventually demonstrated that
intradiscal RF achieved no greater relief of pain
than sham therapy [27]. What were promoted as
successful outcomes in earlier observational stud-
ies [29] amounted to no more than placebo
responses. A later study showed no gain in out-
come when an 80C lesion maintained for
360 seconds instead of 120 seconds [30]. Although
patients reported substantial reductions in pain
immediately after the procedure, those results rap-
idly attenuated until baseline pain scores were
restored at 2 months.
RF-DRG
Rationale
Proponents of RF-DRG believe that a therapeutic
effect may be achieved by a partial nerve lesion pro-
Bogduk
duced in the DRG. Explicitly, they have stated that
it is not the intention of this procedure to coagulate
the entire ganglion. Rather, the procedure is
intended to expose the dorsal root ganglion to tem-
peratures that prevail in the peripheral part of an
RF lesion to preserve the large myelinated bers
and to deactivate the small myelinated bers [31].
Critics are perplexed by the inherent paradox in
this rationale: the DRG is referred to as the target
but the lesion must not be so close as to actually
cause signicant damage to the target [32]. The
literature [15] cited by the proponents [31] as evi-
dence of a differential effect on small diameter and
large diameter afferents has been refuted [14].
This paradox invites the interpretation that per-
haps the lesion does nothing to the nerve, and the
outcomes are due to no more than a placebo effect.
This paradox is reected in the empiric clinical
data.
A morphological study in goats showed that
DRG-RF produced no destructive changes in the
nerve, provided that the electrode was placed adja-
cent to the ganglion [11]. If placed within the
ganglion, the lesion destroys myelinated bers [11].
Efficacy
The outcomes of RF-DRG are not consistent
across cervical [4,7], thoracic [5,6], and lumbar
[33,34] applications. The outcomes of cervical RF-
DRG are less than modest, even in a controlled
trial. For lumbar RF-DRG, a rigorous controlled
trial has shown that sham therapy achieves at least
equivalent outcomes to those of active therapy.
Thoracic RF-DRG has not been subjected to a
controlled trial, but it might be effective for cer-
tain types of thoracic pain for which there is not
an analog at cervical and lumbar levels [5,6]. The
available data hint at the possibility that thoracic
RF-DRG could be useful for postsurgical pain [5],
although not for neuralgias [6].
Pulsed RF
Introduction
It is not evident from their publication why Slap-
pendel et al. [8] undertook to compare the effects
of 40C and 67C RF-DRG. Their article simply
announces that the study was performed. Table 1
summarizes their results.
These data are remarkable for two features.
First, between groups there is no signicant dif-
ference at any time. Within groups, there is an
initial decrease in pain scores, but the decrease is
ISIS Position Paper on Pulsed RF
Table 1 The results of RF-DRG at two different tempera-
tures [8]
Group 1:
67C
Number 32
VAS (010)
baseline 6.7 1.6
6 weeks 4.8 3.5
3 months 5.0 2.9
Number with VAS: 01 at 3 months 4 3
RF-DRG = radiofrequency-dorsal root ganglion; VAS = visual analog scale.
not signicant clinically, for it is less than the 2-
point change that is considered the minimal
detectable change.
Second, an ambivalent observer could reason-
ably conclude that neither approach offered any
signicant benecial effect, i.e., they were both
equally ineffective. The fact that a small fraction of
patients from both groups of patients (12% and
10%) had low pain scores at 3 months could be
dismissed as a placebo response. This pattern of
response would be expected from two interven-
tions that each had no true biological effect. Thus,
the results do not warrant a critical appraisal of
the mechanisms and the mode of action of radio-
frequency lesions, which was the conclusion of
the authors; particularly when earlier studies of
RF-DRG had also not shown any convincing ther-
apeutic effect.
Theory
The theory of pulsed RF is that the tip of the
electrode delivers a large current density, esti-
mated as 2 104 A/m2 [35]. This current can be
applied to a nerve, without heating it, and without
creating a histological lesion, by delivering the
current in very brief pulses. The recommended
protocol involves delivering a current of
50,000 Hz in 20-millisecond pulses, at a frequency
of 2 per second (Figure 5). By limiting the delivery
of current in this manner, the relatively long pause
between pulses allows any heat generated to dissi-
pate and thereby prevent the development of any
thermal lesion. Heat is further minimized by lim-
iting the electrode tip temperature to less than
42C. Meanwhile, the electrical current, and its
purported therapeutic effect, is delivered to the
nerve.
As the greatest density of the electric eld is
near the tip of the electrode (Figure 3), the applied
current is densest distal to the tip of the electrode.
This rationale allows the electrode to be applied
perpendicular to the target nerve.
401
Pathology
Studies have explicitly examined the pathological
Group 1: effects of pulsed RF in laboratory animals. In one
40C
study, neither continuous RF nor pulsed RF, at
29 42C, produced any lasting effects on a DRG [13].
6.3 2.1
Both types of treatment produced edema at 2 days,
4.9 2.7 which was resolved by 21 days; but the DRG cells
4.4 2.9 remained structurally normal. Similar effects were
observed when the same lesions were applied to a
sciatic nerve [13].
In another study, no structural lesions were
found on light microscopy, following application
to a DRG of either a continuous RF current at
67C, or a pulsed RF current at 42C [36]. Elec-
tron microscopy, however, did show some
changes. In the ganglia treated with continuous
RF at 67C, DRG neurons exhibited numerous,
giant cytoplasmic vacuoles fused with each other,
and enlarged endoplasmic reticulum cisterns; in
some cells, there was loss of integrity of nuclear
and neurolemma membranes. In the ganglia
treated with pulsed RF at 42C, enlargements of
endoplasmic reticulum cisterns were observed,
along with some vacuole groups, in DRG cells, but
membranes were intact. Following either treat-
ment, myelinated and unmyelinated nerve bres
remained normal in morphology.
These morphology studies corroborated the
inference from the physiology studies: that pulsed
RF does not produce a lesion in the nerves treated.
Physiology
The pulsed RF theory explicitly maintains that no
lesion is created in the nerve [35]. The fact that no
histological lesion (axontomesis or neurotemesis)
10 s
20 m s
0.5 s
Figure 5 The parameters of a pulsed radiofrequency
current [35].
402
is created has been borne out by laboratory
studies.
A study that predated the concept of pulsed RF
showed that applying a continuous RF current to a
peripheral nerve, with a tip temperature of 40C
to 45C, resulted in reversible conduction block in
the nerve [37]. Upon cessation of the current, con-
duction promptly reverted to normal. Brodkey
demonstrated that the same effect was achieved by
heating the nerve using water circulated through
a coil around the nerve [37].
Thus, heating a nerve to low temperatures (40
45C) temporarily blocks conduction along the
nerve, but the rapid recovery of function indicates
that no physiologic lesion is produced. These
experiments do not exclude a possible induced
electrical effect of RF current, but the fact that
heated water achieved the same effect strongly
suggests that it is the low level of heat produced,
not the current itself, which was responsible for
the temporary conduction block.
In a study using slices of hippocampus as the
target tissue [38], two protocols of pulsed RF
(one at 38C and one at 42C) and a 42C continu-
ous (thermal) RF current were applied for
120 seconds. The continuous current reduced
excitatory postsynaptic potentials (EPSPs) to less
than 50% of normal amplitude, for the duration
of the experiment (25 minutes). The 38C pulsed
RF reduced EPSPs to 75% normal amplitude for
ve minutes after application. Thereafter, normal
amplitudes recovered. The 42C pulsed RF
reduced EPSPs to 50% normal amplitude for
5 minutes. Thereafter, normal amplitudes
recovered.
Beyond 2,000 m from the electrode, neither of
the pulsed RF protocols produced any lesions in
the tissue; neither did the continuous thermal pro-
tocol. Between 500 m and 1,000 m, tissue dam-
age occurred with the thermal protocol but not
with either pulsed protocols. Within 500 m, all
protocols all produced tissue damage.
These results show the expected effect of even
a low temperature continuous RF thermal RF
lesion. Tissues were coagulated to a distance
slightly greater than one electrode-width from the
surface of the electrode (1 mm). This coagulation
was consistent with marked reduction in function
of the affected tissues (EPSP > 50% reduced for at
least 25 minutes).
In contrast, both pulsed RF protocols produced
only a minimal lesion immediately around the sur-
face of the electrode (<0.5 mm). Although neural
function was suppressed, the effect was only tran-
Bogduk
sient (5 minutes), which is consistent with no sig-
nicant permanent lesion having been made.
A third study examined the effects on cells in
the dorsal horn of the rat spinal cord following
pulsed RF application to the C6 DRG [39]. The
C6 DRG was exposed to continuous RF or pulsed
RF at 38C. The animals were sacriced 3 hours
after exposure, and immunohistochemical assays
for c-fos reactivity performed. Animals treated with
pulsed RF at 38C exhibited increased expression
of c-fos in lamina I and lamina II. These effects
were not seen in animals treated with continuous
RF at 38C.
These results indicate that pulsed RF activates
sensory bers in the DRG and the spinal neurons
to which they relay. The clinical implications of
this nding are not known. The duration of
changes in dorsal horn c-fos are not known, as
animals were sacriced 3 hours after RF exposure.
The fact that continuous RF did not produce
changes in dorsal horn c-fos indicates that it is not
electrode current itself but its delivery in pulses
that is responsible for the effect.
Somewhat contrary results were obtained in
another study [40]. It examined the effects on dor-
sal horn cells of both continuous and pulsed RF
applied to the C6 DRG compared with sham
treatment. Both forms of RF application induced
increased c-fos expression in the dorsal horn. This
contradicts a specic effect attributable to the
delivery of current in pulses.
Collectively the results of these studies provide
extremely limited insight into the potential phys-
iological effects of pulsed RF. The study of Brod-
key et al. [37] did not address the effects of pulsed
RF; but it established a reference point. Heating a
nerve temporarily blocks conduction along it.
This is compatible with the effects observed by
Cahana et al. [38] caused by a continuous 42C RF
lesion, but not pulsed RF at 38C or 42C.
In contrast to continuous RF lesions, pulsed RF
seems to have limited effects. It transiently sup-
presses, but does not abolish, EPSPs in tissue
slices [38], and also seems to activate a subset of
central spinal cord neurons [39]. Specically, how-
ever, pulsed RF does not produce a tissue lesion.
Any therapeutic effect, therefore, would seem to
be akin to a brief and mild electrical stimulation,
perhaps not unlike the effects of a brief application
of transcutaneous nerve stimulator or an im-
planted nerve stimulator.
The ndings that pulsed RF, and continuous
RF for that matter, increase expression of c-fos do
not provide an explanation for the effects of RF.
ISIS Position Paper on Pulsed RF
Expression of c-fos is no more than a marker of
increased cellular metabolic activity; it is not even
specic for nociceptive pathways. It indicates only
that cells are activated. It does not distinguish
between inhibitory and excitatory activity. It is not
evidence that patients will be relieved of their pain.
For such reasons, an editorial [41] concluded that
. . . basic scientic studies in the neurobiology of
pain models and analgesic techniques are not a
substitute for randomized controlled clinical trials,
and studies such as that of van Zundert et al. [41]
do not justify using the technique clinically.
A revised theory has sought to convert the orig-
inal, purely electrical model into a thermal one
[42]. The theory proposes that, during each pulse,
the electrode is heated temporarily, and that this
heat is responsible for the therapeutic effect. An
accompanying study, using nite-element model-
ing, explored the magnitude of this effect. It
showed that the point of the electrode did, indeed,
produce heat. However, the range of inuence was
limited. Heat was generated at 0.3 mm from the
tip, but was proportional to the intensity of stim-
ulation. Large increases in temperature occurred
only at voltages well above those commonly used
in practice. Meanwhile, the theory also still holds
out that the electric eld of pulsed RF might depo-
larize and disrupt nerve cell membranes.
Efficacy
Clinical data on the efcacy of pulsed RF are
extremely limited. The worldwide popularity of
pulsed RF treatment is severely disproportionate
to the volume and quality of the available litera-
ture and the efcacy that it describes.
One publication [35] reports two briey
described studies. In the rst, patients were treated
with either pulsed RF or continuous RF applied
to a DRG. The anatomical location of the target
nerve (cervical, lumbar) was not given. Both forms
of RF were delivered at 42C. Table 2 shows the
results at 6 weeks. No other outcome measures
were provided.
Table 2 The reported results of pulsed radiofrequency
treatment [35]
Global Perceived Effect
N (%)
Treatment N >75% 5075% <50%
Continuous RF 24 1 (4) 2 (8) 21 (88)
Pulsed RF 36 20 (56) 11 (30) 5 (14)
RF = radiofrequency.
403
The effects of continuous RF were poor.
Indeed, the authors commented that they aban-
doned this intervention because of the high failure
rate [35]. This appraisal of continuous RF is at
direct odds with how Slappendel et al. [8] por-
trayed their outcomes with the same procedure.
Slappendal et al. [8] considered their meager out-
comes with 40C RF-DRG to be sufcient to war-
rant exploration of the mechanism by which it was
therapeutic; which in turn was the step that gave
rise to pulsed RF. It is clearly ironic, therefore, that
Sluijter et al. [35] found and considered the results
of the identical procedure to be so poor as to
warrant abandonment.
Meanwhile, results of pulsed RF in this study
were obviously better, at least at 6 weeks. Unfor-
tunately, the report of outcomes was severely lim-
ited. Global perceived effect is not the same as
relief of pain; and no other outcome measures
were provided. Nor was there any longer-term
follow-up. At best, it might only be deduced from
this study that pulsed RF offers a short-term ben-
et to some patients with radicular pain.
The second study [35] involved 20 patients
with persistent leg pain after surgery. Five were
excluded because they did not respond to diagnos-
tic blocks. Of the 15 remaining, eight were said to
have obtained a satisfactory result, dened as a
greater than 2-point improvement in pain scores
(range: 24), at 6 months after treatment. Two of
these had a recurrence between 6 and 12 months.
The fate of the others was not reported.
This denition of success is somewhat gener-
ous, and the sample-size is small. Although these
data suggest some degree of benet, the results
cannot be attributed to pulsed RF, for no controls
were used.
A case report [43] ventured that pulsed RF of
the sphenopalatine ganglion relieved a patient of
posttraumatic headache. That report, however,
did not provide data by which to distinguish the
effects of pulsed RF from those of the local anes-
thetic and corticosteroids that were injected onto
the ganglion at the time of operation.
In another study [44], the target for pulsed RF
was not a DRG but the medial branches of the
cervical and lumbar dorsal rami. Here, the authors
reported that 68 of 114 patients (60%) obtained
at least 50% relief of pain for a minimum of
1.5 months. On average, the relief lasted
3.9 1.9 months.
These results paint a modest picture of the ef-
cacy of pulsed RF delivered to the medial
branches. No patients were rendered pain-free,
404
and relief persisted for only a very short period.
There was no control group. Recall that the
benchmark set by cervical RF thermal neurotomy
is complete relief, and for lumbar RF thermal neu-
rotomy, 80% relief, sustained for 1 year.
Thus, it is not evident if the observed outcomes
from the aforementioned studies could be attrib-
uted to the pulsed RF. For relief that is moderate
in magnitude and limited in duration such as those
reported by Mikeladze et al. [43], controls are
essential in order to exclude nonspecic treatment
effects. For reference, Marks et al. [45] found that
21% of their patients reported good relief con-
tinuing at 1 month, and 14% at 3 months, simply
after undergoing anesthetic medial branch blocks.
An audit of selected patients introduced an
additional indication [46]. The authors described
18 patients, with chronic neck and arm pain, who
were selected for treatment if they obtained at
least 50% relief of their pain following diagnostic
segmental nerve blocks. They underwent pulsed
RF of the DRG of the previously anesthetized
nerve. Of these patients, 13 reported greater than
50% improvement at 68 weeks, diminishing to
10 by 311 months, and six at 1 year. The authors
were guarded in their discussion. They wrote that:
this clinical audit . . . does not allow us to draw
denitive conclusions. Nevertheless, they offered
that the results justify the start of a randomized
controlled trial.
A recent study attests to a major departure from
the paradigm and application of pulsed RF. It pro-
motes intradiscal pulsed RF for the treatment of
discogenic pain [47]. The electrode is placed in the
center of the nucleus pulposus, where no nerves
are present.
The study described outstanding outcomes
in eight patients with discogenic pain, six of
whom were followed for 1 week, and ve for
625 months. No controls were used.
The mechanism of effect is dissonant with any
of the theories of pulsed RF. It cannot be attrib-
uted to an electric eld effect on nerves in the
vicinity of the electrode-tip. It cannot be attrib-
uted to pulsed heat, within 0.3 mm of the elec-
trode, as proposed by the revised theory of pulsed
RF [42]. Rather, the purported mechanism is a
remote effect of the pulsed electric eld on nerves
in the outer anulus.
Discussion
There are stark differences between thermal RF
lesioning techniques and pulsed RF treatment.
Bogduk
These approaches differ not only in the quality
and quantity of literature available, but with
respect to mechanism, rationale, and outcomes.
For thermal RF neurotomy, there is a strong
biological basis. RF current is used to heat tissue,
which subsequently results in a pathologic, histo-
logically veriable tissue lesion, and there is no
dispute of this being the objective of the proce-
dure. There is strong evidence of outcome, not
only with respect to relief of pain [16,1719,
23,24] but also in terms of restoration of function
[1618,23,24], and even resolution of psychologi-
cal distress [48]. The procedure has been vindi-
cated by placebo-controlled trials [18,21]. The
relief of pain from properly performed RF neuro-
tomy is profound. The benchmark is total relief of
pain [17,18,23,24] or nearly so [16]. The nominal
duration of relief is 1 year [1618,23]. Although
pain may recur in some patients as the peripheral
nerve regenerates, relief can be successfully rein-
stated by repeating the neurotomy [17,18,2224].
What is clearly evident from the literature is
that pulsed RF does not produce a lesion [38].
Therefore, pulsed RF cannot be represented as a
procedure resulting in nerve destruction, neurot-
omy, axontomesis, neurotemesis, gangloionolysis,
rhizotomy, or any other noun connoting tissue
damage or destruction. In this respect, pulsed RF
is clearly a different procedure from thermal RF.
The differences between thermal RF and
pulsed RF are as follows:
Pulsed radiofrequency is not equivalent to ther-
mal radiofrequency. It is not a substitute for thermal
radiofrequency in conditions for which thermal
radiofrequency has an established and proven
efcacy. There is no evidence that pulsed radio-
frequency replicates the efcacy of thermal radio-
frequency. The available data indicate that pulsed
radiofrequency is markedly inferior in these
instances [44].
If pulsed radiofrequency is misrepresented as the
same procedure or an equivalent alternative to ther-
mal radiofrequency, the inferior outcomes of the
former may likely be misattributed to the latter.
(This has already happened in Switzerland where
insurers had imposed bans on reimbursements for
any type of radiofrequency treatment because of the
poor outcomes of pulsed radiofrequency [49]).
Pulsed RF is an attractive procedure on several
counts. It is simpler than thermal RF. Electrodes
can be introduced in the same manner as needles
are used for diagnostic blocks; they do not need to
be positioned laboriously and meticulously as is
required for thermal RF. Because accurate place-
ment of electrodes is not critical, this also renders
pulsed RF a faster procedure than thermal RF. It
would not be surprising, therefore, if some prac-
ISIS Position Paper on Pulsed RF
titioners have adopted pulsed RF simply because
it is a quicker, easier procedure.
Observer bias is probably another factor. Prac-
titioners who adopt the procedure are likely to
remember their successful cases, but forget the
failures. Moreover, their impressions of the effec-
tiveness of the procedure are likely to be based on
immediate responses or short-term follow-up at
best. They are unlikely to be aware of the attenu-
ation of effects over time. Under those conditions,
a procedure with fair to reasonable short-term
outcomes may look attractive. Only when long-
term follow-up is conducted does the true effec-
tiveness, or lack thereof, emerge.
Another factor that attracts practitioners to
pulsed RF, especially those who have limited clin-
ical experience or technical skill in percutaneous
interventions, is the purported reduction or avoid-
ance of side effects and complications associated
with thermal RF, as the intent of pulsed RF is spe-
cically not to cause tissue injury. As no injection is
performed, pulsed RF treatment also purports
avoidance of potential complications associated
with intravascular or intraneural injections of local
anesthetics or particulate corticosteroids.
The nal attraction is nancial. Pulsed RF
becomes very attractive if it carries the same reim-
bursement code as thermal RF. For less effort, less
risk, and less time, practitioners get paid the same.
Therefore, practitioners and administrators
alike should distinguish pulsed RF and thermal RF
from one another.
The two procedures differ in mechanism and
effect:
Thermal RF produces a tissue lesion; pulsed RF
does not.
Thermal RF neurotomy has proven efcacy;
pulsed RF does not.
Using pulsed RF instead of thermal RF, where
the latter is indicated, denies the patient the
benet of a proven procedure in favor of an
unproven one.
Portraying pulsed RF as equivalent to thermal
RF neurotomy risks the poor outcomes of the
former procedure tarnishing the reputation of
the latter.
Mistaking the poor outcomes of pulsed RF as
an index of the efcacy of thermal RF neurot-
omy unjustly impugns what should be an effec-
tive procedure, if performed correctly.
For such reasons, responsible practitioners of
thermal RF neurotomy must dissociate themselves
from pulsed RF, until such time as compelling data
405
of efcacy become available. Health care adminis-
trators must also understand that pulsed RF and
thermal RF are different, nonequivalent proce-
dures, having differing outcomes, and involving
different degrees of medical risk, physician time
and training.
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