Pulsed Radiofrequency Current in the Treatment of Pain

Critical Reviews™ in Physical and Rehabilitation Medicine, 23(1–4), 213–240 (2011)
Pulsed Radiofrequency Current in the
Treatment of Pain
Justin Hata,1* Danielle Perret-Karimi,1 Cecil DeSilva,1
Daniel Leung,2 Naomi Betesh,3 Z. David Luo,1 Segun Dawodu,5
Karin Sinavsky,1 O. Jameson Stokes1 & Steve English1
Department of Physical Medicine and Rehabilitation, University of California, Irvine, Orange,
California; 2Department of Physical Medicine & Rehabilitation, University of Michigan, Ann Arbor,
MI; 3Department of Physical Medicine & Rehabilitation, The Mount Sinai Medical Center, New York,
NY; 4Albany Medical Center, Department of Pain Medicine, Albany, New York 5Albany Medical
College, Albany, New York
*Address all correspondence to: Justin Hata, Department of Physical Medicine and Rehabilitation, University of
California Irvine, 101 The City Drive, Bldg 53, Room B-3, Rte 81, Orange, CA 92868; [email protected]
ABSTRACT: The objective of this article is to explore the validity of the concept behind
the application of pulsed radiofrequency (PRF) current in the treatment of pain. Included are the potential mechanisms of action, a review of animal and clinical studies, and a
comparison of PRF clinically, when available, to traditional radiofrequency.
The antinociceptive effects of PRF are independent of temperature; PRF current
reversibly and selectively disrupts impulse transmission in small unmyelinated pain fibers,
and several mechanisms of action may play a role. There are few animal studies available
but they confirm improvement of both thermal hyperalgesia and mechanical allodynia
and show that the analgesic effect of PRF involves enhancement of descending noradrenergic and serotonergic inhibitory pathways.
In the clinical treatment of facet-mediated pain, the magnitude and duration of the
PRF effect seems to be less than that of conventional radiofrequency. For radicular pain,
50% to 70% response rates are noted for 2–4 months after PRF; an efficacy similar to that
of radiofrequency. Overall, despite the accumulation of a large amount of observational
data supporting PRF, there are still few randomized, controlled, double-blind trials. A
review of reported applications of PRF, however, is provided here to enumerate the potential indications of PRF.
To eliminate nonspecific treatment, control groups are critical in study design; sham
and standard of care controls should be considered. Future studies should include in
particular both short-term (<6 months) and long-term (6–12 months) follow-up intervals
to establish the true efficacy of PRF. A greater body of basic science, animal, and clinical
study data is imperative to establish further validation of this concept.
KEY WORDS: pain, chronic pain, pulsed radiofrequency, dorsal root ganglion, facet joint, cervical, lumbar,
radiculopathy, trigeminal neuralgia, intra-articular, joint neuralgia, neuropathic pain, neuromodulation
ABBREVIATIONS: ATF3, activating transcription factor 3; CRPS, Complex Regional Pain Syndrome; DRG, dorsal root ganglion; GPE, Global Perceived Effect; NRS, Numeric Rating Scale; PRF,
pulsed radiofrequency; RF, radiofrequency; VAS, Visual Analog Scale
2151-805X/11/$35.00 © 2012 by Begell House, Inc.
Hata et al
In the management of chronic pain, the ability to ablate or modulate sensory nerve fibers to cause analgesia has intrigued physicians for many years. Chronic pain is rarely
controlled with pharmacologic agents alone. Even multimodal therapy—combining
physical or occupational therapy, physical modalities, psychological interventions,
and interventional procedures—may be suboptimal1 in providing adequate analgesia.
Pulsed radiofrequency (PRF) is an available pain treatment modality that, despite a
lack of solid evidence, continues to be used among providers. Clinical applications of
PRF are growing and include the treatment of cervical and lumbar facet joint pain,
cervical and lumbar radicular pain,2 sacroiliac joint pain,3 trigeminal2,4 and other
neuralgias,5–10 myofascial pain,11 and intra-articular pain.12 Given its current uses, a
review of all available PRF literature is needed. The purpose of this review is to provide readers with updated information regarding the science of PRF by highlighting
basic science, animal study, and clinical data and to explore further the validity of the
concept behind the application of PRF in the treatment of pain. There is limited data
on how PRF treatment directly compares with continuous (conventional) radiofrequency (RF) ablation; however, 4 studies are reviewed in Table 1.
The application of RF current to sensory fibers has its beginning in 1974, when RF
was used to create a thermal nerve lesion for the treatment of trigeminal neuralgia.17
Shealy18 first initiated the use of RF as a treatment option for spinal pain in the early 1970s. During initial use, RF was applied percutaneously19 to sensory spinal nerve
roots. A controlled thermal lesion that would safely interrupt afferent spinal pathways
was the presumed result20 of RF. Early RF entailed the production of current through
electrodes to produce a thermal lesion and it was thought that heat would selectively
destroy C fibers. Brodkey et al.21 demonstrated that RF probe temperatures higher than
45°C caused tissue destruction. Letcher and Goldring22 noted that the only selective
destruction of small pain fibers in the lesion was found at the lesion periphery, where
the temperature was lower and where larger sensory and motor fibers were uninjured.
This was substantiated in 1981 by the findings of Smith et al.,23 who reported uniform
fiber damage for lesions caused by RF probe temperatures between 45 and 75°C. PRF
avoids uniform fiber damage. This is accomplished by applying the RF currents in a
pulsatile manner with cooling periods (of about 480 ms) separating the heating periods
(of about 20 ms), allowing for the heat to dissipate adequately.20 Sluijter et al.24 first performed PRF in 1998. In the current method of PRF application, the tip of the electrode
delivers a large current density of about 20,000 A/m2. This current is applied in brief
pulses at a usual protocol of 50,000 Hz in 20-ms pulses at a frequency of 2 per second.
The electrical current, with its associated therapeutic effect, is delivered at the tip of the
electrode where the greatest density of the electrical field is available to target the nerve.25
The temperature if the electrode tip is set not to exceed 42°C.24
Critical Reviews™ in Physical and Rehabilitation Medicine
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Tekin et al.14
Erdine et al.13
The decrease in the RF scores was
maintained for 6 months; this was not
the case for the PRF scores. At 1 year,
VAS scores were lowest in the RF
PRF, n = 20
Study duration: 12 months
RF, n = 20;
Sample size: sham, n = 20;
All 3 groups had higher mean VAS and
OSW scores before than after the procedure. PRF and RF VAS and OSW
scores were lower than the control
scores after the procedure.
The RF group reported significant pain
relief. There was no significant pain
relief in the PRF group. Only 2 patients
were able to discontinue pain medications. Three months after the procedure, all patients who received PRF
required ongoing medical treatment
and still reported pain. All patients
in the PRF group then received RF
ablation; VAS scores in this group then
decreased significantly.
Randomized, double-blind,
sham, lesion, controlled trial
Study duration: 6 months
RF, n = 20
Sample sizes: PRF, n = 20;
Randomized, prospective,
double-blind study
Table 1. Pulsed Radiofrequency versus Conventional (Thermal) Radiofrequency
Both RF and PRF are effective and safe in the treatment of facet joint-mediated
pain, but the effects of PRF
are not as durable.
In contrast to observational
evidence, PRF is ineffective
for the treatment of trigeminal neuralgia.
Pulsed Radiofrequency Current in the Treatment of Pain
et al.16
Kroll et al.15
Sample sizes: PRF, n = 37;
PRF + RF, n = 39
Randomized, prospective pilot
Study duration: 3 months
PRF, n = 13
Sample sizes: RF, n = 13;
Randomized, double-blinded
There was no significant difference
in the percentage of successful
responses or in the reduction in VAS
scores between the 2 groups. For
both groups there was a large drop
off in the analgesic effect of the RF
treatment between months 2 and 4.
Most patients in both groups returned
to their baseline pain intensity after 8
In the PRF group, a comparison of
relative change over time in VAS and
OSW scores was not significant; in the
RF group, however, the VAS and CRF
scores improved significantly over time.
Both groups showed relative improvement in VAS and OSW scores, with no
significant difference noted.
There is a lack of additional
benefit when adding RF
to PRF; the electrical field
effect, and not the heating effect, of either treatment modality may be the
important factor influencing neuronal activity and
modulating pain. Overall, a
70% positive response rate
to PRF at about 2 months
after the procedure echoes
that documented by Van
Zundert in 2003.65
Both RF and PRF are effective and safe in the treatment of facet joint-mediated
pain. There is no significant
difference between RF and
PRF therapy in long-term
outcome; over time, however,
a greater improvement was
noted with RF.
Table 1. Pulsed Radiofrequency versus Conventional (Thermal) Radiofrequency, continued
Hata et al
Critical Reviews™ in Physical and Rehabilitation Medicine
Pulsed Radiofrequency Current in the Treatment of Pain
The mechanisms of action of PRF are likely diverse and may include structural cellular damage26; neuronal activation27–29; alternations in gene expression30 (activation
of early responsive genes may lead to changes in gene expression later because the
activated genes are transcription factors, so changes in gene expression may be long
term, but not limited to the early stage); the global reduction of evoked synaptic
activity leading to a decrease in the transmission of pain impulses through C and
Aδ nerve fibers via long-term depression29,31,32; and the alteration of synaptic field
strength and long-term potentiation.33 All of these could potentially decrease the
transmission of pain impulses. In the prevailing theory, the PRF electrical current
reversibly disrupts impulse transmission in small unmyelinated C pain fibers without neuroablation or thermal destruction, while sparing larger nerve fibers that are
protected by their myelin sheath.24,34 Proposed mechanisms of action are reviewed
in Fig. 1; these are based on basic science and animal study data and have not been
validated clinically.
A. Structural and Ultrastructural Cellular Changes
Cellular dysfunction may occur secondary to high RF electromagnetic fields24,35
and short PRF heat bursts.27,35 Cosman and Cosman35 have demonstrated that
the electric fields generated in PRF may be capable of modifying neuronal membranes. Neurobiological studies demonstrate early28 and late29 changes in cellular
activity, which are independent of temperature, that occur in the rat dorsal horn
of the cervical dorsal root ganglion (DRG) after exposure to PRF current. Neuronal activation has been demonstrated in several experimental PRF studies.23–29
In addition, it has been suggested that structural cell damage can result from PRF
exposure to the DRG.26 Whether these findings are secondary to either high electromagnetic fields or to short heat bursts remains speculative. The relationship of
these findings to the interruption of nociceptive firing is also unknown. PRF has
been proposed to inhibit C fibers secondary to a phenomenon known as longterm depression.36
Podhajsky et al.37 exposed rat DRGs to PRF, conventional RF, and conductive
heat; animals were killed for histologic study at 2, 7, or 21 days after treatment. The
authors reported that PRF caused transient minor structural changes including endoneurial edema secondary to alterations in the function of the blood-nerve barrier,
fibroblast activation, and collagen deposition. These reported changes might prevent
the transmission of ions needed for propagation of a pain impulse. Data from similar
studies evaluating structural changes related to short-term PRF effects (1 hour) on
rat lumbar DRGs38 and long-term effects (21 days) on the sciatic nerve39 showed that
unmyelinated nerve fibers were normal in both studies. Myelinated axons, however,
showed severe nerve degeneration after conventional RF; however, only separation in
myelin configuration (myelinated axons) was noted after PRF in the sciatic nerve,39
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Hata et al
FIGURE 1. Summary of the available literature about the potential mechanisms of action of pulsed radiofrequency (PRF). Effects of the PRF electrical current are placed
into 1 of 2 categories: structural change effects or genetic change effects. The relationship between structural changes (including membrane modification), genetic changes,
and inhibition of nociceptive firing is not fully known. ATP, adenosine triphosphate; DRG,
dorsal root ganglion.
and interrupted myelin coverage was noted after PRF in the DRG.38 Together, these
findings support that the changes induced by PRF seem reversible and do not rely on
thermal injury. In addition, larger myelinated fibers are selectively preserved in PRF,
whereas neuroablation occurs to these same fibers in conventional RF.
Erdine et al.40 analyzed ultrastructural changes after PRF and showed that
PRF exposure results in relatively selective small (C and Aδ) fiber injury with
changes in the morphology of mitochondria, including membrane changes, and
disruption and disorganization of microfilaments within the axons. The authors
also note that microscopic changes in the axon membrane, such as changes in
ion channels or pumps, may be present but may not be evident during evaluation
using electron microscopy. The degree and selectivity of ultrastructural damage
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Pulsed Radiofrequency Current in the Treatment of Pain
seems to relate to the penetrance of the PRF electric field. This concept is where
PRF electrical and current fields penetrate the axonal cell membranes of the C
and Aδ fibers, causing greater disruption to inner structures. Inner electric field
calculations for each fiber type correspond to the degree and selectivity of the
ultrastructural damage. Although the authors conclude that ìthe relationship of
ultrastructural damage to antinociceptive effects of PRF remains to be clarified,
î they suggest that damage to mitochondria, via the fragility of their membrane,
causes an interruption in the essential adenosine triphosphate–mediated cellular
functions and in cellular metabolism, impeding the generation of pain signals.
The damage to microtubules and microfilaments may similarly impede the transmission of pain impulses.40
B. Alterations in Gene Expression
Various cell culture studies have noted changes in dorsal horn activity and increased cellular stress in small- and medium-caliber neurons in response to PRF
at or near the DRG.27–29,38 The application of PRF on cell cultures also induces
immediate early gene expression that is not mediated by heat.30 In vivo studies
comparing RF and PRF demonstrate an increase in c-fos immunoreactive neurons in the superficial laminae of the dorsal horn 3 hours after application of
PRF, but not conventional RF, to the DRG, suggesting the activation of painprocessing neurons is not mediated by heat.28 Van Zundert et al.29 reported that
an increase in c-fos immunoreactive cells in the dorsal horn was noted 7 days after
both continuous RF and PRF were applied to the cervical dorsal root, representing late neuronal activation. In addition, Hamann et al.27 revealed an upregulation of activating transcription factor 3 (ATF3) in DRG neuronal cell bodies but
not in other nerve sections, such as the sciatic nerve, that were subjected to PRF.
ATF3 is a recognized marker of cellular stress and neuropathy; its upregulation
may indicate that PRF likely has a biological effect that is independent of thermal damage.41 Expression of the c-fos gene can lead to the formation of a second
RNA messenger, preprodinorphin, which increases the production of endorphins
that may modulate analgesia.42 Expression of c-fos may also act on inhibitory and
excitatory neurons and the dorsal horn of the medulla.43 Neurons expressing cfos may be inhibitory interneurons that reduce nociception.41 Overall, changes in
gene expression induced by PRF may reflect changes in the properties of dorsal
horn neurons in the direction of nociception reduction.
To the best of our knowledge, there are only 4 animal studies that reported changes
of behavioral sensitivity in animal pain models before and after PRF. Ozsoylar et
al.44 examined the effect of percutaneous PRF in a rat model of unilateral L5 and
L6 spinal nerve ligation. PRF was performed peripherally via an active needle placed
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Hata et al
percutaneously into the plantar side of the affected paw. A Von Frey filament and dynamic plantar aesthesiometer were used to test changes in paw withdrawal thresholds
to mechanical tactile stimulation after 2 to 6 minutes of PRF or sham PRF for up to
14 days. The authors found that PRF for 2 minutes resulted in a significant decrease in
allodynia in the injury group compared with sham treatment. Increasing the duration
of PRF to 6 minutes did not significantly improve allodynia. This study40 is interesting because it is one of the few that examine symptomatic improvement in an animal
model. In clinical practice, however, PRF usually is applied adjacent to the DRG or
to the medial branches of the dorsal rami (for the treatment of facetogenic pain). A
minority of human clinical studies use percutaneous PRF applied subcutaneously in
the periphery; one example does include occipital neuralgia.5 The clinical relevance of
findings from this study is limited because the experimental design does not mimic the
conventional application of PRF in clinical practice.
Hagiwara et al.45 studied the analgesic effects of PRF in an inflammatory pain
model induced by injection of Freund’s complete adjuvant into rat right hind paws.
Thermal hyperalgesia was measured using paw withdrawal latency to infrared radiant
heat before adjuvant injection and at days 1, 2, and 3 after injection. The rats were
divided into 4 groups: sham treatment, PRF 42°C, PRF 37°C, and RF at 42°C. PRF
(at 37 or 42°C), continuous RF (at 42°C), or sham treatment was administered to
the sciatic nerve after hyperalgesia induced by Freund’s complete adjuvant occurred­.
Findings from the study revealed a significant decrease in hyperalgesia in the 42°C
PRF group compared with the sham and to the continuous RF groups for the 3-day
experimental duration. The level of analgesia noted in the 42°C PRF group was significantly higher than the RF-mediated analgesia for all experimental time points. In
addition, yohimbine (an α-2-adrenoceptor antagonist), methysergide (a nonselective
serotonin receptor antagonist), and a selective 5-HT3 serotonin receptor antagonist,
administered intrathecally into the 42°C PRF group 48 hours after induction of hyperalgesia, all reduced the analgesic effect of PRF. The authors concluded that the
analgesic effect of PRF involves enhancement of descending inhibitory pathways,
specifically those involving the noradrenergic and serotonergic systems.45 The findings from this study are interesting and support PRF-induced analgesia in an animal
model. This study also at least partially elucidates the underlying mechanism of PRFinduced antinociception. The observation time, however, was short (3 days), and
long-term changes in behavioral hypersensitivity, therefore, may have been missed.
Aksu et al.46 studied the effects of PRF applied to the L5 and L6 dorsal roots
in a rabbit model of neuropathic pain. PRF was applied to rabbits that underwent
tight ligation of the sciatic nerve with silk sutures. Control animals included those
that received ligation of the sciatic nerve without PRF as well as a true sham control
(uninjured reference group). PRF was applied to the dorsal roots at 42°C for 8
minutes. Behavioral outcomes include testing to both thermal stimuli, via the hot
plate test, and mechanical stimuli, via hind paw withdraw threshold to a modified
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Pulsed Radiofrequency Current in the Treatment of Pain
rigid needle device, for 4 weeks after PRF. In rabbits that did not receive PRF,
mechanical and thermal hyperalgesia were persistent for 4 weeks. In rabbits that
received PRF, both mechanical and thermal hyperalgesia decreased 2 weeks after
PRF, when measured by the hot plate test for thermal hyperalgesia, and at 3 weeks
after PRF, when measured by mechanical stimulation testing. Antinociception was
so profound that basal values were achieved within 4 weeks after PRF treatment.46
These findings suggest that PRF applied adjacent to the dorsal root may alleviate neuropathic pain. The authors did not mention the role of the DRG in PRFinduced antinociception. Given the proximity of the dorsal roots to the DRG and
given findings by Hamann et al.27 that demonstrated upregulation of the transcription factor ATF3 in DRG cells after PRF, we speculate that modulation of the
DRG may play a role in the findings of Aksu et al.
Perret et al.47 studied the effects of PRF applied to the L5 DRG in a rat model of
neuropathic pain via spinal nerve ligation. Injured rats developed tactile allodynia;
one group received sham treatment while the other group received PRF treatment
of the L5 DRG. Behavioral testing after treatment revealed that PRF-treated animals exhibited better recovery than sham-treated animals on 10 of the 14 treatment
days after PRF. This reversal of allodynia indicates that PRF acts via modulation
of the DRG to speed recovery from pain induced by nerve injury and confirms the
role of the DRG in PRF antinociception.
In summary, basic science and animal studies provide some information regarding how PRF interacts with tissues and hint at how PRF may modulate pain. The
potential mechanisms of action may be numerous and are not fully delineated.
There are few animal studies that are available to confirm pain modulation behaviorally. These few studies demonstrate an improvement in tactile allodynia (and one
in thermal hyperalgesia) after the application of PRF. The proposed mechanisms of
action that induce this analgesia remain unclear. The determinants of effectiveness
also remain unclear. For example, conventional RF and PRF result in very different
levels of nerve injury; whether the degree of nerve injury plays a role in effectiveness
is yet to be determined. Future animal research should consider the tissue penetration effects of PRF and should alter technical aspects of PRF, including voltage,
cycle number, pulse duration, and electrode distance parameters. Basic science and
animal studies need to elucidate definite PRF mechanisms of action and determinants of effectiveness. Additional animal studies are needed to confirm true pain
modulation. In addition, animal studies ultimately will be clinicians’ resource for
patient selection, administration parameters, and timing of PRF treatment. The
study of PRF in a greater number of animal models also will help clinicians select
patients appropriately. Models that better target chronic pain, central pain (perhaps
spinal cord injury), radicular pain (perhaps chronic compression of the DRG), inflammatory pain, postoperative pain, Complex Regional Pain Syndrome (CRPS),
and perhaps visceral pain ought to be included.
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A. Facet-Mediated Pain
Although both traditional RF and PRF of the medial branches are believed to be
low-risk treatments, there has been a reported case of irreversible lower limb pain
attributed to thermal injury of the spinal nerve root during thermal (traditional)
RF of the lumbar medial branch nerves.48 PRF is likely safer than traditional RF
given that there is no neuroablation.25 A review of the literature reveals that traditional RF of the medial branches for the treatment of facetogenic pain is well
validated. The benchmark for thermal (traditional) lumbar medial branch RF is at
least 80% relief of pain for 1 year.25,50 The benchmark for the cervical spine is complete (100%) pain relief for 1 year.25,51–53 No studies report complications from PRF
in the treatment of facet joint pain.
Tekin et al.14 published the only randomized controlled trial for the treatment
of facetogenic pain; it compares RF and PRF in the treatment of chronic lumbar
facet joint pain. 60 patients were included in the study, and all had a single positive
response to diagnostic medial branch block. Patients were randomized into traditional RF, PRF, and control RF groups. Anesthetic injectate at the medial branch
was applied in all groups except PRF. The Visual Analog Scale (VAS) and Oswetry
Disability Index were evaluated before the procedure and at 6 hours, 6 months,
and 1 year after the procedure. All groups showed a decrease in VAS and Oswetry
Disability Index scores after the procedure.14 However, only the conventional RF
group maintained a decreased VAS score for the duration of the trial. At 1-year
follow-up, the number of patients not using analgesic medications and patient satisfaction were higher in both RF treatment groups than in the control group. The
highest scores were found in the traditional RF group. Limitations were noted by
the authors and include the potential risk of a false-positive single diagnostic block.
In addition, although there was long-term data, there was no data between 6 hours
and 6 months after the procedure. In light of the fact that retrospective studies
suggest an average effectiveness of radiofrequency at 4 months,54 this may indicate
a flaw in study design. The authors concluded that both RF and PRF are effective
and safe in the treatment of facet joint–mediated pain but that the effects of PRF
are not as durable.14
A randomized, noncontrolled, double-blinded study by Kroll et al.15 suggests
similar findings. Kroll et al. performed 2 separate diagnostic lumbar medial branch
blocks to confirm facetogenic pain in 50 patients. Patients then received either
conventional RF or PRF as a treatment modality; only 26 completed a 3-month
follow-up. Outcome measures included the VAS and Oswetry Low Back Pain and
Disability Questionnaire. The results suggest less ìsustained reliefî from PRF versus
RF. The study had major limitations, including a high dropout rate, small sample
size, lack of follow-up beyond 3 months, and lack of a control group. Although outcomes were similar in the RF and PRF groups, scores for both outcome measures
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Pulsed Radiofrequency Current in the Treatment of Pain
before the procedure were significantly lower in the PRF group and may have limited the amount of change observed. The authors concluded there was no significant difference between conventional RF and PRF therapy in long-term outcome
in the treatment of lumbar facet syndrome. Over time, however, a greater improvement was noted within the conventional RF group.15 The use of ìlong termî may be
misleading because the benchmark during conventional lumbar RF of the medial
branches is pain relief sustained for 12 months.25
A prospective noncontrolled trial by Liliang et al.55 studied PRF for the treatment of whiplash related cervical zygapophyseal joint pain. Fourteen patients
had a positive response (more than 80% pain relief) to double diagnostic medial
branch blocks. VAS and a medication use scale were assessed before treatment
and at 1, 6, and 12 months after treatment. Results showed significant pain reduction (more than 60% pain relief) in 85%, 78%, and 64% of patients at 1, 6, and
12 months, respectively. Medication requirements were reduced in 92%, 85%, and
71% of patients at 1, 6, and 12 months, respectively. The authors concluded that
PRF of the cervical medial branches is a potential treatment for patients with
chronic whiplash-related cervical zygapophyseal joint pain that has failed other
conservative treatments. The main study limitations were the small sample size
and lack of a control group.
Retrospective studies include PRF in the treatment of cervical and lumbar facet
joint pain. In one study,54 114 patients had a positive response to a single diagnostic block of the cervical or lumbar medial branches and underwent PRF; 58% of
patients had a successful response (with more than 50% pain reduction for up to
4 months). Limitations include the lack of a control group and the use of single
diagnostic blocks. In another study,56 the Numeric Rating Scale (NRS) pain scores
of 48 patients were assessed at baseline and at 1 and 4 months after PRF treatment
of the lumbar medial branches. Nineteen of the 48 patients had previous back surgery and were placed in a separate group. After a successful single medial branch
blockade, patients underwent PRF treatment. About 70% of the patients in the
nonoperated patient subset had successful treatment, which was defined as more
than 60% reduction in pain. In contrast, only 26% of previously operated patients
had a successful treatment outcome. Limitations include the study design and small
sample size, which did not permit comparison with traditional RF.
In summary, the use of PRF for facet joint pain seems to be a safe treatment. However, the magnitude and duration of effect seem to be less than that
of conventional RF. To eliminate nonspecific treatment, control groups are critical in study design. Future randomized controlled studies should pay particular
attention to include both short-term (less than 6 months) and long-term (6–12
months) follow-up intervals to establish the true efficacy of PRF in treating facet
joint–mediated pain. Despite the aforementioned studies, there remains a lack of
level 1 or 2 evidence showing efficacy of PRF for facet-medicated pain. There is,
however, existence of level 1 and 2 evidence for conventional RF for treatment of
facet-mediated pain.
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B. Radicular Pain
The DRG-directed application of RF current has been practiced for more than 30
years. The presumed advantages to DRG-directed current include the following:
the DRG is likely the major source of radicular pain; creation of a more permanent
lesion/modulation due to targeting the neuronal cell bodies; creation of a more
complete lesion/modulation due to targeting the anterior spinal roots; and reduction in pain after RF by preventing DRG hyperactivity.20
For the treatment of radicular pain, Uematsu et al.19 first applied RF current
to the sensory spinal nerve roots. Although later publications recommended DRGdirected lesioning,57–60 there is some evidence that sustained pain from spinal nerve
root compression or mechanical stimulation may occur when the nerve root has
been injured or inflamed previously.61,62 A literature review, therefore, reveals both
DRG-directed and spinal nerve root–directed approaches. The techniques involved
in both cervical and lumbar DRG-directed RF application are reviewed by Malik
and Benzon.20 A unique trans-facet joint approach to successful PRF of the L5
DRG in a patient with lumbar radiculopathy secondary to foraminal stenosis also
has been described.63
1. Cervical Radicular Pain
In a 2008 review by Van Boxem et al.,2 one randomized controlled trial64 and one
clinical audit65 are analyzed. In the retrospective audit published by Van Zundert et
al.65 in 2003, long-lasting pain relief was reported in 72% (of 18 patients) at 2 months,
in 56% at 3–11 months’ follow-up, and in 33% for more than 1 year, all after PRF application to the cervical DRG for the treatment of cervical radicular pain. The results
of this initial audit prompted the first randomized controlled trial using PRF for the
treatment of chronic cervical radicular pain. Twenty-three patients with cervical radicular pain confirmed by diagnostic block were randomized to receive either sham or
PRF. Patients were followed for 3 to 6 months. Outcomes included VAS pain scores,
Global Perceived Effect (GPE) scores, use of analgesic medications, the 36-item Short
Form and Euroqol scales for quality of life. At the 3-month follow-up only, statistically significant (P = 0.03) differences between the treatment and sham groups were
noted for the GPE scores, where at least a 50% improvement was defined as success,
and for VAS scores (P = 0.02), where a 20-point reduction (of 100) in pain intensity
measured success. A decrease in the use of pain medication also was noted. Quality
of life measurements trended toward better results in the PRF group after both 3 and
6 months, but statistical significance was not achieved.64 No study complications were
noted. The authors concluded that PRF may provide analgesia for select patients
with cervical radicular pain. Study flaws included differences in sham versus treatment group baseline demographic characteristics and the small sample size.
In a prospective uncontrolled trial, Pevzner et al.66 performed PRF for patients
with cervical and lumbar radicular pain. At the 3-month follow-up, 2 patients had
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Pulsed Radiofrequency Current in the Treatment of Pain
ìexcellent, î 12 patients had ìgood,î and 9 patients had ìfairî pain relief, while 5
patients reported no analgesia.
A study involving patients with cervical and lumbar radicular pain was published by Chao et al.41 in 2008. In this retrospective study, 49 patients with cervical
radicular pain involving the C3 through C7 roots were included among the 154
patients in the study who underwent PRF. The cervical DRG was the target of
the PRF current. In this group, the authors noted the following results of cervical
radicular pain: 53.06% (26 of 49 patients) had >50% improvement in VAS during
the first week of follow-up, 55.10% (27 of 49 patients) had >50% improvement in
VAS at the 3-month follow-up, and 57.14% (4 of 7 patients) had >50% improvement in VAS at the 1-year follow-up. Results for the treatment of lumbar radicular
pain were reported as follows: 50.86% (59 of 116 patients) had > 50% improvement
in VAS during the first week of follow-up, 44.83% (52 of 116 patients) had >50%
improvement in VAS at the 3-month follow-up, and 23.26% (10 of 43 patients) had
>50% improvement in VAS at the 1-year follow-up. 41
2. Lumbar Radicular Pain
In 1998, Sluijter et al.24 treated 15 patients with lumbar radicular pain via PRF at
the appropriate DRG. Success was defined as a >2 point reduction in VAS score;
this occurred in 53% (8 patients) at the 6-month follow-up and in 40% (6 patients) at
the 12-month follow-up. In 1999, Munglani67 published 3 case reports regarding the
application of PRF for lumbar radicular pain. In all 3 cases, analgesia lasting 1 to 7
months was reported. In 2005, Teixeira et al.68 retrospectively reviewed 13 patients
with lumbar radicular pain who underwent PRF. At least a 5-point reduction in
NRS pain scores was noted in 92% of patients at the 1-year follow-up. In addition,
the authors note that in 9 patients who presented with dermatomal or myotomal
deficits on physical examination, all 9 patients had resolution of radiculopathy after
the PRF treatment.
In 2007, Abejon et al.69 published a retrospective analysis of 54 patients who
received PRF for lumbar radicular pain. All patients had a positive response to a diagnostic confirmatory transforaminal-type local anesthetic nerve block. Although
all patients had a predominance of radicular pain, the patients were classified by
pain etiology, including disc herniation (n = 29), spinal stenosis (n = 12), and failed
back surgery syndrome (n = 13). NRS and GPE were outcome measurements at
baseline and at 30, 60, 90, and 180 days after treatment, as was reduction in the
use of analgesic medications. A reduction in medication requirements as well as
treatment success, which was defined as a GPE score of greater than 5 at the 60-day
follow-up assessment or a decrease of 2 points in the NRS pain score, was noted for
patients with herniated disc disease (number needed to treat = 1.38 patients) and
spinal stenosis (number needed to treat= 1.49 patients) but not for patients with
failed back surgery syndrome (number needed to treat= 6.5 patients).69 The small
sample size and lack of uniformity in pain etiology are concerns.
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Hata et al
A prospective evaluation of PRF for the treatment of lumbar radicular pain
was published in 2008. In this study, 76 patients with lumbar radicular pain and
confirmed responses to diagnostic/therapeutic blocks were randomized to PRF of
the DRG (n = 37) or PRF of the DRG followed by conventional RF of the same (n
= 39).16 In the case of S1 radicular pain, the segmental nerve was targeted because
of inaccessibility of the DRG. In this study, the addition of the thermal lesion via
conventional RF did not show a statistically significant added benefit. Success of
PRF treatment was defined by at least a 2-point reduction (and/or 30% improvement) in VAS pain scores for at least 8 weeks. The average duration of analgesia
was 3.18 (±2.81) months for the PRF group and 4.39 (±3.5) months for the PRF
plus conventional RF treatment group. By the eighth month, nearly all patients’
pain had returned to baseline. The authors discuss the lack of additional benefit
when adding RF to PRF. They surmise that the electrical field effect, and not the
heating effect, of either treatment modality may be the important factor influencing
neuronal activity and modulating pain.16
In summary, evidence suggests that PRF for the treatment of both cervical and
lumbar radicular pain is beneficial. No complications are noted and decent response
rates (50%–70%) are noted until about 2 to 4 months after treatment.16,41,65 In the treatment of lumbar radicular pain, the lack of additional benefit noted when RF is combined with PRF in the study by Simopoulos et al.16 suggests that the electrical field (and
not heating) effect is the modulating factor; this correlates with basic science data that
highlight that there are structural/ultrastructural changes and gene expression changes,
including ATF3 upregulation, that are secondary to nonthermal PRF application.
C. Sacroiliac Joint Pain
A literature search reveals a single prospective study where PRF is applied to
the sacroiliac joint. Vallejo et al.3 report on the application of PRF in 22 patients who failed to respond to traditional conservative treatments. The study
enrolled 126 patients with presumptive sacroiliac joint pain based on history,
radiology, and physical examination findings. PRF (45 volts for 120 seconds)
was applied to the medial branch of L4, posterior primary rami of L5, and
lateral branches of S1 and S2. Two lesions were made at each location; at each
target, sensory and motor stimulation confirmed correct probe placement before application of PRF. Sixteen patients (72.7%) experienced good (>50% reduction in VAS) or excellent (>80% reduction in VAS) pain relief after PRF. The
mean relief duration in the 16 responders was 20.0 ± 5.7 weeks. VAS pain score
and the Physical Well Being and Functional Well Being subcomponents of the
Functional Assessment of Chronic Illness Therapy Quality of Life assessment
achieved statistical significance at 6 months’ follow-up. No study complications
were reported. In the study, 70.6% of patients presented with additional concomitant pain complaints. The multiple sources of pain may be an explanation
for treatment failure in 6 patients; inadequate PRF is also a possibility. Overall,
Critical Reviews™ in Physical and Rehabilitation Medicine
Pulsed Radiofrequency Current in the Treatment of Pain
a high percentage of patients (>70%) treated with PRF to the sacroiliac joint, all
of whom had otherwise intractable pain, reported sustained good or excellent
pain relief.3 As is the case for other applications of PRF, high quality, blinded,
randomized, controlled trials still are required to clarify the benefit of PRF
technology further.
D. Trigeminal and Other Neuralgias
Orlandini4 provided a technical description of and insight into patient selection. Van
Zundert et al.70 provided a small case series of 5 patients with idiopathic trigeminal
neuralgia that were treated with PRF. The mean follow up was 19.2 months, and
the study reported ìexcellent long term effectî in 3 patients, ìpartial effectî in one
patient, and ìshort term effectî in one patient. Erdine et al.13 provided a randomized,
double-blinded, prospective, head-to-head examination of PRF versus conventional RF application to the Gasserian ganglion. The study was performed on 40 patients with a diagnosis of idiopathic trigeminal neuralgia. In the conventional RF
group, mean VAS scores at 0, 3, and 6 months were 1, 0.5, and 0.5, respectively (P
< 0.001). The PRF group had a mean VAS score of 8 at both 0 and 3 months, and
only 2 of the patients in the PRF group derived significant pain relief for a period
of 3 months. For all other patients in the PRF group who still had intractable pain
at 3 months, conventional RF was performed for palliation. The mean VAS score
for the crossover group was 1 (0–10 scale) when evaluated 3 months after treatment
with conventional RF. In this PRF versus RF comparison study, traditional RF far
outperformed PRF.
1. Chronic Pain After Thoracotomy
Chronic thoracic pain after surgery has a reported incidence of 25%–60%71 and rarely
improves over time.72 A review of the literature yields a single retrospective nonrandomized trial reported by Cohen et al.6 Medical management versus PRF of the intercostal nerves versus PRF of the DRG was studied in 49 patients. Successful treatment
was defined as ≥50% pain reduction on a VAS and affirmative answers to 2 questions
evaluating patient satisfaction and functional improvement. At 6 weeks, results did
not achieve statistical significance. However, statistical significance at 6 months was
reached when the group with PRF treatment of the DRG was compared with the
group with PRF treatment of the intercostal nerves (P = 0.01) and approached significance when compared with medical management (P = 0.06). There are several
important limitations in this study, which include the retrospective design, lack of
randomization, and lack of standardization of treatment protocols. In addition, recent data show that only approximately 50% of chronic pain after thoracotomy is
of neuropathic origin.73 No validated method was used in this study to determine
whether patients’ pain was neuropathic. Finally, unlike the 2 PRF groups, the medical
management group did not receive homogeneous treatment.
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Hata et al
2. Other Neuropathic Pain
A study by Shabat et al.74 involved 28 patients with chronic spinal neuropathic pain
who underwent PRF treatment of the associated DRG. A large majority of patients
(82%) reported analgesia at the 3-month follow-up and again (68%) at the 1-year
follow-up. The nature and etiology of the spinal neuropathic pain was not described
and the study is confounded by concurrent treatments. Rhame et al.7 describes a
transvaginal approach for application of PRF to the pudendal nerve. After the procedure, the patient reported improved tolerance when sitting, was weaned from her
multianalgesic therapy, and returned to work 5 months after the procedure. Followup at 1.5 years reports the patient has continued ìgood sitting tolerance. î Navani et
al.5 described the application of PRF current to the greater occipital nerve in a single
patient. PRF resulted in 4 months of 60%–70% analgesia. The patient had subsequent reapplication of PRF, producing similar analgesia for 5 months. A single case
report8 of PRF applied directly to the ilioinguinal nerve describes a patient who
presented with a 3-year history of persistent left groin pain (rated 10 of 10) after a
traumatic injury. After failing conservative therapy, the patient underwent 4 cycles
of percutaneous PRF of the left ilioinguinal nerve. At 3 months after the procedure
the patient’s pain was rated 3 of 10 on a VAS both at rest and during vigorous exercise. Rozen and Ahn9 published a case series of 5 patients in whom PRF was applied
to the DRG at the T12, L1, and L2 spinal levels for treatment of ilioinguinal neuralgia after inguinal herniorrhaphy. Four of 5 patients reported pain relief lasting for
4 to 9 months. One case report10 of an 84-year-old woman with glossopharyngeal
neuralgia following right tonsillectomy was found in the literature. A diagnostic
glossopharyngeal nerve block resulted in complete but transient resolution of her
pain. She reported 8.5 months of complete pain relief after PRF. Following this,
the patient had return of pain that was refractory to multiple systemic analgesics.
She underwent 2 subsequent PRF treatments that provided complete pain relief for
6 and 8 months, respectively. Haider et al.75 describe a single case report of the use
of PRF for the treatment of an individual with carpal tunnel syndrome who had
recurrent symptoms despite aggressive medical and surgical management, including
multiple carpal tunnel release surgeries. After a diagnostic median nerve block provided complete pain relief, the patient underwent 3 applications of PRF: one ventral to the target nerve, one medial to the target, and one dorsal to the target. The
patient endorsed 70% analgesia after the procedure that was sustained throughout
the 12-week follow-up period. Ramanavarapu and Simopoulos76 presented a small
case series of 2 patients; both had stump pain that was considered to be due to
formation of a neuroma at the sites of sciatic and saphenous nerve ligations. The
patients initially underwent diagnostic injection of the neuroma, with 100% resolution of symptoms. The L4, L5, S1, and S2 DRGs were postulated as conduits for
continued transmission of a pain signal from the neuroma. Both patients had positive responses (>50% relief) to transforaminal blockade and proceeded to undergo
PRF, after concordant sensory stimulation, to the L4 and L5 DRGs. One patient
Critical Reviews™ in Physical and Rehabilitation Medicine
Pulsed Radiofrequency Current in the Treatment of Pain
had 90% pain relief for 2 months; at the 6-month evaluation she reported 50% pain
relief. The other patient had a 70% reduction in VAS score that lasted for 6 months.
3. Pulsed Radiofrequency of the Sphenopalatine Ganglion for Treatment
of Headache
Shah and Racz77 presented a patient who suffered a traumatic brain injury and had
been experiencing intense episodic headaches daily for a period of 7 years. The
patient had been refractory to a number of medications but had complete alleviation of his pain with a bilateral intranasal sphenopalatine block for 2 months. The
patient subsequently underwent 3 cycles of PRF, after concordant sensory stimulation, to the right sphenopalatine ganglion. This initial treatment decreased the frequency of his headaches to one per month for 3 months; then symptoms gradually
returned. The patient subsequently underwent bilateral PRF of the sphenopalatine
ganglion and continued to be free of headache for 19 months.
E. Complex Regional Pain Syndrome
There is a single case report describing a 55-year-old woman with bilateral CRPS after spinal cord injury. The patient reported marked analgesia following a diagnostic
lumbar sympathetic block, and subsequent PRF of the lumbar sympathetic ganglia
was performed at the L2, L3, and L4 vertebral levels. Results included a decrease in
VAS pain scores from a score of 95 mm before the procedure to 25 mm on the 10th
day after the procedure. Vasomotor and sudomotor changes disappeared within 3
days of the PRF. The results were stable over the 4-month follow-up period.78
F. Discogenic Pain
In 2006, Teixeira and Sluijter79 published a preliminary report of the application of
PRF to the intervertebral disc in 8 patients with axial low back pain of discogenic origin
refractory to conservative management. All patients had facetogenic pain excluded by
diagnostic medial branch blocks and had concordant pain reported on diagnostic discography. For the procedure, 20 minutes of high-voltage PRF was performed at the disc
center. All patients had a decrease in pain score of at least 4 points on the NRS in the
first 3 months of follow-up. Long-term follow-up of 12.8 months showed 4 of 5 patients
becoming pain-free and one patient retaining an NRS score of 2.
G. Myofascial Pain
Tamimi et al.11 provided a small retrospective review describing their experience with the
percutaneous application of PRF technology to patients with myofascial pain. Eight of
the 9 patients treated had between a 75% and 100% reduction in pain after PRF treatment. Six of the 9 patients experienced 6 months to 1 year of significant pain relief.
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Hata et al
H. Joint Pain
Sluijter et al.12 presented a series of case reports that evaluated the use of PRF in the
treatment of chronic arthrogenic joint pain of the knee, radiocarpal joint, shoulder,
and atlantoaxial joints. PRF was performed in patients that failed both conservative and other invasive treatment. Pain relief was noted in each case, with a duration
of effect lasting 8–12 months.
1. Shoulder Pain
PRF of the suprascapular nerve was first described in 2002.67 Rohof80 evaluated
PRF of the suprascapular nerve by performing a retrospective analysis of 37 study
participants with chronic shoulder pain. After treatment, an average reduction in
pain score of 4.5 points (of 10 points total) was noted. Shah and Racz81 published a
case report of a patient with adhesive capsulitis and osteoarthritis who underwent
4 PRF treatments to the suprascapular nerve over a 16-month period. The authors
concluded that PRF was easily reproducible, decreased pain intensity, and increased
function for an average of 12–18 weeks. In 2009, Liliang et al.82 performed PRF on
13 shoulders in 11 study participants who failed conservative treatments. Subjects
reported a significant decrease in shoulder pain and in disability index at 6 months.
In addition, 9 of 11 patients required less pain medication after PRF. Kane et al.83
evaluated the effects of PRF in 12 patients with painful arthropathy of the rotator
cuff in the context of significant medical comorbidities. Patients’ scores improved
in comparison to baseline scores on the VAS, Oxford Shoulder Score, and Constant
Shoulder score at both 3 and 6 months.
2. Hip Pain
In 2001, Kawaguchi et al.84 reported 14 cases of hip pain that were treated by conventional RF of the femoral nerve, obturator nerve, or both. Twelve cases had a
>50% reduction in pain for 1 to 11 months. Similar results were noted in an additional RF case report.85 Wu and Groner86 applied PRF to the femoral and obturator nerves to treat 2 cases of hip pain. They reported a significant decrease in pain
and increased patient function at 3 to 4 months.
I. Other Novel Applications of PRF
Other applications of PRF outside of the field of Pain Medicine have been explored. Seref et al.87 recently used PRF for the treatment of premature ejaculation.
His group postulated that by decreasing the sensitivity of the glans penis, ejaculation could be delayed. A statistically significant increased time to ejaculation as
well as significantly improved sexual satisfaction of patients and their partners was
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Pulsed Radiofrequency Current in the Treatment of Pain
PRF also has been found to have utility in the treatment of nonhealing wounds
based on the ability of low-energy PRF current to induce cell proliferation. Frykberg
et al.88 retrospectively described a small cohort of patients with nonhealing wounds
treated with PRF. Porreca and Giordano-Jablon89 described the use of PRF as an adjuvant to basic wound care on a tetraplegic patient with 3 long-standing stage III and
IV decubitus ulcers that were previously refractory to all other treatments; the patient
had complete resolution of 2 ulcers and a 95% reduction in the size of the third.
A single publication containing 4 cases details the novel application of PRF
transcutaneously through conventional transcutaneous electrical nerve stimulation
electrodes. Two cases reported involved successful PRF treatment of axial low back
pain that followed previous spinal fusion surgery; a third case involved successful
PRF treatment of radial wrist and hand pain due to trauma and 21 surgeries. PRF
treatment of axial cervical spine pain after fusion was not successful.92
The data compiled here largely represent knowledge gained from retrospective and
uncontrolled trials (see Table 2 for a summary of the clinical data). We are reminded
that in the management of pain, evidence-based medicine is limited. Randomized
controlled trials may be difficult to execute, and other forms of knowledge, including basic science studies and other clinical trials, are valid sources of data and ought
not to be dismissed. Particularly for emerging treatments and when there is desperation to palliate pain, evidence-based medicine may provide little resources for the
pain medicine practitioner. Given the challenge of treating CRPS, for example, the
report of successful lumbar sympathetic ganglia-directed PRF,78 despite its limitation as a single observation, probably represents an exciting application of PRF
energy for most pain physicians. Nonetheless, observational evidence does not and
cannot replace evidence-based medicine. In addition, the limitations of observational evidence need to be weighed.
In the search for a modality that relieves pain, PRF seems to be safe, and clinical
studies demonstrate at least some efficacy. There are, however, significant arguments
against PRF. From a mechanistic point of view, PRF seems to primarily interrupt
signals in unmyelinated C fibers. This mechanism of action would potentially leave
Aδ fibers preserved to continue transmission of pain signals. Patients may have various levels of transmission of pain signals in C fibers versus Aδ fibers, and PRF as
a treatment modality may better suit patients with high C-fiber pain transmission.
The consequences and significance of c-fos expression (and other genetic changes
such as ATF3 upregulation) are not fully known (although genetic changes seem to
lead to reduced nociception). The relationship of ultrastructural damage to the antinociceptive effects of PRF also needs to be clarified. The importance of thermal
lesioning, as noted in traditional RF, or its absence, as noted in PRF, is unknown.
The relationship of the thermal lesion to analgesia is also yet to be determined. In
addition, as noted throughout this article, there are significant limitations to both
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Lumbar: 1
1 (6)
Facet pain
Trigeminal: 1 (22)
Occipital: 1 (23)
After thoractomy: 1 (24)
Spinal pain: 1 (25)
Pudendal: 1 (26)
Ilioinguinal: 2 (27,28)
Glossopharyngeal: 1 (29)
Sphenopalatine: 1 (30)
After amputation: 1 (31)
CRPS: 1 (32)
Carpal tunnel: 1 (33)
Questionable analgesia
compared with conventional
RF for trigeminal neuralgia;
approximately 3–6 months of
moderate analgesia is noted
across multiple case reports
and retrospective studies for
other neuralgias.
Lumbar: 6 (10–12,17–19)
Lumbar: 1 (8)
Sacroiliac: 1 (20)
Cervical: 2 (9,10)
Lumbar: 2 (4,5)
Lumbar: 1 (3)
Cervical: 1 (7)
Cervical: 1 (4)
Retrospective Studies/
Case Reports (n)
Cervical: 1 (2)
Studies (n)
joint pain
1 (17)
RCTs (n)
Table 2. Numbers and Types of PRF Studies by Pain Etiology
A high percentage of patients
responded with good to excellent analgesia.
Lumbar: Significant analgesia
for 2–4 months; resolution of
neurologic deficit reported;
~70% response rate noted.
Cervical: PRF may provide
analgesia for select patients;
~70% response rate.
PRF may provide less sustained relief than RF; positive
results are noted.
Hata et al
Critical Reviews™ in Physical and Rehabilitation Medicine
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Knee: 1 (36)
Joint pain
Hip: 1 (41)
Shoulder: 4 (37–40)
Atlantoaxial joint: 1 (36)
1 (36)
Myofascial: 1 (35)
Studies (n)
Lumbar: 1 (34)
RCTs (n)
Shoulder: moderate duration
(>6 months) of analgesia is
demonstrated; long-term relief
of other arthrogenic pain in
several case reports.
A single study shows impressive analgesia (75–100%) for
6–12 months.
A single study shows
moderate analgesia.
Retrospective Studies/
Case Reports (n)
Table 2. Numbers and Types of PRF Studies by Pain Etiology, continued
Pulsed Radiofrequency Current in the Treatment of Pain
Hata et al
animal behavioral and clinical study data. The primary limitation is, of course, the
overall paucity of data. In the clinical arena, PRF remains a novel treatment because of the lack of a significant body of data from randomized controlled trials.
Our understanding of PRF undoubtedly has progressed in the past few years,
despite these limitations. Knowledge regarding the mechanisms of action of PRF
has advanced from a ìblack boxî concept to knowledge of definitive changes in
cellular structure and in genetic expression. The summative effect of these possibly
reduces nociception. PRF has been supported further by animal behavioral studies
that confirm improvement of both thermal hyperalgesia and mechanical allodynia,
which show that the analgesic effect of PRF involves enhancement of descending
noradrenergic and serotonergic inhibitory pathways. There is sparse accumulation
of clinical observational evidence, and some evidence from randomized controlled
trials shows that PRF provides some analgesia in humans. All of these data suggest
that PRF may hold promise as an analgesic modality to treat a variety of conditions.
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