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Any thoughts on this month's issue of Pain Medicine?
September/October 2006 - Vol. 7 Issue 5 Page 369-470
ISIS Position Paper on Pulsed RF
Nikolai Bogduk
(396-407)
Discussion
There are stark differences between thermal RF lesioning techniques and pulsed RF treatment. 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, histologically verifiable tissue lesion, and there is no dispute of this being the objective of the procedure. There is strong evidence of outcome, not only with respect to relief of pain but also in terms of restoration of function and even resolution of psychological distress. The procedure has been vindicated by placebo-controlled trials. The relief of pain from properly performed RF neurotomy is profound. The benchmark is total relief of pain or nearly so. The nominal duration of relief is 1 year. Although pain may recur in some patients as the peripheral nerve regenerates, relief can be successfully reinstated by repeating the neurotomy.
What is clearly evident from the literature is that pulsed RF does not produce a lesion. Therefore, pulsed RF cannot be represented as a procedure resulting in nerve destruction, neurotomy, 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.
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 placement of electrodes is not critical, this also renders pulsed RF a faster procedure than thermal RF. It would not be surprising, therefore, if some practitioners have adopted pulsed RF simply because it is a quicker, easier procedure.
Observer bias is probably another factor. Practitioners who adopt the procedure are likely to remember their successful cases, but forget the failures. Moreover, their impressions of the effectiveness 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 attenuation of effects over time. Under those conditions, a procedure with fair to reasonable short-term outcomes may look attractive. Only when longterm follow-up is conducted does the true effectiveness, or lack thereof, emerge.
Another factor that attracts practitioners to pulsed RF, especially those who have limited clinical experience or technical skill in percutaneous interventions, is the purported reduction or avoidance of side effects and complications associated with thermal RF, as the intent of pulsed RF is specifically 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 final attraction is financial. Pulsed RF becomes very attractive if it carries the same reimbursement 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 efficacy; pulsed RF does not.
• Using pulsed RF instead of thermal RF, where the latter is indicated, denies the patient the benefit 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 efficacy of thermal RF neurotomy unjustly impugns what should be an effective 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 of efficacy become available. Health care administrators must also understand that pulsed RF and thermal RF are different, nonequivalent procedures, having differing outcomes, and involving different degrees of medical risk, physician time and training.
Pulsed Radiofrequency Treatment: What Is the Evidence of Its
Effectiveness and Should It be Used in Clinical Practice?
Rollin M. Gallagher, MD, MPH, University of Pennsylvania, Philadelphia VA Medical Center, Pennsylvania, USA
(408-410)
Summary
Heretofore, critics understandably decried the lack of evidence for the clinical efficacy of PRF. Is this just another ballyhooed intervention that will drive costs higher without added benefit beyond existing treatments? PRF, if proven clinically effective, will surely find a place in our armamentarium because, compared with TRFN, PRF requires less precision in the placement of electrodes and is therefore faster to perform. Because tissue is not destroyed, it may be safer. Proponents tout its efficacy in controlling pain without actually destroying tissue, avoiding complications such as destruction of other sensory neurons and motor neurons. However, until recently, when Level 2&3 clinical evidence has been obtained, this enthusiasm is based upon testimonials of clinical experience rather than solid experimental evidence of the variety that convinces critics. The randomized, controlled clinical trial of Van Zundert et al., presented as IASP, begins the process of solidifying Level 3 and Level 4 evidence.
We owe it to our patients and the public to avoid stopping our use of this potentially valuable treatment as a "knee jerk" reaction to the lack of firm evidence. Rather, we should cautiously prescribe this promising intervention following clinical algorithms that are based upon the best clinical evidence available. However, it is critically important to avoid the mistake of creating a "carte blanche" environment for those practitioners who would abuse the privilege and opportunity presented by this new technology, besmirching our
credibility and ultimately impeding the opportunity to use this treatment to the benefit of the public. Ultimately, evidence, not reimbursement, should determine whether PRF finds a place in our clinical toolbox.
Pulsed Radiofrequency: Current Clinical and Biological Literature Available
Alex Cahana, Jan Van Zundert, Lucian Macrea, Maarten van Kleef, Menno Sluijter
(411-423)
Discussion
After an extensive literature search, we could detect 42 reports from 11 countries on the clinical use of percutaneous and transcutaneous PRF in different applications on a variety of (chronic) pain syndromes in 1,207 patients. Up till now in none of the listed reports, neurological side effects or complications with PRF were mentioned. Because this is a new technique, a substantial part of these results are reported in the abstract books of international scientific pain congresses. Their number is increasing yearly, and they are progressively published in peer-reviewed journals. This is a similar evolution to other techniques in medicine in general, and pain medicine in particular. Although there is an increasing focus in the literature for PRF, the question still remains: "What is its place in the pain management algorithm?"
In order to answer this question, it is important to understand the concept behind RF and PRF treatments. It is presumed that the mode of action of RF heat lesions is that by selectively heating nervous structures, denervation can impede nociceptive input. However, the observation that after RF treatment pain relief lasts longer than the sensory loss in the relevant dermatome, gave rise to the theory that heat is not the only mode of action and that other factors responsible for pain relief may be involved. Furthermore, the role of heat was further questioned after the results of Slappendel et al., who found no difference in patient outcome with RF treatment when an electrode tip temperature of 40°C was used compared with RF at 67°C. Thus, it was hypothesized that there must be another, perhaps additional, mechanism besides heat that alters pain signal transmission.
So PRF was conceived as a novel, potentially safer mode of administration of RF energy, whereby in 1 s, two bursts of 20 ms each of an alternating current are delivered. The oscillating frequency of the alternating current is 500,000 Hz. During one cycle, the "active phase" of 20 ms is followed by a "silent phase" of 480 ms to allow the generated heat to washout. The output is usually set at 45 V, but if the electrode tip temperature exceeds 42°C, the voltage is decreased.
In our review, we have shown that since the initial publication on PRF treatment for spinal pain in 1998, information from prospective and retrospective trials, as well as several case reports on the percutaneous use of PRF, is accumulating. Interestingly, the transcutaneous use of PRF, which is a different application, has been documented to provide good pain relief in different modes. The available information on PRF treatment does not allow pooling the data because of the differences in the reporting, but also because of the fact that the technical parameters such as voltage, impedance, time of application of the PRF current, and resulting electrode tip temperature are not always reported. There is an urgent need for a more standardized data collection and reporting.
In general, RF stimulation within frequencies between 300 Hz and 300 GHz create electric fields, which generate both current and heat on exposed biological substrates. It is clear that heat lesions of neural substrates above 45°C result in nonselective destruction of both myelinated and nonmyelinated nerve fibers. However, it has been shown that PRF and RF have differential neurobiological effects, aside from the heatinduced morphological changes; c-Fos activation, a marker for neuronal activity in the rat dorsal horn, has been reported to be expressed immediately (3 h) [84] and up to 7 days [85] after PRF treatment. The duration of Fos-like immunoreactivity exceeding the expected length of time for c-Fos expression caused by the acute effect of surgery and electrical stimulation of sensory nerves may be due to the inhibition of excitatory C-fiber responses as seen in long-term depression, according to an accompanying editorial [72]. Moreover, it has recently been reported that the biological effect of PRF was unlikely to be related to an overt thermal damage and appears to be selective in that it targets the group of neurons whose axons are the small-diameter C and Aδ nociceptive fibers.
We also found that PRF alters synaptic transmission. In vitro PRF stimuli of organotypic slices of the hippocampus induce transient decrease in excitatory postsynaptic potential with rapid and complete recovery, while in contrast, continuous RF creates long-lasting blockade of synaptic transmission even in temperatures <45°C. Both continuous and PRF treatments induce distancedependent tissue destruction under the stimulating needle, but the effect was more pronounced in the continuous group. Similarly, a morphological evaluation of the rabbit DRG 2 weeks after sham, continuous and PRF, illustrated no pathological findings in control and sham-operated group, minimal morphological changes in the PRF group, and neurodestruction in the continuous RF group. All these findings together
indicate that the effects of PRF are more reversible and less destructive than those of continuous RF, even when lesions are performed <45°C.
Despite the fact that PRF might operate by modulating pain perception rather than directly destroying neural tissue, at present it is difficult to relate the results of these experiences to clinical data. Little is known about how PRF procedures at frequencies and temperatures used in current clinical practice would modify central and peripheral components of pain pathways, and further well-designed in vitro and in vivo experiments are needed to clarify this issue. In addition, lesion parameters (sensory and motor stimulation
thresholds), electrode position, lesion duration, and local tissue properties can all be important variables that may influence clinical outcome.
In face of this laboratory evidence, a recent editorial urged practitioners to conduct randomized clinical trials to demonstrate the effectiveness (or lack thereof) of PRF treatment and only then use these data as a tool to understand and advance the technique. We find this statement troubling. Conducting sham-controlled RCTs in interventional pain management has been shown to have important methodological and ethical limitations. Randomized clinical trials have indeed become the gold standard for assessing the effectiveness of therapeutic agents, but often produce inconsistent results and can have limited external validity. Furthermore, Concato et al. and Concato and Horwitz have recently reported that the results of well designed observational studies do not systematically overestimate the magnitude of the effects when compared with randomized clinical trials.
Conclusions
Animal data suggest that PRF, as an alternative mode to administer RF energy, has genuine differential biological effects in cell morphology, synaptic transmission, and pain signaling, which are minimally destructive and nontemperature dependent.
The clinical data on the use of PRF are progressively accumulating, and up to now no neurological complications are documented. In order to further elucidate the mode of action of PRF and to define its true value in the management of chronic pain, more research on this promising technique is justified.
September/October 2006 - Vol. 7 Issue 5 Page 369-470
ISIS Position Paper on Pulsed RF
Nikolai Bogduk
(396-407)
Discussion
There are stark differences between thermal RF lesioning techniques and pulsed RF treatment. 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, histologically verifiable tissue lesion, and there is no dispute of this being the objective of the procedure. There is strong evidence of outcome, not only with respect to relief of pain but also in terms of restoration of function and even resolution of psychological distress. The procedure has been vindicated by placebo-controlled trials. The relief of pain from properly performed RF neurotomy is profound. The benchmark is total relief of pain or nearly so. The nominal duration of relief is 1 year. Although pain may recur in some patients as the peripheral nerve regenerates, relief can be successfully reinstated by repeating the neurotomy.
What is clearly evident from the literature is that pulsed RF does not produce a lesion. Therefore, pulsed RF cannot be represented as a procedure resulting in nerve destruction, neurotomy, 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 thermal radiofrequency. It is not a substitute for thermal radiofrequency in conditions for which thermal radiofrequency has an established and proven efficacy. There is no evidence that pulsed radiofrequency replicates the efficacy of thermal radiofrequency. The available data indicate that pulsed radiofrequency is markedly inferior in these instances.
If pulsed radiofrequency is misrepresented as the same procedure or an equivalent alternative to thermal 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).
Pulsed radiofrequency is not equivalent to thermal radiofrequency. It is not a substitute for thermal radiofrequency in conditions for which thermal radiofrequency has an established and proven efficacy. There is no evidence that pulsed radiofrequency replicates the efficacy of thermal radiofrequency. The available data indicate that pulsed radiofrequency is markedly inferior in these instances.
If pulsed radiofrequency is misrepresented as the same procedure or an equivalent alternative to thermal 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).
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 placement of electrodes is not critical, this also renders pulsed RF a faster procedure than thermal RF. It would not be surprising, therefore, if some practitioners have adopted pulsed RF simply because it is a quicker, easier procedure.
Observer bias is probably another factor. Practitioners who adopt the procedure are likely to remember their successful cases, but forget the failures. Moreover, their impressions of the effectiveness 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 attenuation of effects over time. Under those conditions, a procedure with fair to reasonable short-term outcomes may look attractive. Only when longterm follow-up is conducted does the true effectiveness, or lack thereof, emerge.
Another factor that attracts practitioners to pulsed RF, especially those who have limited clinical experience or technical skill in percutaneous interventions, is the purported reduction or avoidance of side effects and complications associated with thermal RF, as the intent of pulsed RF is specifically 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 final attraction is financial. Pulsed RF becomes very attractive if it carries the same reimbursement 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 efficacy; pulsed RF does not.
• Using pulsed RF instead of thermal RF, where the latter is indicated, denies the patient the benefit 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 efficacy of thermal RF neurotomy unjustly impugns what should be an effective 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 of efficacy become available. Health care administrators must also understand that pulsed RF and thermal RF are different, nonequivalent procedures, having differing outcomes, and involving different degrees of medical risk, physician time and training.
Pulsed Radiofrequency Treatment: What Is the Evidence of Its
Effectiveness and Should It be Used in Clinical Practice?
Rollin M. Gallagher, MD, MPH, University of Pennsylvania, Philadelphia VA Medical Center, Pennsylvania, USA
(408-410)
Summary
Heretofore, critics understandably decried the lack of evidence for the clinical efficacy of PRF. Is this just another ballyhooed intervention that will drive costs higher without added benefit beyond existing treatments? PRF, if proven clinically effective, will surely find a place in our armamentarium because, compared with TRFN, PRF requires less precision in the placement of electrodes and is therefore faster to perform. Because tissue is not destroyed, it may be safer. Proponents tout its efficacy in controlling pain without actually destroying tissue, avoiding complications such as destruction of other sensory neurons and motor neurons. However, until recently, when Level 2&3 clinical evidence has been obtained, this enthusiasm is based upon testimonials of clinical experience rather than solid experimental evidence of the variety that convinces critics. The randomized, controlled clinical trial of Van Zundert et al., presented as IASP, begins the process of solidifying Level 3 and Level 4 evidence.
We owe it to our patients and the public to avoid stopping our use of this potentially valuable treatment as a "knee jerk" reaction to the lack of firm evidence. Rather, we should cautiously prescribe this promising intervention following clinical algorithms that are based upon the best clinical evidence available. However, it is critically important to avoid the mistake of creating a "carte blanche" environment for those practitioners who would abuse the privilege and opportunity presented by this new technology, besmirching our
credibility and ultimately impeding the opportunity to use this treatment to the benefit of the public. Ultimately, evidence, not reimbursement, should determine whether PRF finds a place in our clinical toolbox.
Pulsed Radiofrequency: Current Clinical and Biological Literature Available
Alex Cahana, Jan Van Zundert, Lucian Macrea, Maarten van Kleef, Menno Sluijter
(411-423)
Discussion
After an extensive literature search, we could detect 42 reports from 11 countries on the clinical use of percutaneous and transcutaneous PRF in different applications on a variety of (chronic) pain syndromes in 1,207 patients. Up till now in none of the listed reports, neurological side effects or complications with PRF were mentioned. Because this is a new technique, a substantial part of these results are reported in the abstract books of international scientific pain congresses. Their number is increasing yearly, and they are progressively published in peer-reviewed journals. This is a similar evolution to other techniques in medicine in general, and pain medicine in particular. Although there is an increasing focus in the literature for PRF, the question still remains: "What is its place in the pain management algorithm?"
In order to answer this question, it is important to understand the concept behind RF and PRF treatments. It is presumed that the mode of action of RF heat lesions is that by selectively heating nervous structures, denervation can impede nociceptive input. However, the observation that after RF treatment pain relief lasts longer than the sensory loss in the relevant dermatome, gave rise to the theory that heat is not the only mode of action and that other factors responsible for pain relief may be involved. Furthermore, the role of heat was further questioned after the results of Slappendel et al., who found no difference in patient outcome with RF treatment when an electrode tip temperature of 40°C was used compared with RF at 67°C. Thus, it was hypothesized that there must be another, perhaps additional, mechanism besides heat that alters pain signal transmission.
So PRF was conceived as a novel, potentially safer mode of administration of RF energy, whereby in 1 s, two bursts of 20 ms each of an alternating current are delivered. The oscillating frequency of the alternating current is 500,000 Hz. During one cycle, the "active phase" of 20 ms is followed by a "silent phase" of 480 ms to allow the generated heat to washout. The output is usually set at 45 V, but if the electrode tip temperature exceeds 42°C, the voltage is decreased.
In our review, we have shown that since the initial publication on PRF treatment for spinal pain in 1998, information from prospective and retrospective trials, as well as several case reports on the percutaneous use of PRF, is accumulating. Interestingly, the transcutaneous use of PRF, which is a different application, has been documented to provide good pain relief in different modes. The available information on PRF treatment does not allow pooling the data because of the differences in the reporting, but also because of the fact that the technical parameters such as voltage, impedance, time of application of the PRF current, and resulting electrode tip temperature are not always reported. There is an urgent need for a more standardized data collection and reporting.
In general, RF stimulation within frequencies between 300 Hz and 300 GHz create electric fields, which generate both current and heat on exposed biological substrates. It is clear that heat lesions of neural substrates above 45°C result in nonselective destruction of both myelinated and nonmyelinated nerve fibers. However, it has been shown that PRF and RF have differential neurobiological effects, aside from the heatinduced morphological changes; c-Fos activation, a marker for neuronal activity in the rat dorsal horn, has been reported to be expressed immediately (3 h) [84] and up to 7 days [85] after PRF treatment. The duration of Fos-like immunoreactivity exceeding the expected length of time for c-Fos expression caused by the acute effect of surgery and electrical stimulation of sensory nerves may be due to the inhibition of excitatory C-fiber responses as seen in long-term depression, according to an accompanying editorial [72]. Moreover, it has recently been reported that the biological effect of PRF was unlikely to be related to an overt thermal damage and appears to be selective in that it targets the group of neurons whose axons are the small-diameter C and Aδ nociceptive fibers.
We also found that PRF alters synaptic transmission. In vitro PRF stimuli of organotypic slices of the hippocampus induce transient decrease in excitatory postsynaptic potential with rapid and complete recovery, while in contrast, continuous RF creates long-lasting blockade of synaptic transmission even in temperatures <45°C. Both continuous and PRF treatments induce distancedependent tissue destruction under the stimulating needle, but the effect was more pronounced in the continuous group. Similarly, a morphological evaluation of the rabbit DRG 2 weeks after sham, continuous and PRF, illustrated no pathological findings in control and sham-operated group, minimal morphological changes in the PRF group, and neurodestruction in the continuous RF group. All these findings together
indicate that the effects of PRF are more reversible and less destructive than those of continuous RF, even when lesions are performed <45°C.
Despite the fact that PRF might operate by modulating pain perception rather than directly destroying neural tissue, at present it is difficult to relate the results of these experiences to clinical data. Little is known about how PRF procedures at frequencies and temperatures used in current clinical practice would modify central and peripheral components of pain pathways, and further well-designed in vitro and in vivo experiments are needed to clarify this issue. In addition, lesion parameters (sensory and motor stimulation
thresholds), electrode position, lesion duration, and local tissue properties can all be important variables that may influence clinical outcome.
In face of this laboratory evidence, a recent editorial urged practitioners to conduct randomized clinical trials to demonstrate the effectiveness (or lack thereof) of PRF treatment and only then use these data as a tool to understand and advance the technique. We find this statement troubling. Conducting sham-controlled RCTs in interventional pain management has been shown to have important methodological and ethical limitations. Randomized clinical trials have indeed become the gold standard for assessing the effectiveness of therapeutic agents, but often produce inconsistent results and can have limited external validity. Furthermore, Concato et al. and Concato and Horwitz have recently reported that the results of well designed observational studies do not systematically overestimate the magnitude of the effects when compared with randomized clinical trials.
Conclusions
Animal data suggest that PRF, as an alternative mode to administer RF energy, has genuine differential biological effects in cell morphology, synaptic transmission, and pain signaling, which are minimally destructive and nontemperature dependent.
The clinical data on the use of PRF are progressively accumulating, and up to now no neurological complications are documented. In order to further elucidate the mode of action of PRF and to define its true value in the management of chronic pain, more research on this promising technique is justified.
