- Email: [email protected]
Radiofrequency vs. pulse radiofrequency: The end of the controversy
Techniques in Regional Anesthesia and Pain Management (2010) 14, 128-132
Radiofrequency vs. pulse radiofrequency: The end of the controversy Ricardo Vallejo, MD, PhD, FIPP,a,b,c Ramsin M. Benyamin, MD,a,c,d Luis Aliaga, MDc From the aMillennium Pain Center, Bloomington, Illinois; b Department of Biological Sciences, Illinois State University, Normal, Illinois; c Clinica del Dolor, Teknon, Barcelona, Spain; and the d Department of Surgery, University of Illinois, College of Medicine, Champaign, Illinois. KEYWORDS: Radiofrequency; Pulse radiofrequency; Denervation; Neuromodulation
Radiofrequency (RF) denervation is a percutaneous procedure involving the destruction of nerves using heat generated by a RF current (thermal RF) or neuromodulation of nerve electrical conduction. Current evidence strongly supports thermal RF for the treatment of trigeminal neuralgia, cervical and lumbar facet spondylosis, and sacroiliac joint pain. Despite the popularity of this technique, comparative efficacy studies have failed to support the use of PRF for the abovementioned indications. However, these comparative studies have often targeted those sites commonly addressed and proven efficacious by thermal RF. In contrast, PRF might prove more valuable in modulating nerve conduction in other pain syndromes, such as neuropathic pain conditions. At present, only anecdotal evidence is available on the use of PRF in these conditions. As thermal RF, by definition, is contraindicated in neuropathic pain syndromes, it seems that the two techniques are essentially different and the indications for PRF still need to be defined. © 2010 Elsevier Inc. All rights reserved.
Radiofrequency (RF) denervation is a percutaneous procedure involving the destruction of nerves using heat generated by a RF current. Originally, a direct electrical current was used to create the thermal lesions, but the erratic nature of the current caused by electrolysis created an unpredictable lesion that eventually led to the abandonment of this technique. In the 1950s, the first commercially available, alternating current, RF generators were introduced. The term “radiofrequency” is derived from the high-frequency (⬃500 kHz) electromagnetic radiation, in the same range used by an AM radio signal, which was employed in the generators. The basic principles of RF involve transferring an alternating electrical current, in the same frequency range as Address reprint requests and correspondence: Ricardo Vallejo, MD, PhD, FIPP, Millennium Pain Center, 1015 South Mercer Avenue, Bloomington, IL 61701. E-mail address: [email protected].
1084-208X/$ -see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1053/j.trap.2010.06.003
radio waves, by a generator to a nerve via an active electrode. The electrode is introduced through an insulated needle, with the exposed “active” tip transferring the current to the surrounding tissues. The current is captured by a grounding pad and transferred back to the generator, closing the electrical circuit. The high current density created at the tip of the needle generates molecular oscillation of the tissues, resulting in an increase in temperature. The elements of the RF device include the RF generator itself, the shielded needle electrode, a thermocouple, impedance monitor, and a nerve stimulator. The thermocouple component allows the monitoring of tissue temperature at the tip of the needle. The pattern of heat distribution around the tip of the needle is pear-shaped, with the widest diameter proximal from the tip and the smaller diameter more distal. Therefore, the tip of the needle should be parallel to the targeted nerve. Tissue coagulation is observed at temperatures above 60°C. If the tem-
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RF vs. PRF
perature around the needle is maintained between 80 and 85°C, tissue within several millimeters of the needle tip will reach 60°C or higher. As a general rule, it could be assumed that coagulation temperatures will be achieved within approximately two electrode-widths from the surface of the electrode. Another important component of the RF system is the impendence monitor. Impedance is defined as the ratio of voltage to current (or electrical field strength to magnetic field strength) and is measured in ohms (⍀). Impedance monitoring, as a measure of resistivity of tissue, assists the practitioner in properly locating the needle electrode, as blood, tissue, and bone have differing resistivities, and ensures that the electrical delivery is performing properly; a sudden rise in impedance typically indicates coagulum formation and tissue charring and is an indication to stop RF. If the tip of the needle is in extradural tissues, the impedance will be around 300-600 ⍀, whereas if the needle is intradural, the impedance will be very low. The impedance will increase to a higher level at the end of the lesioning. As nerve fibers are not visible using fluoroscopy, the introducer needle is positioned using bony landmarks. The nerve stimulator is employed to positively identify the correct needle position. When used at 50 Hz, sensory nerve fibers are activated. As the voltage increases, the patient may feel a paresthesia or deep ache that will serve as a guide as how far the needle is to the targeted nerve. For example, if the patient perceives paresthesias at 0.25 V, the electrode is on the nerve. By contrast, perception of stimulation at greater than 2 V implies that the electrode is at least 1 cm distant from the nerve. Nerve stimulation at 2 Hz is used to activate motor nerve fibers. During this type of stimulation, the patient may feel some twitching or throbbing, but no large muscle groups should be stimulated. At least three times the sensory threshold should be administered to ensure that motor fibers are not lesioned. The first reported clinical use of RF was to treat trigeminal neuralgia and was described by Sweet in 1974.1 The positive results with this procedure encouraged the application of RF to target different structures. Next, RF was used in patients with terminal cancer who underwent destruction of the anteriolateral spinothalamic tract at the C2 level to disrupt pain transmission.2 As the technique became more popular, further indications were advanced. One of those targeted structures were the zygopophysial joints of the lumbar and cervical spines. The thermal lesion was aimed at the medial branches of the dorsal rami that innervate the facet. Later, the use of RF extended to the treatment of many other painful conditions. Among them, the dorsal root ganglion (DRG) seemed an obvious target to treat radicular pain. Because of concerns about potential damage to motor nerve fibers, the temperatures applied were lower (around 65°C) and the needle tips were positioned more distant from the nerves. Inconsistent results with this technique led to the concept that an electrical field, created at the tip of the needle and not temperature, was the cause of the observed results. Based on this assumption, a variant of this technique
129 was devised where an alternating current was applied in short bursts, spaced by silent intervals that allowed heat to dissipate. Thermal RF produces initial massive edema followed by dramatic Wallerian degeneration within 7 days, whereas only mild edema is observed when the temperature is maintained below 42°C.3 This therapy was named pulse radiofrequency (PRF). Numerous case reports and a number of larger case series using PRF have been published. However, few randomized, controlled studies support the efficacy of this technique. In this article, we will review the evidence for the use of RF, focusing on the current controversy between the use of the conventional (thermal) RF and the new therapeutic modality, PRF.
Thermal radiofrequency: indications and evidence Trigeminal neuralgia Thermal RF has been extensively used for the treatment of tic douloureux or trigeminal neuralgia. The most common etiology of this neuralgia is compression of the 5th (trigeminal) cranial nerve at the brainstem by a vascular structure or mass lesion. Medical pharmacologic treatment is frequently successful, but 10%-30% of cases do not respond to conservative management. A therapeutic option for these patients includes microvascular decompression, an invasive surgical option with an 80% success rate but a recurrence rate of 10%-20%.4 Percutaneous thermal RF of the gasserian ganglion is a less invasive option offering complete pain relief in up to 80% of patients.5 When compared with other minimally invasive options, such as gamma knife, glycerol injection, or percutaneous balloon decompression, thermal RF has the highest rates of complete relief.6 However, complications are not uncommon.6 The most common of these complications is mild facial numbness (98%), followed by reduced corneal reflexes (17%), profound numbness (10%), abolition of corneal reflex (3%), masticatory weakness (3%), ulcerative keratitis (1.9%), and anesthesia dolorosa (1.5%).7
Cervical facet arthropathy Another recognized indication for the use of thermal RF is the treatment of cervical facet joint pain. Cervical zygapophysial joint pain is common in patients with chronic neck pain. In 1996, Lord and Bogduk demonstrated a 60% incidence of facet joint pain in patients after whiplash injury.8 The same authors, with a group of 24 patients in a randomized, double-blind, placebo-controlled study, evaluated the efficacy of thermal RF of the cervical medial branches versus placebo. To be considered successful, the patients had to report 100% pain relief. The active group, but not the placebo, reported short- and long-term pain
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relief, with an average of 263 days for pain to return to 50% in the active group and 8 days in the placebo group.9 Sapir and Gorup, in an observational study, evaluated the efficacy of cervical facet medial branch thermal RF in patients with chronic neck pain. The patients underwent double diagnostic blocks, and successful outcome was defined as 80% relief of pain. At 1-year follow-up, numeric rating scale scores dropped from an average of 8.2-3.6.10 McDonald, Lord, and Bogduk followed 20 patients with cervical zygapophyseal joint pain who underwent thermal RF resulting in complete pain relief in 71% of the patients after the initial RF procedure over a 6-year period.11 Including patients who failed to respond to treatment, the median duration of relief after the first procedure was still 219 days. The average duration of pain relief was 422 days in those patients who initially responded to treatment. Barnsley compiled 47 procedures performed on 35 patients. In 36 of the 45 assessable procedures, 80% achieved significant pain relief for up to 36 weeks.12 In a recent systematic review by the American Society of Interventional Pain Physicians (ASIPP), the previously described studies were analyzed. Evaluating the quantitative evidence according to guidelines developed by United States Preventative Services Task Force, ASIPP resolved that there is good quality evidence to support the use of thermal RF on the cervical median branch.13
Lumbar facet medial branch neurotomy The spinal facet joints are potential generators of low back pain, presumably mediated by the medial branch nerves. Lumbar zygopophyseal joint syndrome has a prevalence of 15%-52% in the population of patients with chronic low back pain. Facet diagnostic injection has become the gold standard for diagnosing zygopophyseal joint pain. There are multiple studies evaluating the efficacy of lumbar facet thermal RF in the treatment of lumbar spondylosis. Gallagher and coworkers, in a double-blind, randomized, controlled trial, evaluated the efficacy of thermal RF compared with sham procedure. Follow-up at 1 and 6 months showed significantly better results in the thermal RF group.14 In 1999, Van Kleef and colleagues,15 in a doubleblind, randomized study of thermal RF lumbar facet denervation versus sham, observed a positive response in treated patients with a number needed-to-treat (NNT) of 1.6 at 12-month follow-up. Two years later, Leclaire and coworkers16 evaluated functional disability outcomes in 70 patients following thermal RF facet joint denervation. To diagnose the facet arthropathy, they performed intra-articular injections. Interestingly, positive responses were obtained from 70 of 76 patients screened (92% prevalence). Because the frequency of this pathology in patients with chronic lumbar pain is considerably below that level, the results of this study are questionable. In this study, the NNT was 11. The validity of a double-blind, randomized study by Van Wijk and coworkers17 has been questioned due to technical prob-
lems and concerns about whether the placebo group was or was not an active intervention. The NNT was 3.6. In a more recent study, Nath and coworkers performed a double-blind, randomized, controlled study in 40 patients.18 To confirm the diagnosis, they performed 3 medial branch diagnostic blocks. The patients were then randomized to a sham procedure versus thermal RF neurotomy. Evaluated outcomes included visual analog score (VAS), quality of life, and global perceived effect. At 6-month follow-up, strong improvement was seen in the active group. A recent systematic review by the ASIPP strongly supported the evidence for thermal RF facet joint neurotomy for short-term and longterm pain relief.19
Thermal radiofrequency of the dorsal root ganglion Encouraged by the positive results using thermal RF for the previously mentioned indications, the DRG became a target to treat patients with radicular symptoms. As described by Van Kleef, “The procedure is intended to expose the DRG to temperatures that prevail in the peripheral part of an RF lesion to preserve the large myelinated fibers and to deactivate the small myelinated fibers.”20 Several studies have been published, and the results have been mixed. Van Wijk and coworkers treated 270 patients prospectively with a diagnosis of lumbosacral pain. The median duration of pain relief was 44 weeks in 59% of the patients.21 They evaluated the efficacy of thermal RF of the lumbosacral DRG after selective nerve root block. In 1997, concerns about whether high temperature was a cause of poor outcome led Slappendel to compare the effects of thermal RF of the DRG in patients exposed to 40°C to those exposed to 67°C treatments.22 Patients were followed at 6 weeks and 3 months. Interestingly, although data revealed that neither group of patients obtained significant relief when compared with baseline, the concept that high temperature was unnecessary was born and led to the development of the PRF technique.
Sacroiliac joint pain Sacroiliac joint pain may affect up to 20% of patients with chronic low back pain. Cohen and coworkers23 performed a randomized, placebo-controlled study in 28 patients diagnosed with sacroiliac joint pain by intra-articular diagnostic injection. Fourteen patients received thermal RF denervation of the L4 medial branch, L5 posterior primary rami, and the lateral branches of S1, S2, and S3, whereas the other 14 patients underwent local anesthetic blocks and served as controls. Patients were followed at 1, 3, and 6 months postprocedure. Treatment success was considered when at least 50% pain relief was obtained. At 1-month follow-up, 79% of the active group had significant relief, and the benefit was maintained in 57% of patients at 6-month follow-up. Unfortunately, only 14% of the patients
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followed at 1 year postprocedure still experienced relief. Based on these preliminary results, sacroiliac denervation of the sacroiliac joint seems like a good option for patients refractory to other treatments.23
Pulsed radiofrequency In contrast with thermal RF, PRF is a nondestructive procedure, where electrical bursts of 20 msecond of electricity are applied followed by 480 msecond of no current to allow heat to dissipate, to keep the tissue temperature below 42°C. The concept behind it is that an electrical field spreading from the tip of the needle electrode will modulate nerve electrical conduction providing similar results to conventional thermal RF. Despite the popularity of this technique, there is little clinical evidence that strongly supports its use. In recent years, some animal studies have evaluated the potential mechanism of action of PRF. Cahana And coworkers, in an in vitro study, observed glial cell proliferation after hypocampus cells where exposed to PRF.24 Two different studies evaluated c-fos activation after PRF of the C6 DRG. It was interesting to observe that two different studies with similar methodologies observed different results. Yoshinori and colleagues25 observed c-fos activation in the dorsal horn with PRF but not thermal RF at 42°C, whereas Van Zundert observed similar effects in both groups.26 Recently, Hagiwara and coworkers27 elucidated the potential effect of PRF on the norepinephrine and serotonin systems after observing marked inhibition of the analgesic effect of PRF after the administration of specific neurotransmitter antagonists. Clinically, there are a large number of case reports and case series but few convincing randomized, controlled trials that support the use of PRF. Van Zundert and coworkers28 performed PRF of the trigeminal ganglion in 5 patients with pain refractory to conservative treatment. He followed them for 19 months and observed excellent pain relief in 3 patients, partial pain relief in 1, and no pain relief in the last patient.28 He even performed thermal RF on the nonresponsive patient, again with no success. The same group did PRF adjacent to the cervical DRG for patients with chronic cervical radicular pain in a double-blind, sham-controlled, randomized study.29 At 3 months and 6 months, they observed a statistical difference between the groups with improvements in global perception of effect and numeric rating and VAS with a trend toward improvement in quality of life in the PRF group.29 Since then, multiple case series have been published, suggesting a beneficial effect in conditions ranging from postherpetic neuralgia30,31 and sacroiliac joint pain32,33 to radicular low back pain.34 In a prospective case series, Vallejo and coworkers32 evaluated the efficacy of PRF in the treatment of sacroiliac joint pain by treating similar branches as the Cohen and coworkers series of patients treated with thermal RF. Twenty-two patients who had failed to respond to conservative treatment and intra-
131 articular steroid injections underwent PRF. Seventy-two percent of the patients reported 50% or better pain relief with a mean duration of the effect lasting 6-9 weeks in 4 patients, 10-16 weeks in 5 patients and 17-32 weeks 7 patients.32 Abejón and coworkers34 retrospectively evaluated the efficacy of PRF in patients with lumbar radicular pain. Prior to PRF, all patients had at least 50% pain relief with a single nerve root block. He then performed 75 PRFs in 54 patients. He observed significant improvement in global perception of effect in patients with herniated disks and spinal stenosis, whereas patients with failed back surgery syndrome did not achieve statistical improvement.34 Kim and coworkers31 performed PRF on the DRG on 49 patients with postherpetic neuralgia. Levels treated included 61% thoracic, 24% cervical, and 14% lumbar. At 12-week follow-up, the mean VAS dropped from 7.2 at baseline to 3.1.31
Comparative efficacy between conventional and thermal radiofrequency A prospective, randomized, double-blind study evaluated the efficacy of PRF versus thermal RF in patients with trigeminal neuralgia.35 Forty patients with similar demographics were randomized between the 2 groups. Evaluated outcomes included VAS, patient satisfaction scale, additional pharmacologic treatment, as well as side effects and complications. Only the thermal RF group achieved a statistically significant improvement in VAS and patient satisfaction scale. Only 2 of 20 patients in the PRF group had decreased VAS scores, but pain recurred in both of them at the 3-month follow-up. After 3 months, patients were allowed to crossover to thermal RF, and once again significant improvements were seen. The authors concluded that PRF is not an effective method of pain treatment for idiopathic trigeminal neuralgia.35 Two other comparative studies have assessed the benefit of these two techniques in patients with lumbar facet arthropathy.36,37 Tekin and coworkers,36 in a double-blind, randomized, controlled trial and following a single diagnostic block, randomized 60 patients between PRF, thermal RF, and local anesthetic injection. Patients were evaluated at 6 and 12 months. Only the thermal RF group showed a statistical benefit when compared with control.36 A similar study evaluated 50 patients and observed a decrease in VAS and improvement in disability that was statistically significant only in the thermal RF group. Follow-up was carried for only 3 months, and a major weakness of the study was a drop-out rate of 48% of patients.37
Conclusions Current evidence strongly supports thermal RF for the treatment of trigeminal neuralgia, cervical and lumbar facet spondylosis, and sacroiliac joint pain. Comparative efficacy
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studies have failed to support the use of PRF for the abovementioned indications. However, these comparative studies have often targeted those sites commonly addressed and proven efficacious by thermal RF. In contrast, PRF might prove more valuable in modulating nerve conduction in other pain syndromes, such as neuropathic pain conditions. As thermal RF, by definition, is contraindicated in neuropathic pain syndromes, it seems that the two techniques are essentially different and the indications for PRF still need to be defined.
References 1. Sweet WH, Wepsic JG: Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers. 1. Trigeminal neuralgia. J Neurosurg 40:143-156, 1974 2. Rosomoff HL, Brown CJ, Sheptak P: Percutaneous radiofrequency cervical cordotomy: technique. J Neurosurg 23:639-644, 1965 3. Podhajsky RJ, Sekiguchi Y, Kikuchi S, et al: The histologic effects of pulsed and continuous radiofrequency lesions at 42 degrees C to rat dorsal root ganglion and sciatic nerve. Spine 30:1008-1013, 2005 4. Sanchez-Mejia RO, Limbo M, Cheng JS, et al: Recurrent or refractory trigeminal neuralgia after microvascular decompression, radiofrequency ablation, or radiosurgery. Neurosurg Focus 18:e12, 2005 5. Lord SM, Bogduk N: Radiofrequency procedures in chronic pain. Best Pract Res Clin Anaesthesiol 16:597-617, 2002 6. Lopez BC, Hamyn PJ, Zakrzewska JM: Systematic review of ablative neurosurgical techniques for the treatment of trigeminal neuralgia. Neurosurgery 54:973-982, 2004 7. Fraioli B, Esposito V, Guidetti B, et al: Treatment of trigeminal neuralgia by thermocoagulation, glycerolization, and percutaneous compression of the gasserian ganglion and/or retrogasserian rootlets: long-term results and therapeutic protocol. Neurosurgery 24:239-245, 1989 8. Lord SM, Barnsley L, Wallis BJ, et al: Chronic cervical zygapophysial joint pain after whiplash. A placebo-controlled prevalence study. Spine 21:1737-1744, discussion 1744-1745, 1996 9. Lord SM, Barnsley L, Wallis BJ, et al: Percutaneous radiofrequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med 335:1721-1726, 1996 10. Sapir DA, Gorup JM: Radiofrequency medial branch neurotomy in litigant and nonlitigant patients with cervical whiplash: a prospective study. Spine 26:E268-E273, 2001 11. McDonald GJ, Lord SM, Bogduk N: Long-term follow-up of patients treated with cervical radiofrequency neurotomy for chronic neck pain. Neurosurgery 45:61-67, 1999 12. Barnsley L: Percutaneous radiofrequency neurotomy for chronic neck pain: outcomes in a series of consecutive patients. Pain Med 6:282-286, 2005 13. Falco FJ, Erhart S, Wargo BW, et al: Systematic review of diagnostic utility and therapeutic effectiveness of cervical facet joint interventions. Pain Physician 12:323-344, 2009 14. Gallagher J, Petriccione De Vadi PL, et al: Radiofrequency facet joint denervation in the treatment of low back pain: a prospective controlled double-blind study to assess its efficacy. Pain Clin 7:193-198, 1994 15. Van Kleef M, Barendse GA, Kessels A, et al: Randomized trial of radiofrequency lumbar facet denervation for chronic low back pain. Spine 24:1937-1942, 1999 16. Leclaire R, Fortin L, Lambert R, et al: Radiofrequency facet joint denervation in the treatment of low back pain: a placebo-controlled clinical trial to assess efficacy. Spine 26:1411-1417, 2001 17. Van Wijk RM, Geurts JW, Wynne HJ, et al: Radiofrequency denervation of lumbar facet joints in the treatment of chronic low back pain: a randomized, double-blind, sham lesion-controlled trial. Clin J Pain 21:335-344, 2005
18. Nath S, Nath CA, Pettersson K: Percutaneous lumbar zygapophysial (facet) joint neurotomy using radiofrequency current, in the management of chronic low back pain: a randomized double-blind trial. Spine 33:1291-1298, 2008 19. Datta S, Lee M, Falco FJ, et al: Systematic assessment of diagnostic accuracy and therapeutic utility of lumbar facet joint interventions. Pain Physician 12:437-460, 2009 20. Van Kleef M, Barendse G, Sluijter M: Response: assessing a new procedure: thoracic radiofrequency dorsal root ganglion lesions. Clin J Pain 12:77-78, 1996 21. van Wijk RM, Geurts JW, Wynne HJ: Long-lasting analgesic effect of radiofrequency treatment of the lumbosacral dorsal root ganglion. J Neurosurg 94:227-231, 2001 (suppl) 22. Slappendel R, Crul BJ, Braak GJ, et al: The efficacy of radiofrequency lesioning of the cervical spinal dorsal root ganglion in a double blinded randomized study: no difference between 40 degrees C and 67 degrees C treatments. Pain 73:159-163, 1997 23. Cohen SP, Hurley RW, Buckenmaier CC 3rd, et al: Randomized placebo-controlled study evaluating lateral branch radiofrequency denervation for sacroiliac joint pain. Anesthesiology 109:279-288, 2008 24. Cahana A, Vutskits L, Muller D: The differential modulation of synaptic transmission and cell survival during exposure to pulsed and continuous radiofrequency energy. J Pain 4:197-202, 2003 25. Higuchi Y, Nashold BS Jr, Sluijter M, et al: Exposure of the dorsal root ganglion in rats to pulsed radiofrequency currents activates dorsal horn lamina I and II neurons. Neurosurgery 50:850-856, 2002 26. Van Zundert J, de Louw AJ, Joosten EA, et al: Pulsed and continuous radio frequency current adjacent to the cervical dorsal root ganglion of the rat induces late cellular activity in the dorsal horn. Anesthesiology 102:125-131, 2005 27. Hagiwara S, Iwasaka H, Takeshima N, et al: Mechanisms of analgesic action of pulsed radiofrequency on adjuvant-induced pain in the rat: roles of descending adrenergic and serotonergic systems. Eur J Pain 13:249-252, 2009 28. Zundert J, Brabant S, Van de Kelft E, et al: Pulsed radiofrequency treatment of the Gasserian ganglion in patients with idiopathic trigeminal neuralgia. Pain 104:449-452, 2003 29. Van Zundert J, Patijn J, Kessels A, et al: Pulsed radiofrequency adjacent to the cervical dorsal root ganglion in chronic cervical radicular pain: a double blind sham controlled randomized clinical trial. Pain 127:173-182, 2007 30. Huang B, Zhou XY, Lu YP, et al: Selective percutaneous dorsal root ganglion radiofrequency thermocoagulation guided by CT scanning in treatment of post-herpetic neuralgia. Zhonghua Yi Xue Za Zhi 88:885888, 2008 31. Kim YH, Lee CJ, Lee SC, et al: Effect of pulsed radiofrequency for postherpetic neuralgia. Acta Anaesthesiol Scand 52:1140-1143, 2008 32. Vallejo R, Benyamin RM, Kramer J, et al: Pulsed radiofrequency denervation for the treatment of sacroiliac joint syndrome. Pain Med 7:429-434, 2006 33. Rhame EE, Levey KA, Gharibo CG: Successful treatment of refractory pudendal neuralgia with pulsed radiofrequency. Pain Physician 12: 633-638, 2009 34. Abejón D, Garcia-del-Valle S, Fuentes ML, et al: Pulsed radiofrequency in lumbar radicular pain: clinical effects in various etiological groups. Pain Pract 7:21-26, 2007 35. Erdine S, Ozyalcin NS, Cimen A, et al: Comparison of pulsed radiofrequency with conventional radiofrequency in the treatment of idiopathic trigeminal neuralgia. Eur J Pain 11:309-313, 2007 36. Tekin I, Mirzai H, Ok G, et al: A comparison of conventional and pulsed radiofrequency devervation in the treatment of chronic facet joint pain. Clin J Pain 23:524-529, 2007 37. Kroll HR, Kim D, Danic MJ, et al: A randomized, double-blind, prospective study comparing the efficacy of continuous versus pulsed radiofrequency in the treatment of lumbar facet syndrome. J Clin Anesth 20:534-537, 2008
Radiofrequency vs. pulse radiofrequency: The end of the controversy Ricardo Vallejo, MD, PhD, FIPP,a,b,c Ramsin M. Benyamin, MD,a,c,d Luis Aliaga, MDc From the aMillennium Pain Center, Bloomington, Illinois; b Department of Biological Sciences, Illinois State University, Normal, Illinois; c Clinica del Dolor, Teknon, Barcelona, Spain; and the d Department of Surgery, University of Illinois, College of Medicine, Champaign, Illinois. KEYWORDS: Radiofrequency; Pulse radiofrequency; Denervation; Neuromodulation
Radiofrequency (RF) denervation is a percutaneous procedure involving the destruction of nerves using heat generated by a RF current (thermal RF) or neuromodulation of nerve electrical conduction. Current evidence strongly supports thermal RF for the treatment of trigeminal neuralgia, cervical and lumbar facet spondylosis, and sacroiliac joint pain. Despite the popularity of this technique, comparative efficacy studies have failed to support the use of PRF for the abovementioned indications. However, these comparative studies have often targeted those sites commonly addressed and proven efficacious by thermal RF. In contrast, PRF might prove more valuable in modulating nerve conduction in other pain syndromes, such as neuropathic pain conditions. At present, only anecdotal evidence is available on the use of PRF in these conditions. As thermal RF, by definition, is contraindicated in neuropathic pain syndromes, it seems that the two techniques are essentially different and the indications for PRF still need to be defined. © 2010 Elsevier Inc. All rights reserved.
Radiofrequency (RF) denervation is a percutaneous procedure involving the destruction of nerves using heat generated by a RF current. Originally, a direct electrical current was used to create the thermal lesions, but the erratic nature of the current caused by electrolysis created an unpredictable lesion that eventually led to the abandonment of this technique. In the 1950s, the first commercially available, alternating current, RF generators were introduced. The term “radiofrequency” is derived from the high-frequency (⬃500 kHz) electromagnetic radiation, in the same range used by an AM radio signal, which was employed in the generators. The basic principles of RF involve transferring an alternating electrical current, in the same frequency range as Address reprint requests and correspondence: Ricardo Vallejo, MD, PhD, FIPP, Millennium Pain Center, 1015 South Mercer Avenue, Bloomington, IL 61701. E-mail address: [email protected].
1084-208X/$ -see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1053/j.trap.2010.06.003
radio waves, by a generator to a nerve via an active electrode. The electrode is introduced through an insulated needle, with the exposed “active” tip transferring the current to the surrounding tissues. The current is captured by a grounding pad and transferred back to the generator, closing the electrical circuit. The high current density created at the tip of the needle generates molecular oscillation of the tissues, resulting in an increase in temperature. The elements of the RF device include the RF generator itself, the shielded needle electrode, a thermocouple, impedance monitor, and a nerve stimulator. The thermocouple component allows the monitoring of tissue temperature at the tip of the needle. The pattern of heat distribution around the tip of the needle is pear-shaped, with the widest diameter proximal from the tip and the smaller diameter more distal. Therefore, the tip of the needle should be parallel to the targeted nerve. Tissue coagulation is observed at temperatures above 60°C. If the tem-
Vallejo et al
RF vs. PRF
perature around the needle is maintained between 80 and 85°C, tissue within several millimeters of the needle tip will reach 60°C or higher. As a general rule, it could be assumed that coagulation temperatures will be achieved within approximately two electrode-widths from the surface of the electrode. Another important component of the RF system is the impendence monitor. Impedance is defined as the ratio of voltage to current (or electrical field strength to magnetic field strength) and is measured in ohms (⍀). Impedance monitoring, as a measure of resistivity of tissue, assists the practitioner in properly locating the needle electrode, as blood, tissue, and bone have differing resistivities, and ensures that the electrical delivery is performing properly; a sudden rise in impedance typically indicates coagulum formation and tissue charring and is an indication to stop RF. If the tip of the needle is in extradural tissues, the impedance will be around 300-600 ⍀, whereas if the needle is intradural, the impedance will be very low. The impedance will increase to a higher level at the end of the lesioning. As nerve fibers are not visible using fluoroscopy, the introducer needle is positioned using bony landmarks. The nerve stimulator is employed to positively identify the correct needle position. When used at 50 Hz, sensory nerve fibers are activated. As the voltage increases, the patient may feel a paresthesia or deep ache that will serve as a guide as how far the needle is to the targeted nerve. For example, if the patient perceives paresthesias at 0.25 V, the electrode is on the nerve. By contrast, perception of stimulation at greater than 2 V implies that the electrode is at least 1 cm distant from the nerve. Nerve stimulation at 2 Hz is used to activate motor nerve fibers. During this type of stimulation, the patient may feel some twitching or throbbing, but no large muscle groups should be stimulated. At least three times the sensory threshold should be administered to ensure that motor fibers are not lesioned. The first reported clinical use of RF was to treat trigeminal neuralgia and was described by Sweet in 1974.1 The positive results with this procedure encouraged the application of RF to target different structures. Next, RF was used in patients with terminal cancer who underwent destruction of the anteriolateral spinothalamic tract at the C2 level to disrupt pain transmission.2 As the technique became more popular, further indications were advanced. One of those targeted structures were the zygopophysial joints of the lumbar and cervical spines. The thermal lesion was aimed at the medial branches of the dorsal rami that innervate the facet. Later, the use of RF extended to the treatment of many other painful conditions. Among them, the dorsal root ganglion (DRG) seemed an obvious target to treat radicular pain. Because of concerns about potential damage to motor nerve fibers, the temperatures applied were lower (around 65°C) and the needle tips were positioned more distant from the nerves. Inconsistent results with this technique led to the concept that an electrical field, created at the tip of the needle and not temperature, was the cause of the observed results. Based on this assumption, a variant of this technique
129 was devised where an alternating current was applied in short bursts, spaced by silent intervals that allowed heat to dissipate. Thermal RF produces initial massive edema followed by dramatic Wallerian degeneration within 7 days, whereas only mild edema is observed when the temperature is maintained below 42°C.3 This therapy was named pulse radiofrequency (PRF). Numerous case reports and a number of larger case series using PRF have been published. However, few randomized, controlled studies support the efficacy of this technique. In this article, we will review the evidence for the use of RF, focusing on the current controversy between the use of the conventional (thermal) RF and the new therapeutic modality, PRF.
Thermal radiofrequency: indications and evidence Trigeminal neuralgia Thermal RF has been extensively used for the treatment of tic douloureux or trigeminal neuralgia. The most common etiology of this neuralgia is compression of the 5th (trigeminal) cranial nerve at the brainstem by a vascular structure or mass lesion. Medical pharmacologic treatment is frequently successful, but 10%-30% of cases do not respond to conservative management. A therapeutic option for these patients includes microvascular decompression, an invasive surgical option with an 80% success rate but a recurrence rate of 10%-20%.4 Percutaneous thermal RF of the gasserian ganglion is a less invasive option offering complete pain relief in up to 80% of patients.5 When compared with other minimally invasive options, such as gamma knife, glycerol injection, or percutaneous balloon decompression, thermal RF has the highest rates of complete relief.6 However, complications are not uncommon.6 The most common of these complications is mild facial numbness (98%), followed by reduced corneal reflexes (17%), profound numbness (10%), abolition of corneal reflex (3%), masticatory weakness (3%), ulcerative keratitis (1.9%), and anesthesia dolorosa (1.5%).7
Cervical facet arthropathy Another recognized indication for the use of thermal RF is the treatment of cervical facet joint pain. Cervical zygapophysial joint pain is common in patients with chronic neck pain. In 1996, Lord and Bogduk demonstrated a 60% incidence of facet joint pain in patients after whiplash injury.8 The same authors, with a group of 24 patients in a randomized, double-blind, placebo-controlled study, evaluated the efficacy of thermal RF of the cervical medial branches versus placebo. To be considered successful, the patients had to report 100% pain relief. The active group, but not the placebo, reported short- and long-term pain
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relief, with an average of 263 days for pain to return to 50% in the active group and 8 days in the placebo group.9 Sapir and Gorup, in an observational study, evaluated the efficacy of cervical facet medial branch thermal RF in patients with chronic neck pain. The patients underwent double diagnostic blocks, and successful outcome was defined as 80% relief of pain. At 1-year follow-up, numeric rating scale scores dropped from an average of 8.2-3.6.10 McDonald, Lord, and Bogduk followed 20 patients with cervical zygapophyseal joint pain who underwent thermal RF resulting in complete pain relief in 71% of the patients after the initial RF procedure over a 6-year period.11 Including patients who failed to respond to treatment, the median duration of relief after the first procedure was still 219 days. The average duration of pain relief was 422 days in those patients who initially responded to treatment. Barnsley compiled 47 procedures performed on 35 patients. In 36 of the 45 assessable procedures, 80% achieved significant pain relief for up to 36 weeks.12 In a recent systematic review by the American Society of Interventional Pain Physicians (ASIPP), the previously described studies were analyzed. Evaluating the quantitative evidence according to guidelines developed by United States Preventative Services Task Force, ASIPP resolved that there is good quality evidence to support the use of thermal RF on the cervical median branch.13
Lumbar facet medial branch neurotomy The spinal facet joints are potential generators of low back pain, presumably mediated by the medial branch nerves. Lumbar zygopophyseal joint syndrome has a prevalence of 15%-52% in the population of patients with chronic low back pain. Facet diagnostic injection has become the gold standard for diagnosing zygopophyseal joint pain. There are multiple studies evaluating the efficacy of lumbar facet thermal RF in the treatment of lumbar spondylosis. Gallagher and coworkers, in a double-blind, randomized, controlled trial, evaluated the efficacy of thermal RF compared with sham procedure. Follow-up at 1 and 6 months showed significantly better results in the thermal RF group.14 In 1999, Van Kleef and colleagues,15 in a doubleblind, randomized study of thermal RF lumbar facet denervation versus sham, observed a positive response in treated patients with a number needed-to-treat (NNT) of 1.6 at 12-month follow-up. Two years later, Leclaire and coworkers16 evaluated functional disability outcomes in 70 patients following thermal RF facet joint denervation. To diagnose the facet arthropathy, they performed intra-articular injections. Interestingly, positive responses were obtained from 70 of 76 patients screened (92% prevalence). Because the frequency of this pathology in patients with chronic lumbar pain is considerably below that level, the results of this study are questionable. In this study, the NNT was 11. The validity of a double-blind, randomized study by Van Wijk and coworkers17 has been questioned due to technical prob-
lems and concerns about whether the placebo group was or was not an active intervention. The NNT was 3.6. In a more recent study, Nath and coworkers performed a double-blind, randomized, controlled study in 40 patients.18 To confirm the diagnosis, they performed 3 medial branch diagnostic blocks. The patients were then randomized to a sham procedure versus thermal RF neurotomy. Evaluated outcomes included visual analog score (VAS), quality of life, and global perceived effect. At 6-month follow-up, strong improvement was seen in the active group. A recent systematic review by the ASIPP strongly supported the evidence for thermal RF facet joint neurotomy for short-term and longterm pain relief.19
Thermal radiofrequency of the dorsal root ganglion Encouraged by the positive results using thermal RF for the previously mentioned indications, the DRG became a target to treat patients with radicular symptoms. As described by Van Kleef, “The procedure is intended to expose the DRG to temperatures that prevail in the peripheral part of an RF lesion to preserve the large myelinated fibers and to deactivate the small myelinated fibers.”20 Several studies have been published, and the results have been mixed. Van Wijk and coworkers treated 270 patients prospectively with a diagnosis of lumbosacral pain. The median duration of pain relief was 44 weeks in 59% of the patients.21 They evaluated the efficacy of thermal RF of the lumbosacral DRG after selective nerve root block. In 1997, concerns about whether high temperature was a cause of poor outcome led Slappendel to compare the effects of thermal RF of the DRG in patients exposed to 40°C to those exposed to 67°C treatments.22 Patients were followed at 6 weeks and 3 months. Interestingly, although data revealed that neither group of patients obtained significant relief when compared with baseline, the concept that high temperature was unnecessary was born and led to the development of the PRF technique.
Sacroiliac joint pain Sacroiliac joint pain may affect up to 20% of patients with chronic low back pain. Cohen and coworkers23 performed a randomized, placebo-controlled study in 28 patients diagnosed with sacroiliac joint pain by intra-articular diagnostic injection. Fourteen patients received thermal RF denervation of the L4 medial branch, L5 posterior primary rami, and the lateral branches of S1, S2, and S3, whereas the other 14 patients underwent local anesthetic blocks and served as controls. Patients were followed at 1, 3, and 6 months postprocedure. Treatment success was considered when at least 50% pain relief was obtained. At 1-month follow-up, 79% of the active group had significant relief, and the benefit was maintained in 57% of patients at 6-month follow-up. Unfortunately, only 14% of the patients
Vallejo et al
RF vs. PRF
followed at 1 year postprocedure still experienced relief. Based on these preliminary results, sacroiliac denervation of the sacroiliac joint seems like a good option for patients refractory to other treatments.23
Pulsed radiofrequency In contrast with thermal RF, PRF is a nondestructive procedure, where electrical bursts of 20 msecond of electricity are applied followed by 480 msecond of no current to allow heat to dissipate, to keep the tissue temperature below 42°C. The concept behind it is that an electrical field spreading from the tip of the needle electrode will modulate nerve electrical conduction providing similar results to conventional thermal RF. Despite the popularity of this technique, there is little clinical evidence that strongly supports its use. In recent years, some animal studies have evaluated the potential mechanism of action of PRF. Cahana And coworkers, in an in vitro study, observed glial cell proliferation after hypocampus cells where exposed to PRF.24 Two different studies evaluated c-fos activation after PRF of the C6 DRG. It was interesting to observe that two different studies with similar methodologies observed different results. Yoshinori and colleagues25 observed c-fos activation in the dorsal horn with PRF but not thermal RF at 42°C, whereas Van Zundert observed similar effects in both groups.26 Recently, Hagiwara and coworkers27 elucidated the potential effect of PRF on the norepinephrine and serotonin systems after observing marked inhibition of the analgesic effect of PRF after the administration of specific neurotransmitter antagonists. Clinically, there are a large number of case reports and case series but few convincing randomized, controlled trials that support the use of PRF. Van Zundert and coworkers28 performed PRF of the trigeminal ganglion in 5 patients with pain refractory to conservative treatment. He followed them for 19 months and observed excellent pain relief in 3 patients, partial pain relief in 1, and no pain relief in the last patient.28 He even performed thermal RF on the nonresponsive patient, again with no success. The same group did PRF adjacent to the cervical DRG for patients with chronic cervical radicular pain in a double-blind, sham-controlled, randomized study.29 At 3 months and 6 months, they observed a statistical difference between the groups with improvements in global perception of effect and numeric rating and VAS with a trend toward improvement in quality of life in the PRF group.29 Since then, multiple case series have been published, suggesting a beneficial effect in conditions ranging from postherpetic neuralgia30,31 and sacroiliac joint pain32,33 to radicular low back pain.34 In a prospective case series, Vallejo and coworkers32 evaluated the efficacy of PRF in the treatment of sacroiliac joint pain by treating similar branches as the Cohen and coworkers series of patients treated with thermal RF. Twenty-two patients who had failed to respond to conservative treatment and intra-
131 articular steroid injections underwent PRF. Seventy-two percent of the patients reported 50% or better pain relief with a mean duration of the effect lasting 6-9 weeks in 4 patients, 10-16 weeks in 5 patients and 17-32 weeks 7 patients.32 Abejón and coworkers34 retrospectively evaluated the efficacy of PRF in patients with lumbar radicular pain. Prior to PRF, all patients had at least 50% pain relief with a single nerve root block. He then performed 75 PRFs in 54 patients. He observed significant improvement in global perception of effect in patients with herniated disks and spinal stenosis, whereas patients with failed back surgery syndrome did not achieve statistical improvement.34 Kim and coworkers31 performed PRF on the DRG on 49 patients with postherpetic neuralgia. Levels treated included 61% thoracic, 24% cervical, and 14% lumbar. At 12-week follow-up, the mean VAS dropped from 7.2 at baseline to 3.1.31
Comparative efficacy between conventional and thermal radiofrequency A prospective, randomized, double-blind study evaluated the efficacy of PRF versus thermal RF in patients with trigeminal neuralgia.35 Forty patients with similar demographics were randomized between the 2 groups. Evaluated outcomes included VAS, patient satisfaction scale, additional pharmacologic treatment, as well as side effects and complications. Only the thermal RF group achieved a statistically significant improvement in VAS and patient satisfaction scale. Only 2 of 20 patients in the PRF group had decreased VAS scores, but pain recurred in both of them at the 3-month follow-up. After 3 months, patients were allowed to crossover to thermal RF, and once again significant improvements were seen. The authors concluded that PRF is not an effective method of pain treatment for idiopathic trigeminal neuralgia.35 Two other comparative studies have assessed the benefit of these two techniques in patients with lumbar facet arthropathy.36,37 Tekin and coworkers,36 in a double-blind, randomized, controlled trial and following a single diagnostic block, randomized 60 patients between PRF, thermal RF, and local anesthetic injection. Patients were evaluated at 6 and 12 months. Only the thermal RF group showed a statistical benefit when compared with control.36 A similar study evaluated 50 patients and observed a decrease in VAS and improvement in disability that was statistically significant only in the thermal RF group. Follow-up was carried for only 3 months, and a major weakness of the study was a drop-out rate of 48% of patients.37
Conclusions Current evidence strongly supports thermal RF for the treatment of trigeminal neuralgia, cervical and lumbar facet spondylosis, and sacroiliac joint pain. Comparative efficacy
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studies have failed to support the use of PRF for the abovementioned indications. However, these comparative studies have often targeted those sites commonly addressed and proven efficacious by thermal RF. In contrast, PRF might prove more valuable in modulating nerve conduction in other pain syndromes, such as neuropathic pain conditions. As thermal RF, by definition, is contraindicated in neuropathic pain syndromes, it seems that the two techniques are essentially different and the indications for PRF still need to be defined.
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