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 1 *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. 213 214 Hata et al I. INTRODUCTION 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. II. HISTORICAL CONSIDERATIONS 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 Volume 23, Issue 1–4, 2011 Tekin et al.14 Erdine et al.13 Study 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 group. 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. Findings Randomized, double-blind, sham, lesion, controlled trial Study duration: 6 months RF, n = 20 Sample sizes: PRF, n = 20; Randomized, prospective, double-blind study Parameters 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. Conclusions Pulsed Radiofrequency Current in the Treatment of Pain 215 Simopoulos et al.16 Kroll et al.15 Study Sample sizes: PRF, n = 37; PRF + RF, n = 39 Randomized, prospective pilot study Study duration: 3 months PRF, n = 13 Sample sizes: RF, n = 13; Randomized, double-blinded trial Parameters 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 months. 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. Findings Conclusions 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 216 Hata et al Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 217 III. MECHANISM OF ACTION 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 Volume 23, Issue 1–4, 2011 218 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 Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 219 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. IV. BEHAVIORAL STUDIES 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 Volume 23, Issue 1–4, 2011 220 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 Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 221 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. Volume 23, Issue 1–4, 2011 222 Hata et al V. INDICATIONS 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 Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 223 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. Volume 23, Issue 1–4, 2011 224 Hata et al 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 Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 225 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. Volume 23, Issue 1–4, 2011 226 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 227 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. Volume 23, Issue 1–4, 2011 228 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 229 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. Volume 23, Issue 1–4, 2011 230 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 noted. Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 231 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 VI.DISCUSSION 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 Volume 23, Issue 1–4, 2011 Lumbar: 1 (1) Cervical: 1 (6) Facet pain Radicular 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) Neuralgia 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) Nonrandomized/Prospective Studies (n) Sacroiliac joint pain Trigeminal: 1 (17) RCTs (n) Etiology 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. Conclusions 232 Hata et al Critical Reviews™ in Physical and Rehabilitation Medicine Volume 23, Issue 1–4, 2011 Knee: 1 (36) Joint pain Hip: 1 (41) Shoulder: 4 (37–40) Atlantoaxial joint: 1 (36) Scaphoid/radial/lunate: 1 (36) Myofascial: 1 (35) Myofascial pain Nonrandomized/Prospective Studies (n) Lumbar: 1 (34) RCTs (n) Discogenic pain Etiology 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 Conclusions Pulsed Radiofrequency Current in the Treatment of Pain 233 234 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. REFERENCES 1. Ewert T, Limm H, Wessels T, Rackwitz B, von Garnier K, Freumuth R, Stucki G. The comparative effectiveness of a multimodal program versus exercise alone for the secondary prevention of chronic low back pain and disability. Phys Med. 2009;1:798–808. 2. van Boxem K, van Eerd M, Brinkuize T, Patijn J, van Kleef M, van Zundert J. Radiofrequency and pulsed radiofrequency radiofrequency treatment of chronic pain syndromes: the available evidence. Pain Pract. 2008;8:385–393. 3. Vallejo R, Benyamin RM, Kramer J, Stanton G, Joseph NJ. Pulsed radiofrequency denervation for the treatment of sacroiliac joint syndrome. Pain Med. 2006;7:429–434. 4. Orlandini G. Pulsed percutaneous radiofrequency treatment of the Gasserian ganglion for therapy of trigeminal neuralgia: technical notes, validity of the method and selection of the patients. Pain. 2004;108:297–298; author reply 298–299. 5. Navani A, Mahajan G, Kreis P, Fishman SM. A case of pulsed radiofrequency lesioning for occipital neuralgia. Pain Med. 2006;7:453–456. 6. Cohen SP, Sireci A, Wu CL, Larkin TM, Williams KA, Hurley RW. Pulsed radiofrequency of the dorsal root ganglia is superior to pharmacotherapy or pulsed radiofrequency of the intercostal nerves in the treatment of chronic postsurgical thoracic pain. Pain Physician. 2006;9:227–235. 7. Rhame EE, Levey KA, Gharibo CG. Successful treatment of refractory pudendal neuralgia with pulsed radiofrequency. Pain Physician. 2009;12:633–638. 8. Mitra R, Zeighami A, Mackey S. Pulsed radiofrequency for the treatment of chronic ilioinguinal neuropathy. Hernia. 2007;11:369–371. 9. Rozen D, Ahn J. Pulsed radiofrequency for the treatment of ilioinguinal neuralgia after inguinal herniorrhaphy. Mt Sinai J Med. 2006;73:716–718. Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 235 10.Shah RV, Racz GB. Pulsed mode radiofrequency lesioning to treat chronic post-tonsillectomy pain (secondary glossopharyngeal neuralgia). Pain Pract. 2003;3:232–237. 11.Tamimi MA, McCeney MH, Krutsch J. A case series of pulsed radiofrequency treatment of myofascial trigger points and scar neuromas. Pain Med. 2009;10:1140–1143. 12.Sluijter ME, Teixeira A, Serra V, Balogh S, Schianchi P. Intra-articular application of pulsed radiofrequency for arthrogenic pain–report of six cases. Pain Pract. 2008;8:57–61. 13.Erdine S, Ozyalcin NS, Cimen A, Celik M, Talu GK, Disci R. Comparison of pulsed radiofrequency with conventional radiofrequency in the treatment of idiopathic trigeminal neuralgia. Eur J Pain. 2007;11:309–313. 14.Tekin I, Mirzai H, Ok G, Erbuyun K, Vatansever D. A comparison of conventional and pulsed radiofrequency denervation in the treatment of chronic facet joint pain. Clin J Pain. 2007;23:524–529. 15.Kroll HR, Kim D, Danic MJ, Sankey SS, Gariwala M, Brown M. A randomized, double-blind, prospective study comparing the efficacy of continuous versus pulsed radiofrequency in the treatment of lumbar facet syndrome. J Clin Anesth. 2008;20:534–537. 16.Simopoulos TT, Kraemer J, Nagda JV, Aner M, Bajwa ZH. Response to pulsed and continuous radiofrequency lesioning of the dorsal root ganglion and segmental nerves in patients with chronic lumbar radicular pain. Pain Physician. 2008;11:137–144. 17.Sweet WH, Wepsic JG. Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers. 1. Trigeminal neuralgia. J Neurosurg. 1974;40:143–156. 18.Shealy CN. Percutaneous radiofrequency denervation of spinal facets. Treatment for chronic back pain and sciatica. J Neurosurg. 1975;43:448–451. 19.Uematsu S, Udvarhelyi GB, Benson DW, Siebens AA. Percutaneous radiofrequency rhizotomy. Surg Neurol. 1974;2:319–325. 20.Malik K, Benzon HT. Radiofrequency applications to dorsal root ganglia: a literature review. Anesthesiology. 2008;109:527–542. 21.Brodkey JS, Miyazaki Y, Ervin FR, Mark VH. Reversible heat lesions with radiofrequency current. A method of stereotactic localization. J Neurosurg. 1964;21:49–53. 22.Letcher FS, Goldring S. The effect of radiofrequency current and heat on peripheral nerve action potential in the cat. J Neurosurg. 1968;29:42–47. 23.Smith HP, McWhorter JM, Challa VR. Radiofrequency neurolysis in a clinical model. Neuropathological correlation. J Neurosurg. 1981;55:246–253. 24.Sluijter MC, ER Cosman, Rittman, WB, Van Kleef M. The effects of pulsed radiofrequency fields applied to the dorsal root ganglion. A preliminary report. The Pain Clinic 1998;11:109-17. 25.Bogduk N. Pulsed radiofrequency. Pain Med. 2006;7:396–407. Volume 23, Issue 1–4, 2011 236 Hata et al 26.Erdine S, Yucel A, Cimen A, Aydin S, Sav A, Bilir A. Effects of pulsed versus conventional radiofrequency current on rabbit dorsal root ganglion morpho logy. Eur J Pain. 2005;9:251–256. 27.Hamann W, Abou-Sherif S, Thompson S, Hall S. Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons. Eur J Pain. 2006;10:171–176. 28.Higuchi Y, Nashold BS Jr, Sluijter M, Cosman E, Pearlstein RD. Exposure of the dorsal root ganglion in rats to pulsed radiofrequency currents activates dorsal horn lamina I and II neurons. Neurosurgery. 2002;50:850–855; discussion 856. 29.Van Zundert J, de Louw AJ, Joosten EA, Kessels AG, Honig W, Dederen PJ, Veening JG, Vles JS, van Kleef M. Pulsed and continuous radiofrequency current adjacent to the cervical dorsal root ganglion of the rat induces late cellular activity in the dorsal horn. Anesthesiology. 2005;102:125–131. 30.Archer S, Li TT, Evans AT, Britland ST, Morgan H. Cell reactions to dielectrophoretic manipulation. Biochem Biophys Res Commun. 1999;257:687–698. 31.Sandkuhler J, Chen JG, Cheng G, Randic M. Low-frequency stimulation of afferent Adelta-fibers induces long-term depression at primary afferent synapses with substantia gelatinosa neurons in the rat. J Neurosci. 1997;17:6483–6491. 32.Cahana A, Vutskits L, Muller D. Acute differential modulation of synaptic transmission and cell survival during exposure to pulsed and continuous radiofrequency energy. J Pain 2003;4:197–202. 33.Pakhomov AG, Doyle J, Stuck BE, Murphy MR. Effects of high power microwave pulses on synaptic transmission and long term potentiation in hippocampus. Bioelectromagnetics 2003;24:174–181. 34.Hildebrandt J. [Relevance of nerve blocks in treating and diagnosing low back pain–is the quality decisive?] Schmerz. 2001;15:474–483. 35.Cosman ER Jr, Cosman ER Sr. Electric and thermal field effects in tissue around radiofrequency electrodes. Pain Med. 2005;6:405–424. 36.Richebe P, Rathmell JP, Brennan TJ. Immediate early genes after pulsed radiofrequency treatment: neurobiology in need of clinical trials. Anesthesiology. 2005;102:1–3. 37.Podhajsky RJ, Sekiguchi Y, Kikuchi S, Myers RR. The histologic effects of pulsed and continuous radiofrequency lesions at 42 degrees C to rat dorsal root ganglion and sciatic nerve. Spine (Phila Pa 1976). 2005;30:1008–1013. 38.Protasoni M, Reguzzoni M, Sangiorgi S, Reverberi C, Borsani E, Rodella LF, Dario A, Tomei G, Dell’Orbo C. Pulsed radiofrequency effects on the lumbar ganglion of the rat dorsal root: a morphological light and transmission electron microscopy study at acute stage. Eur Spine J. 2009;18:473–478. 39.Tun K, Cemil B, Gurcay AG, Kaptanoglu E, Sargon MF, Tekdemir I, Comert A, Kanpolat Y. Ultrastructural evaluation of pulsed radiofrequency and conventional radiofrequency lesions in rat sciatic nerve. Surg Neurol. 2009;72:496– 500, discussion 501. Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 237 40.Erdine S, Bilir A, Cosman ER, Cosman ER Jr. Ultrastructural changes in axons following exposure to pulsed radiofrequency fields. Pain Pract. 2009;9:407–417. 41.Chao SC, Lee HT, Kao TH, Yang MY, Tsuei YS, Shen CC, Tsou HK. Percutaneous pulsed radiofrequency in the treatment of cervical and lumbar radicular pain. Surg Neurol. 2008;70:59–65; discussion 65. 42.Hunter JC, Woodburn VL, Durieux C, Pettersson EK, Poat JA, Hughes J. c-fos Antisense oligodeoxynucleotide increases formalin-induced nociception and regulates preprodynorphin expression. Neuroscience. 1995;65:485–492. 43.Sandkuhler J, Treier AC, Liu XG, Ohnimus M. The massive expression of c-fos protein in spinal dorsal horn neurons is not followed by long-term changes in spinal nociception. Neuroscience. 1996;73:657–666. 44.Ozsoylar O, Akcali D, Cizmeci P, Babacan A, Cahana A, Bolay H. Percutaneous pulsed radiofrequency reduces mechanical allodynia in a neuropathic pain model. Anesth Analg. 2008;107:1406–1411. 45.Hagiwara S, Iwasaka H, Takeshima N, Noguchi T. Mechanisms of analgesic action of pulsed radiofrequency on adjuvant-induced pain in the rat: roles of descending adrenergic and serotonergic systems. Eur J Pain. 2009;13:249–252. 46.Aksu R, Ugur F, Bicer C, Menku A, Guler G, Madenoglu H, Canpolat DG, Boyaci A. The efficiency of pulsed radiofrequency application on L5 and L6 dorsal roots in rabbits developing neuropathic pain. Reg Anesth Pain Med. 2010;35:11–15. 47.Perret DM, Kim DS, Li KW, Sinavsky K, Newcomb RL, Miller JM, Luo ZD. Application of pulsed radiofrequency currents to rat dorsal root ganglia modulates nerve injury-induced tactile allodynia. Anesth Analg. 2011;113:610–616. 48.Abbott Z, Smuck M, Haig A, Sagher O. Irreversible spinal nerve injury from dorsal ramus radiofrequency neurotomy: a case report. Arch Phys Med Rehabil. 2007;88:1350–1352. 49.van Kleef M, Barendse GA, Kessels A, Voets HM, Weber WE, de Lange S. Randomized trial of radiofrequency lumbar facet denervation for chronic low back pain. Spine (Phila Pa 1976). 1999;24:1937–1942. 50.Dreyfuss P, Halbrook B, Pauza K, Joshi A, McLarty J, Bogduk N. Efficacy and validity of radiofrequency neurotomy for chronic lumbar zygapophysial joint pain. Spine (Phila Pa 1976). 2000;25:1270–1277. 51.Lord SM, Barnsley L, Wallis BJ, McDonald GJ, Bogduk N. Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med. 1996;335:1721–1726. 52.McDonald GJ, Lord SM, Bogduk N. Long-term follow-up of patients treated with cervical radiofrequency neurotomy for chronic neck pain. Neurosurgery. 1999;45:61–67; discussion 67–68. 53.Govind J, King W, Bailey B, Bogduk N. Radiofrequency neurotomy for the treatment of third occipital headache. J Neurol Neurosurg Psychiatry. 2003;74: 88–93. 54.Mikeladze G, Espinal R, Finnegan R, Routon J, Martin D. Pulsed radiofreVolume 23, Issue 1–4, 2011 238 Hata et al quency application in treatment of chronic zygapophyseal joint pain. Spine J. 2003;3:360–362. 55.Liliang PC, Lu K, Hsieh CH, Kao CY, Wang KW, Chen HJ. Pulsed radiofrequency of cervical medial branches for treatment of whiplash-related cervical zygapophysial joint pain. Surg Neurol. 2008;70(Suppl 1):S50–S55, discussion S55. 56.Lindner R, Sluijter ME, Schleinzer W. Pulsed radiofrequency treatment of the lumbar medial branch for facet pain: a retrospective analysis. Pain Med. 2006;7:435–439. 57.Sluijter ME, Koetsveld-Baart CC. Interruption of pain pathways in the treatment of the cervical syndrome. Anaesthesia. 1980;35:302–307. 58.Sluijter ME. Percutaneous facet denervation and partial posterior rhizotomy. Acta Anaesthesiol Belg. 1981;32:63–79. 59.Nash TP. Percutaneous radiofrequency lesioning of dorsal root ganglia for intractable pain. Pain. 1986;24:67–73. 60.Sluijter MM, M. Treatment of chronic pain in the back and neck by percutaneous thermal lesions. In: Miles JL, ed. Persistant Pain: Modern Methods of Treatment. London: Academic Press; 1981. p. 141–179. 61.Howe JF, Loeser JD, Calvin WH. Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression. Pain. 1977;3:25–41. 62.Smyth MW, Wright V. Sciatica and the intervertebral disc: an experimental study. J Bone Joint Surg Am. 1959;40A:1401–1418. 63.Abejon D, Ortego R, Solis R, Alaoui N, del Saz J, del Pozo C. Trans-facet-joint approach to pulsed radiofrequency ablation of the L5 dorsal root ganglion in a patient with degenerative spondylosis and scoliosis. Pain Pract. 2008;8:202–205. 64.Van Zundert J, Patijn J, Kessels A, Lame I, van Suijlekom H, van Kleef M. Pulsed radiofrequency adjacent to the cervical dorsal root ganglion in chronic cervical radicular pain: a double blind sham controlled randomized clinical trial. Pain. 2007;127:173–182. 65.Van Zundert J, LamÈ IE, de Louw A, Jansen J, Kessels F, Patijn J, van Kleef M. Percutaneous pulsed radiofrequency treatment of the cervical dorsal root ganglion in the treatment of chronic cervical pain syndromes: a clinical audit. Neuromodulation. 2003;6:6–14. 66.Pevzner E, David R, Leitner Y, Pekarsky I, Folman Y, Gepstein R. [Pulsed radiofrequency treatment of severe radicular pain]. Harefuah. 2005;144:178–180, 231. 67.Munglani R. The longer term effect of pulsed radiofrequency for neuropathic pain. Pain. 1999;80:437–439. 68.Teixeira A, Grandinson M, Sluijter ME. Pulsed radiofrequency for radicular pain due to a herniated intervertebral disc--an initial report. Pain Pract. 2005;5:111–115. Critical Reviews™ in Physical and Rehabilitation Medicine Pulsed Radiofrequency Current in the Treatment of Pain 239 69.Abejon D, Garcia-del-Valle S, Fuentes ML, Gomez-Arnau JI, Reig E, van Zundert J. Pulsed radiofrequency in lumbar radicular pain: clinical effects in various etiological groups. Pain Pract. 2007;7:21–26. 70.Van Zundert J, Brabant S, Van de Kelft E, Vercruyssen A, Van Buyten JP. Pulsed radiofrequency treatment of the Gasserian ganglion in patients with idiopathic trigeminal neuralgia. Pain. 2003;104:449–452. 71.Wildgaard K, Ravn J, Kehlet H. Chronic post-thoracotomy pain: a critical review of pathogenic mechanisms and strategies for prevention. Eur J Cardiothorac Surg. 2009;36:170–180. 72.Gerner P. Postthoracotomy pain management problems. Anesthesiol Clin. 2008;26:355–367, vii. 73.Steegers MA, Snik DM, Verhagen AF, van der Drift MA, Wilder-Smith OH. Only half of the chronic pain after thoracic surgery shows a neuropathic component. J Pain. 2008;9:955–961. 74.Shabat S, Pevsner Y, Folman Y, Gepstein R. Pulsed radiofrequency in the treatment of patients with chronic neuropathic spinal pain. Minim Invasive Neurosurg. 2006;49:147–149. 75.Haider N, Mekasha D, Chiravuri S, Wasserman R. Pulsed radiofrequency of the median nerve under ultrasound guidance. Pain Physician. 2007;10:765–770. 76.Ramanavarapu V, Simopoulos TT. Pulsed radiofrequency of lumbar dorsal root ganglia for chronic post-amputation stump pain. Pain Physician. 2008;11:561–566. 77.Shah RV, Racz GB. Long-term relief of posttraumatic headache by sphenopalatine ganglion pulsed radiofrequency lesioning: a case report. Arch Phys Med Rehabil. 2004;85:1013–1016. 78.Akkoc Y, Uyar M, Oncu J, Ozcan Z, Durmaz B. Complex regional pain syndrome in a patient with spinal cord injury: management with pulsed radiofrequency lumbar sympatholysis. Spinal Cord. 2008;46:82–84. 79.Teixeira A, Sluijter ME. Intradiscal high-voltage, long-duration pulsed radiofrequency for discogenic pain: a preliminary report. Pain Med. 2006;7:424–428. 80.Rohof OJ. Radiofrequency treatment of peripheral nerves. Pain Pract. 2002;2:257–260. 81.Shah RV, Racz GB. Pulsed mode radiofrequency lesioning of the suprascapular nerve for the treatment of chronic shoulder pain. Pain Physician. 2003;6: 503–506. 82.Liliang PC, Lu K, Liang CL, Tsai YD, Hsieh CH, Chen HJ. Pulsed radiofrequency lesioning of the suprascapular nerve for chronic shoulder pain: a preliminary report. Pain Med. 2009;10:70–75. 83.Kane TP, Rogers P, Hazelgrove J, Wimsey S, Harper GD. Pulsed radiofrequency applied to the suprascapular nerve in painful cuff tear arthropathy. J Shoulder Elbow Surg. 2008;17:436–440. 84.Kawaguchi M, Hashizume K, Iwata T, Furuya H. Percutaneous radiofrequency lesioning of sensory branches of the obturator and femoral nerves for the treatment of hip joint pain. Reg Anesth Pain Med. 2001;26:576–581. Volume 23, Issue 1–4, 2011 240 Hata et al 85.Malik A, Simopolous T, Elkersh M, Aner M, Bajwa ZH. Percutaneous radiofrequency lesioning of sensory branches of the obturator and femoral nerves for the treatment of non-operable hip pain. Pain Physician. 2003;6:499–502. 86.Wu H, Groner J. Pulsed radiofrequency treatment of articular branches of the obturator and femoral nerves for management of hip joint pain. Pain Pract. 2007;7:341–344. 87.Seref BS, Goktas S, Ergin A, Yildirim I, Atim A, Tahmaz L, Dayanc M. A novel treatment modality in patients with premature ejeculation resistant to conventional methods: the neuromodulation of dorsal penile nerves by pulsed radiofrequency. J Androl. 2010;31:126–130. 88.Frykberg R, Tierney E, Tallis A, Klotzbach T. Cell proliferation induction: healing chronic wounds through low-energy pulsed radiofrequency. Int J Low Extrem Wounds. 2009;8:45–51. 89.Porreca EG, Giordano-Jablon GM. Treatment of severe (stage III and IV) chronic pressure ulcers using pulsed radio frequency energy in a quadriplegic patient. Eplasty. 2008;8:e49. 90.Balogh SE. Transcutaneous application of pulsed radiofrequency: four case reports. Pain Pract. 2004;4:310–313. Critical Reviews™ in Physical and Rehabilitation Medicine
© Copyright 2024