ORIGINAL ARTICLE
Comparison of High-voltage- with Standardvoltage Pulsed Radiofrequency of Gasserian Ganglion in the Treatment of Idiopathic Trigeminal Neuralgia Luo Fang, MD*; Wang Tao, MD†; Lu Jingjing, MD‡; Ji Nan, MD† *Department of Anesthesiology and Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; †Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; ‡Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
& Abstract: Although pulsed radiofrequency treatment (PRFT) has been used to treat trigeminal neuralgia (TN) safely, satisfactory improvement is lacking. Recently, much attention has been paid to the PRFT dose and intra-operative parameters. It has been reported that high-voltage PRFT could significantly reduce discogenic pain. However, there is no study investigating the effects of high-voltage PRFT on TN. The aim of this prospective, randomized, double-blinded study was to evaluate the efficacy and safety of high-voltage PRFT in comparison with standard-voltage PRFT for idiopathic TN. Sixty severe TN patients were randomly assigned to 2 groups treated with CT-guided standard- or highvoltage-pulsed radiofrequency (RF) of Gasserian ganglion, respectively, between January 2012 and July 2012. Numeric Rating Scales (NRS), carbamazepine dose, and side effects were evaluated at day 1, weeks 1 and 2, months 1, 3, and 6, and 1 year postoperative. There were 27 patients in the standard-voltage group and 26 patients in the high-voltage group who completed the 1-year follow-up study. The effective rates in the standard-voltage and high-voltage
Address correspondence and reprint requests to: Ji Nan, MD, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. E-mail: [email protected]. Submitted: October 9, 2013; Revision accepted: April 15, 2014 DOI. 10.1111/papr.12227
© 2014 World Institute of Pain, 1530-7085/14/$15.00 Pain Practice, Volume 15, Issue 7, 2015 595–603
PRFT groups were 41% and 69%, respectively, at 1, 3, and 6 months postoperative (P = 0.037). The effective rate in the standard-voltage group decreased to 19% at 1-year postoperative, while in the high-voltage group remained at 69% (P = 0.000). No significant side effects were detected in both groups. In conclusion, CT-guided high-voltage PRFT is an effective and safe interventional therapeutic choice for idiopathic TN patients. & Key Words: trigeminal neuralgia, treatment, pulsed radiofrequency, Gasserian ganglion
INTRODUCTION Patients with severe trigeminal neuralgia (TN) who do not respond to conservative treatments are always subjected to interventional therapies or surgeries. Although interventional therapies such as balloon compression and radiofrequency (RF) thermocoagulation (RFTC) are safe and minimal invasive, they are neurodestructive and can cause related complications. Radiofrequency thermocoagulation is a continuous RF technology. Alternating current generated by a RF generator travels through the electrode into the tissues, causing ions in the tissue to move in the electric field, which heats the tissue and causes protein coagulation
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and degeneration, destroys nerves, and blocks pain signal transduction.1 Sluijter et al.2 described a novel kind of RF, namely pulsed RF. Alternating current (2 Hz impulse frequency, and 45 V output voltage) of 20-msecond duration and 480-msecond intervals is generated by a RF instrument.3 The heat caused by output voltage will dissipate during the interval, and the temperature of the electrode tip will not exceed 42°C and will not cause tissue degeneration.3 Pulsed radiofrequency treatment (PRFT) as a nondestructive technique is easily accepted by patients and clinicians because it treats neuropathic pain by “modulation” rather than blocking pain signal transduction.4–7 This treatment is safe and effective in treating various painful disorders.8,9 However, few studies have been conducted to investigate the effects of PRFT on TN. Van Zundert et al.10 firstly used PRFT to treat 5 patients with idiopathic TN. They suggested that PRFT was safe and suitable for aged or weak TN patients. In contrast, only 2 of 20 patients with TN experienced pain relief in a prospective, randomized, double-blind controlled study, and both of them suffered recurrence within 3 months.11 A number of reports indicated that PRFT efficacy in idiopathic TN was less than that observed with traditional RFTC.11–14 In 2013, Kim et al.15 also proposed that RFTC was more effective than PRFT for dental procedure-associated TN. Whether PRFT efficacy could be improved by increasing the PRFT dose and modifying intra-operative parameters has become an area of intense research. Teixeira and Sluijter suggested that PRFT with high intradiscal voltage (60 V) could significantly reduce discogenic pain severity.16 In our previous studies, we described how output voltage could be adjusted (from 27 to 50 V) according to target tissue resistance and specific anatomy characteristics when 42°C automatic pulsed RF mode of Baylis pain management RF generator was used; efficacy was positively correlated with output voltages during PRFT, suggesting that higher efficacy could be achieved by increasing the output voltage.17 However, to our knowledge, there are no studies investigating the effects of 42°C high-voltage PRFT obtained by manual mode of the RF generator on TN, which we did in the present study.
METHODS Patients We enrolled 60 consecutive patients from the Pain Management Center, Beijing Tiantan Hospital, with severe idiopathic TN who did not respond to conservative treatments between January 2012 and July 2012. The study was approved by the ethics committee of Beijing Tiantan Hospital, and all patients provided written informed consent. Patients were included if they meet the following criteria: > 18 years, without secondary TN induced by tumor and other disorders (defined by brain magnetic resonance imaging); with preoperative Numeric Rating Scales (NRS) score more than 7; and failure of oral carbamazepine or nerve blockade by steroid hormone to control pain. Patients were excluded if they met any of the following criteria: abnormal results of blood tests, hepatorenal function, blood glucose level, blood coagulation function, electrocardiogram (ECG) or chest X-ray examination, infection at the side of puncture, history of mental disorder, history of anesthesia drug abuse, previous treatment with invasive treatments, such as RFTC, balloon compression, destructive chemicals injection, gamma knife, peripheral neurotomy, or microvascular decompression (MVD). The 60 TN patients were randomly and equally assigned to standard-voltage group and high-voltage group treated with standard- or high-voltage PRFT, respectively. According to the sealed envelope defining the group of the patient, which was opened before the procedure, the choice of standard- or high-voltage PRFT was performed. Operation Continuous monitoring of blood pressure, heart rate, ECG, and pulse blood oxygen saturation were conducted while the patient was lying down on the CT scanner bed. The negative electrode of the pain management RF generator PMG-230 (Baylis Medical Inc., Montreal, QC, Canada) was placed on the skin of the patient’s upper back. After local infiltration anesthesia, the puncture was performed about 3 cm from the ipsilateral angulus oris. Thin-slice CT (SOMATOM; SIEMENS Company, Munich, Germany) scanning (2 mm/layer) and 3-D
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reconstruction-guided foramen ovale puncture were performed. We accurately punctured a 21-gauge, 10 cm RF treatment trocar with a 5 mm noninsulated tip (PMF-21-100-5; Baylis Medical Inc.) into the foramen ovale in accordance with the method described previously13 (Figure 1). The stylet was removed, the RF electrode (PMK-21100; Baylis Medical Inc.) was inserted, and electrical stimulation was conducted. Feeling threshold was determined by 50 Hz of electrical stimulation. Stimulation with 0.1 to 0.2 V of electrical stimulation could induce piercing pain in trigeminal nerve area. Motor threshold was determined by 2 Hz of electrical stimulation. Stimulation with 0.1 to 0.2 V of electrical stimulation could induce mandibular movement. The depth and direction of the needle was slightly adjusted according to patient’s feelings and movements to ensure puncture accuracy. For the patients in high-voltage group, manual pulse RF mode of RF generator was used with temperature no more than 42°C. The output voltage was gradually increased to reach the highest voltage for each patient (no obvious discomfort was reported, and every patient
Figure 1. Spiral CT-guided foramen ovale puncture. (A) Puncture localization. (B) 3-D reconstruction of the skull base showing that puncture direction is slightly deviated from foramen ovale (observed from external aspect). (C) 3-D reconstruction showing the needle (observed from external aspect) entering the foramen ovale. (D) 3-D reconstruction showing the needle (observed from internal aspect) in the foramen ovale.
could tolerate the treatment) for 240 seconds. The automatic pulsed RF mode of RF generator was used (42°C, 2 Hz) for 240 seconds in standard-voltage group. After 1 month, patients who did not respond underwent other treatments, such as conventional RFTC and so on. Pre-, intra-, and postoperative information were collected. For preoperative information, we collected age, sex, disease course, pain location (right/left side, involved branch), NRS, and carbamazepine doses. For intra-operative information, we collected the stimulating voltages used during electrical stimulation positioning with 50 and 2 Hz of electrical stimulation, surgery duration, output voltage, tissue resistance, and electric field intensity ([output voltage]2/resistance). For postoperative information, we collected NRS at day 1, weeks 1 and 2, months 1, 3, and 6, and 1-year postoperative, as well as carbamazepine doses and side effects. Numeric Rating Scales were used to evaluate pain severity, with 0 as the lowest score (no pain at all) and 10 as the highest score (most serious pain beyond endurance). Postoperative pain relief or NRS reduced by
A
B
C
D
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≥ 50% was considered effective. The effective rate was calculated by (numbers of patients who responded to the treatment/patients who completed the follow-up study) 9 100%. Statistical Analysis Statistical analysis was performed using SPSS 20.0 (SPSS Inc., Chicago, IL, USA). Normally distributed quantitative data are expressed as mean standard deviation (SD) and were analyzed with independent-samples t-tests, and quantitative data that are not normally distributed are expressed as median (range) and were analyzed with Mann–Whitney U-tests. Chi-square tests were employed to analyze qualitative data. P < 0.05 was considered statistically significant.
RESULTS Patients’ Demographics and Intra-operative Data Twenty-seven patients in the standard-voltage group and 26 patients in high-voltage group completed the 1year follow-up. The differences in baseline characteristics between the 2 groups were not significant (Table 1). No significant differences were detected between the 2 groups when comparing the stimulation positioning voltages of 50 or 2 Hz, tissue resistance, or surgery duration. The RF output voltage and electrical field intensity were significantly higher in the high-voltage group compared with the standard-voltage group (P = 0.000; Table 1). Treatment Effect Standard-voltage Group. A total of 11 (41%) patients had favorable outcome up to 6 months; 5 patients achieved total pain relief, and the dosage of carbamazepine was gradually decreased and eventually stopped; 6 patients achieved NRS relief > 50%, and their carbamazepine dose was gradually reduced. However, 6 of 11 patients suffered recurrence 7 to 11 months postoperation, and the effective rate at 1 year was only 19% (Table 2, Figure 2). Sixteen patients (59%) failed to respond to treatment 1-month postoperatively, and the carbamazepine dosage could not be decreased, so the patients underwent conventional RFTC treatment. All 16 patients achieved pain relief and did not require adjuvant medication after RFTC.
Table 1. Baseline operative Data
Patient No. Age (year) Male (%) Disease duration (year) Branches affected Maxillary nerve Mandibular nerve Maxillary & mandibular nerve Left-/right-sided Dosage of preoperative carbamazepine (mg/day) Preoperative NRS PRF output voltage (v) Electrical field intensity (W) Tissue resistance (Ω) 50 Hz stimulating voltage (v) 2 Hz stimulating voltage (v) Surgery duration (min)
Patient
Characteristics
and
Intra-
Standard-voltage Group
High-voltage Group
P Value
30 63.47 13.02 14 (46.7) 5.80 3.57
30 60.53 11.94 13 (43.3) 5.10 4.42
0.367 0.795 0.540
4 10 16
2 13 15
0.580
13/17 656.67 289.69
14/16 700.00 381.03
0.795 0.626
8 (7 to 10) 36.30 5.57
8 (7 to 10) 71.52 7.97
0.800 0.000
5.20 1.68
20.94 5.11
0.000
256.67 22.20
251.54 34.42
0.455
0.1 (0.1 to 0.2)
0.1 (0.1 to 0.2)
0.482
0.1 (0.1 to 0.2)
0.1 (0.1 to 0.2)
0.694
32.17 10.72
31.50 9.21
0.797
NRS, Numeric Rating Scales; PRF, pulsed radiofrequency.
High-voltage Group. Significant NRS decreases were found in 18 (69%) patients 1 year after high-voltage PRFT, and none of them suffered recurrence. Among these 18 patients, NRS was 0 in 13 patients, and they stopped the usage of carbamazepine; 5 patients achieved NRS relief > 50% and only required low doses of carbamazepine (100 to 300 mg/day) for pain control (Table 2, Figure 2). Eight patients (31%) failed to respond to treatment 1-month postoperatively; however, after conventional RFTC treatment in 7 patients and MVD treatment in 1 patient, NRS was reduced to 0 in all 8 patients, and they were able to stop taking carbamazepine. The effective rates of high-voltage group were higher than that of standard-voltage group 1 day, 1 and 2 weeks after surgery, but the differences were not statistically significant (P > 0.05). However, the effective rates of high-voltage group were significantly higher than that of standard-voltage group at 1-, 3-, and 6-months postoperation (P = 0.037), as well as 1-year postoperative (P = 0.000; Table 2). For the patients who responded to treatment, pain relief > 50% was found 1 day and 1 week after surgery
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Table 2. Effective Rates After Treatment (Intent-to-Treat Analysis) Standard-voltage Group (n = 30)
High-voltage Group (n = 30)
Time Point
NRS = 0
NRS Decrease > 50%
Effective Rate (%)
NRS = 0
NRS Decrease > 50%
Effective Rate (%)
P Value
1-day postoperation 1-week postoperation 2-weeks postoperation 1-month postoperation 3-months postoperation 6-months postoperation 1-year postoperation
0 0 4 5 5 5 4
13 15 10 9 9 9 4
43 50 47 47 47 47 27
4 3 6 14 14 14 14
12 14 12 8 8 8 8
53 57 60 73 73 73 73
0.438 0.605 0.301 0.035 0.035 0.035 0.018
NRS, Numeric Rating Scales.
in both groups. NRS continued to decrease in the highvoltage group at 2-weeks postoperative and remained stable at very low levels at 1, 3, 6 months, and 1 year without recurrence. The lowest NRS values in the standard-voltage group were found at 2-weeks and 1-month postoperative, but they were slightly increased at 3- and 6-months postoperation, and the differences at 3 and 6 months were significant between the 2 groups (P = 0.035, and 0.037, respectively). Several patients suffered recurrence and underwent secondary PRFT. After excluding these patients, only 5 (19%) patients in the standard-voltage group had achieved a good outcome (Table 3). We did not observe any serious complications related to PRFT. Side effects such as numbness or hypesthesia in trigeminal area were not reported by patients who only underwent PRFT. However, for patients who did not respond to PRFT and received RFTC treatment, hypesthesia in the trigeminal area and slight masticatory muscle weakness were found. One patient who underwent MVD treatment did not experienced complications associated with nerve destruction.
DISCUSSION In this study, manual pulsed RF mode of a RF generator was used to increase the output voltage during PRFT in the high-voltage group. The output voltages were determined on a case-by-case basis to ensure that every patient could tolerate the treatment. The temperature was set no more than 42°C to avoid nerve destruction. While in standard-voltage group, automatic pulsed RF mode proposed by former investigators was performed.10,11 The output voltages in the standard-voltage group were 36.37 5.44 V, and these values were increased by 97.69% (71.90 7.39 V) in the highvoltage group, suggesting that high-electric field PRFT was achieved in high-voltage group.
Overall, 69% of TN patients maintained satisfactory effects at the 6 months and 1 year postoperatively time point following high-voltage PRFT, which was much higher than that in the standard-voltage group at 6 months (41%) or 1 year (19%) and also higher than the results reported by Erdine et al.,11 who conducted PRFT with a 45-V output voltage for TN treatment using a different brand of RF generator. Among patients who responded to treatments, continuous NRS decrease was observed in the high-voltage group within 1 month and remained stable thereafter. For patients responded to standard-voltage PRFT, the lowest NRS values were observed 2-weeks and 1-month postoperation but increased at 3- and 6-months postoperatively. Six (55%) of 11 patients who responded to PRFT in the standard-voltage group experienced recurrence after 6 months and had to be treated again. The findings in this study suggest that high-voltage PRFT is more effective than standard-voltage PRFT. It could be a promising percutaneous intervention therapy for patients who do not respond to conservative treatments. Radiofrequency treatments include continuous RFTC and novel PRFT. The conventional RFTC treatment has been widely used for chronic pain treatment for more than 30 years. Thermal effects induced by high-frequency current can cause nerve tissue protein degeneration and block pain signal transduction. Although treating pain with RFTC is effective, it is a destructive treatment that controls symptoms but cannot remove the cause of pain. The destruction of trigeminal nerve will significantly decrease quality of life in TN patients. Pulsed RF treatment has only been used for about more than 10 years and can treat many kinds of painful disorders via a nonneurodestructive technique to modulate nerves.4–7,18 The rationale for using PRFT at the dorsal root ganglion in cervical radicular pain is at compelling,19 and PRFT has been shown to provide effective pain relief without severe adverse events for
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Figure 2. Flow chart and outcomes of the study. TN, trigeminal neuralgia; PRFT, pulsed radiofrequency treatment; MVD, microvascular decompression.
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Table 3. Comparison of NRS Over Time in Patients who Responded to Treatment Standard-voltage Group Time Point
Effective Numbers
Preoperation 1-day postoperation 1-week postoperation 2-weeks postoperation 1-month postoperation 3-months postoperation 6-months postoperation 1-year postoperation
13 15 14 14 11 11 5
High-voltage Group NRS
8 3 3 1 1 2 3 0
(7 (2 (1 (0 (0 (0 (0 (0
to to to to to to to to
Effective Numbers 10) 4) 4) 4) 3) 3) 4) 1)
16 17 18 21 18 18 18
P Value
NRS 8 (7 3 (0 3 (0 2 (0 0 (0 0 (0 0 (0 0 (0
to to to to to to to to
10) 4) 4) 4) 3) 3) 3) 3)
0.800 0.450 0.658 0.694 0.061 0.035 0.037 0.757
NRS, Numeric Rating Scales.
other pain disorders, such as lumbar facet joint pain,6 spinal disc pain,16 lumbosacral nerve root pain,9 and chronic headache8 etc. The advantages of PRFT make it a promising treatment for TN. However, several studies reported that although it did not cause obvious side effects, the treatment is not effective in treating TN.11–15 It was compelling that the 1-year effective rate of highvoltage PRFT for treating TN reached 69% in this study. In the present study, the preoperative characteristics and pain degree were similar between groups. All patients underwent accurate CT-guided puncture to target the trigeminal Gasserian ganglia reflected by the similar stimulating voltage using current of 50 or 2 Hz. No significant difference in tissue resistance was observed between the groups. The temperature was no more than 42°C. Therefore, the results indicated that it is the effects of high-electric fields rather than a thermal effect or other variables that can increase efficacy in the high-voltage group. The electric field of pulsed RF is mainly distributed at the tissues near the needle and diminishes rapidly about 0.1 to 0.2 mm away from needle tip,16 which necessitates accurate puncture. In recent years, we have achieved an effective rate of about 35% at 6-months postoperative when treating idiopathic TN by CTguided foramen ovale puncture and PRFT at Gasserian ganglion; the effective rate at 1 year is lower.13 We hypothesized that other methods besides accurate puncture should be performed to improve PRFT efficacy. Several animal experiments have been conducted to investigate the effects of different treatment durations,1,20 but the results are inconsistent. Two studies have hypothesized that electric fields, not thermal effect, can relieve pain during PRFT.4,21 Indeed, our recent study showed that the voltages received by patients differed from each other (27 to 50 V) during standard-voltage PRFT, and the voltages were higher in patients who responded to the treatment than in those
with poor therapeutic effects.17 Teixeira and Sluijter reported that 8 patients with discogenic pain who received high-voltage PRFT (60 V) achieved significant NRS decreases.16 According to a previously mentioned study, the results in this study verified that the efficacy of PRFT on TN patients improved significantly by increasing the pulsed output voltage. No obvious side effect was described while treating TN with PRFT in previous reports.10,11,13,17 Similarly, we did not observe any side effects in patients who underwent 42°C standard- and high-voltage PRFT. The results of the present study indicate that increased output voltage properly was fairly safe, suggesting that if the temperature is no more than 42°C, well-tolerated higher output voltage will not increase the risk of nerve tissue injury. A histopathological study demonstrated that PRFT with the temperature of 42°C could induce transient endoneurial edema of dorsal root ganglion and sciatic nerve, ultrastructure axon damage, abnormal morphological changes of mitochondria and membranes, collapse of microtubules and microfilaments, and myelin destruction in rats.22 However, no side effects were observed during clinical practice, suggesting that the benefits of the therapeutic effects of PRFT may outweigh the minor nerve tissue damage in patients. In the high-voltage group, the NRS continuously decreased within 1 month and reached the lowest value at 1-month postoperative. One month was needed to obtain the best therapeutic effects with high-voltage PRFT. This may be due to transient pathological changes induced by high-voltage PRFT, mild puncture injury, and modulation of PRFT working gradually. Clinicians should provide symptomatic treatment postoperatively within 1 month and inform the patients that it takes some time for the treatment to work. The findings of the present study suggest that, although high-voltage PRFT is more effective than standard-voltage PRFT without obvious side effects,
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the short-term effective rate (69%) is still lower than that of RFTC.23 Thus, the efficacy of high-voltage PRFT is still needed to be improved in the future. In this study, the patients who failed to respond to high-voltage PRFT achieved satisfied pain control effects after RFTC or MVD, suggesting that those who do not respond can still receive other kinds of invasive treatment without any residual effects. The exact mechanisms involving the pain relief effects of PRFT remain unclear. Changes in target tissues including early gene expression, stimulating descending inhibitory pathways, and inhibition of excitatory neurotransmission induced by electric field effects may be involved.24 Studies also suggest that pulsed electric fields could improve transmission, activate the immune system, and reduce chronic inflammatory reactions.25 However, further experimental studies are needed to clarify the exact mechanisms. There are several limitations of this study. We only reported the 1-year effective rate, and the long-term effects still need to be investigated. The efficacy of highvoltage PRFT in treating other kinds of neuropathic pain also needs to be elucidated. Further studies should be performed to investigate the correlation between output voltage and efficacy, to determine the most suitable output voltage, to identify the effects on target tissues, and to clarify the exact mechanisms. In summary, PRFT may modulate the nerves rather than destroy them. We believe it is a more promising method compared with neurodestructive treatments. High-voltage PRFT is as safe as standard-voltage PRFT and is more effective in treating idiopathic TN. Therefore, we suggest that clinicians use the well-tolerated high-voltage PRFT for TN patients. However, the ideal parameter is still deserved to be determined.
REFERENCES 1. Ozsoylar O, Akcßali 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. 2. Sluijter ME, Cosman E, Rittman W, van Kleef M. The effect of pulsed radiofrequency fields applied to the dorsal root ganglion – a preliminary report. Pain Clin. 1998;11:109–117. 3. Snidvongs S, Mehta V. Pulsed radiofrequency: a nonneurodestructive therapy in pain management. Curr Opin Support Palliat Care. 2010;4:107–110. 4. Cahana A, Zundert J, Macrea L, Kleef M, Sluijter M. Pulsed radiofrequency: current clinical and biological literature available. Pain Med. 2006;7:411–423.
5. Kang KN, Park IK, Suh JH, Leem JG, Shin JW. Ultrasound-guided Pulsed Radiofrequency Lesioning of the Phrenic Nerve in a Patient with Intractable Hiccup. Korean J Pain. 2010;23:198–201. 6. 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. 7. Rehman SU, Khan MZ, Hussain R, Jamshed A. Pulsed radiofrequency modulation for lingual neuralgia. Br J Oral Maxillofac Surg. 2012;50:e4–e5. 8. Shabat S, Leitner J, Folman Y. Pulsed radiofrequency for the suprascapular nerve for patients with chronic headache. J Neurosurg Anesthesiol. 2013;25:340–343. 9. Van Boxem K, van Bilsen J, de Meij N, et al. Pulsed radiofrequency treatment adjacent to the lumbar dorsal root ganglion for the management of lumbosacral radicular syndrome: a clinical audit. Pain Med. 2011;12:1322–1330. 10. 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. 11. 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. 12. Chua NH, Vissers KC, Sluijter ME. Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications—a review. Acta Neurochir (Wien). 2011;153:763–771. 13. Luo F, Shen Y, Wang T, Meng L, Yu X, Ji N. 3D CTGuided pulsed radiofrequency treatment for trigeminal neuralgia. Pain Pract. 2014;14:16–21. 14. van Boxem K, van Eerd M, Brinkhuizen T, Patijn J, van Kleef M, van Zundert J. Radiofrequency and pulsed radiofrequency treatment of chronic pain syndromes: the available evidence. Pain Pract. 2008;8:385–393. 15. Kim JH, Yu HY, Park SY, Lee SC, Kim YC. Pulsed and conventional radiofrequency treatment: which is effective for dental procedure-related symptomatic trigeminal neuralgia? Pain Med. 2013;14:430–435. 16. Teixeira A, Sluijter ME. Intradiscal high-voltage, longduration pulsed radiofrequency for discogenic pain: a preliminary report. Pain Med. 2006;7:424–428. 17. Luo F, Meng L, Wang T, Yu X, Shen Y, Ji N. Pulsed radiofrequency treatment for idiopathic trigeminal neuralgia: a retrospective analysis of the causes for ineffective pain relief. Eur J Pain. 2013;17:1189–1192. 18. Cohen SP, Zundert J. Pulsed radiofrequency: rebel without cause. Reg Anesth Pain Med. 2010;35:8–10. 19. 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.
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20. Tanaka N, Yamaga M, Tateyama S, Uno T, Tsuneyoshi I, Takasaki M. The effect of pulsed radiofrequency current on mechanical allodynia induced with resiniferatoxin in rats. Anesth Analg. 2010;111:784–790. 21. 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. 22. 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.
23. Son BC, Kim HS, Kim IS, Yang SH, Lee SW. Percutaneous radiofrequency thermocoagulation under fluoroscopic image-guidance for idiopathic trigeminal neuralgia. J Korean Neurosurg Soc. 2011;50:446–452. 24. Todorov L. Pulsed radiofrequency of the sural nerve for the treatment of chronic ankle pain. Pain Physician. 2011;14:301–304. 25. Rohof O. Intradiscal pulsed radiofrequency application following provocative discography for the management of degenerative disc disease and concordant pain: a pilot study. Pain Pract. 2012;12:342–349.
Comparison of High-voltage- with Standardvoltage Pulsed Radiofrequency of Gasserian Ganglion in the Treatment of Idiopathic Trigeminal Neuralgia Luo Fang, MD*; Wang Tao, MD†; Lu Jingjing, MD‡; Ji Nan, MD† *Department of Anesthesiology and Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; †Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; ‡Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
& Abstract: Although pulsed radiofrequency treatment (PRFT) has been used to treat trigeminal neuralgia (TN) safely, satisfactory improvement is lacking. Recently, much attention has been paid to the PRFT dose and intra-operative parameters. It has been reported that high-voltage PRFT could significantly reduce discogenic pain. However, there is no study investigating the effects of high-voltage PRFT on TN. The aim of this prospective, randomized, double-blinded study was to evaluate the efficacy and safety of high-voltage PRFT in comparison with standard-voltage PRFT for idiopathic TN. Sixty severe TN patients were randomly assigned to 2 groups treated with CT-guided standard- or highvoltage-pulsed radiofrequency (RF) of Gasserian ganglion, respectively, between January 2012 and July 2012. Numeric Rating Scales (NRS), carbamazepine dose, and side effects were evaluated at day 1, weeks 1 and 2, months 1, 3, and 6, and 1 year postoperative. There were 27 patients in the standard-voltage group and 26 patients in the high-voltage group who completed the 1-year follow-up study. The effective rates in the standard-voltage and high-voltage
Address correspondence and reprint requests to: Ji Nan, MD, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. E-mail: [email protected]. Submitted: October 9, 2013; Revision accepted: April 15, 2014 DOI. 10.1111/papr.12227
© 2014 World Institute of Pain, 1530-7085/14/$15.00 Pain Practice, Volume 15, Issue 7, 2015 595–603
PRFT groups were 41% and 69%, respectively, at 1, 3, and 6 months postoperative (P = 0.037). The effective rate in the standard-voltage group decreased to 19% at 1-year postoperative, while in the high-voltage group remained at 69% (P = 0.000). No significant side effects were detected in both groups. In conclusion, CT-guided high-voltage PRFT is an effective and safe interventional therapeutic choice for idiopathic TN patients. & Key Words: trigeminal neuralgia, treatment, pulsed radiofrequency, Gasserian ganglion
INTRODUCTION Patients with severe trigeminal neuralgia (TN) who do not respond to conservative treatments are always subjected to interventional therapies or surgeries. Although interventional therapies such as balloon compression and radiofrequency (RF) thermocoagulation (RFTC) are safe and minimal invasive, they are neurodestructive and can cause related complications. Radiofrequency thermocoagulation is a continuous RF technology. Alternating current generated by a RF generator travels through the electrode into the tissues, causing ions in the tissue to move in the electric field, which heats the tissue and causes protein coagulation
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and degeneration, destroys nerves, and blocks pain signal transduction.1 Sluijter et al.2 described a novel kind of RF, namely pulsed RF. Alternating current (2 Hz impulse frequency, and 45 V output voltage) of 20-msecond duration and 480-msecond intervals is generated by a RF instrument.3 The heat caused by output voltage will dissipate during the interval, and the temperature of the electrode tip will not exceed 42°C and will not cause tissue degeneration.3 Pulsed radiofrequency treatment (PRFT) as a nondestructive technique is easily accepted by patients and clinicians because it treats neuropathic pain by “modulation” rather than blocking pain signal transduction.4–7 This treatment is safe and effective in treating various painful disorders.8,9 However, few studies have been conducted to investigate the effects of PRFT on TN. Van Zundert et al.10 firstly used PRFT to treat 5 patients with idiopathic TN. They suggested that PRFT was safe and suitable for aged or weak TN patients. In contrast, only 2 of 20 patients with TN experienced pain relief in a prospective, randomized, double-blind controlled study, and both of them suffered recurrence within 3 months.11 A number of reports indicated that PRFT efficacy in idiopathic TN was less than that observed with traditional RFTC.11–14 In 2013, Kim et al.15 also proposed that RFTC was more effective than PRFT for dental procedure-associated TN. Whether PRFT efficacy could be improved by increasing the PRFT dose and modifying intra-operative parameters has become an area of intense research. Teixeira and Sluijter suggested that PRFT with high intradiscal voltage (60 V) could significantly reduce discogenic pain severity.16 In our previous studies, we described how output voltage could be adjusted (from 27 to 50 V) according to target tissue resistance and specific anatomy characteristics when 42°C automatic pulsed RF mode of Baylis pain management RF generator was used; efficacy was positively correlated with output voltages during PRFT, suggesting that higher efficacy could be achieved by increasing the output voltage.17 However, to our knowledge, there are no studies investigating the effects of 42°C high-voltage PRFT obtained by manual mode of the RF generator on TN, which we did in the present study.
METHODS Patients We enrolled 60 consecutive patients from the Pain Management Center, Beijing Tiantan Hospital, with severe idiopathic TN who did not respond to conservative treatments between January 2012 and July 2012. The study was approved by the ethics committee of Beijing Tiantan Hospital, and all patients provided written informed consent. Patients were included if they meet the following criteria: > 18 years, without secondary TN induced by tumor and other disorders (defined by brain magnetic resonance imaging); with preoperative Numeric Rating Scales (NRS) score more than 7; and failure of oral carbamazepine or nerve blockade by steroid hormone to control pain. Patients were excluded if they met any of the following criteria: abnormal results of blood tests, hepatorenal function, blood glucose level, blood coagulation function, electrocardiogram (ECG) or chest X-ray examination, infection at the side of puncture, history of mental disorder, history of anesthesia drug abuse, previous treatment with invasive treatments, such as RFTC, balloon compression, destructive chemicals injection, gamma knife, peripheral neurotomy, or microvascular decompression (MVD). The 60 TN patients were randomly and equally assigned to standard-voltage group and high-voltage group treated with standard- or high-voltage PRFT, respectively. According to the sealed envelope defining the group of the patient, which was opened before the procedure, the choice of standard- or high-voltage PRFT was performed. Operation Continuous monitoring of blood pressure, heart rate, ECG, and pulse blood oxygen saturation were conducted while the patient was lying down on the CT scanner bed. The negative electrode of the pain management RF generator PMG-230 (Baylis Medical Inc., Montreal, QC, Canada) was placed on the skin of the patient’s upper back. After local infiltration anesthesia, the puncture was performed about 3 cm from the ipsilateral angulus oris. Thin-slice CT (SOMATOM; SIEMENS Company, Munich, Germany) scanning (2 mm/layer) and 3-D
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reconstruction-guided foramen ovale puncture were performed. We accurately punctured a 21-gauge, 10 cm RF treatment trocar with a 5 mm noninsulated tip (PMF-21-100-5; Baylis Medical Inc.) into the foramen ovale in accordance with the method described previously13 (Figure 1). The stylet was removed, the RF electrode (PMK-21100; Baylis Medical Inc.) was inserted, and electrical stimulation was conducted. Feeling threshold was determined by 50 Hz of electrical stimulation. Stimulation with 0.1 to 0.2 V of electrical stimulation could induce piercing pain in trigeminal nerve area. Motor threshold was determined by 2 Hz of electrical stimulation. Stimulation with 0.1 to 0.2 V of electrical stimulation could induce mandibular movement. The depth and direction of the needle was slightly adjusted according to patient’s feelings and movements to ensure puncture accuracy. For the patients in high-voltage group, manual pulse RF mode of RF generator was used with temperature no more than 42°C. The output voltage was gradually increased to reach the highest voltage for each patient (no obvious discomfort was reported, and every patient
Figure 1. Spiral CT-guided foramen ovale puncture. (A) Puncture localization. (B) 3-D reconstruction of the skull base showing that puncture direction is slightly deviated from foramen ovale (observed from external aspect). (C) 3-D reconstruction showing the needle (observed from external aspect) entering the foramen ovale. (D) 3-D reconstruction showing the needle (observed from internal aspect) in the foramen ovale.
could tolerate the treatment) for 240 seconds. The automatic pulsed RF mode of RF generator was used (42°C, 2 Hz) for 240 seconds in standard-voltage group. After 1 month, patients who did not respond underwent other treatments, such as conventional RFTC and so on. Pre-, intra-, and postoperative information were collected. For preoperative information, we collected age, sex, disease course, pain location (right/left side, involved branch), NRS, and carbamazepine doses. For intra-operative information, we collected the stimulating voltages used during electrical stimulation positioning with 50 and 2 Hz of electrical stimulation, surgery duration, output voltage, tissue resistance, and electric field intensity ([output voltage]2/resistance). For postoperative information, we collected NRS at day 1, weeks 1 and 2, months 1, 3, and 6, and 1-year postoperative, as well as carbamazepine doses and side effects. Numeric Rating Scales were used to evaluate pain severity, with 0 as the lowest score (no pain at all) and 10 as the highest score (most serious pain beyond endurance). Postoperative pain relief or NRS reduced by
A
B
C
D
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≥ 50% was considered effective. The effective rate was calculated by (numbers of patients who responded to the treatment/patients who completed the follow-up study) 9 100%. Statistical Analysis Statistical analysis was performed using SPSS 20.0 (SPSS Inc., Chicago, IL, USA). Normally distributed quantitative data are expressed as mean standard deviation (SD) and were analyzed with independent-samples t-tests, and quantitative data that are not normally distributed are expressed as median (range) and were analyzed with Mann–Whitney U-tests. Chi-square tests were employed to analyze qualitative data. P < 0.05 was considered statistically significant.
RESULTS Patients’ Demographics and Intra-operative Data Twenty-seven patients in the standard-voltage group and 26 patients in high-voltage group completed the 1year follow-up. The differences in baseline characteristics between the 2 groups were not significant (Table 1). No significant differences were detected between the 2 groups when comparing the stimulation positioning voltages of 50 or 2 Hz, tissue resistance, or surgery duration. The RF output voltage and electrical field intensity were significantly higher in the high-voltage group compared with the standard-voltage group (P = 0.000; Table 1). Treatment Effect Standard-voltage Group. A total of 11 (41%) patients had favorable outcome up to 6 months; 5 patients achieved total pain relief, and the dosage of carbamazepine was gradually decreased and eventually stopped; 6 patients achieved NRS relief > 50%, and their carbamazepine dose was gradually reduced. However, 6 of 11 patients suffered recurrence 7 to 11 months postoperation, and the effective rate at 1 year was only 19% (Table 2, Figure 2). Sixteen patients (59%) failed to respond to treatment 1-month postoperatively, and the carbamazepine dosage could not be decreased, so the patients underwent conventional RFTC treatment. All 16 patients achieved pain relief and did not require adjuvant medication after RFTC.
Table 1. Baseline operative Data
Patient No. Age (year) Male (%) Disease duration (year) Branches affected Maxillary nerve Mandibular nerve Maxillary & mandibular nerve Left-/right-sided Dosage of preoperative carbamazepine (mg/day) Preoperative NRS PRF output voltage (v) Electrical field intensity (W) Tissue resistance (Ω) 50 Hz stimulating voltage (v) 2 Hz stimulating voltage (v) Surgery duration (min)
Patient
Characteristics
and
Intra-
Standard-voltage Group
High-voltage Group
P Value
30 63.47 13.02 14 (46.7) 5.80 3.57
30 60.53 11.94 13 (43.3) 5.10 4.42
0.367 0.795 0.540
4 10 16
2 13 15
0.580
13/17 656.67 289.69
14/16 700.00 381.03
0.795 0.626
8 (7 to 10) 36.30 5.57
8 (7 to 10) 71.52 7.97
0.800 0.000
5.20 1.68
20.94 5.11
0.000
256.67 22.20
251.54 34.42
0.455
0.1 (0.1 to 0.2)
0.1 (0.1 to 0.2)
0.482
0.1 (0.1 to 0.2)
0.1 (0.1 to 0.2)
0.694
32.17 10.72
31.50 9.21
0.797
NRS, Numeric Rating Scales; PRF, pulsed radiofrequency.
High-voltage Group. Significant NRS decreases were found in 18 (69%) patients 1 year after high-voltage PRFT, and none of them suffered recurrence. Among these 18 patients, NRS was 0 in 13 patients, and they stopped the usage of carbamazepine; 5 patients achieved NRS relief > 50% and only required low doses of carbamazepine (100 to 300 mg/day) for pain control (Table 2, Figure 2). Eight patients (31%) failed to respond to treatment 1-month postoperatively; however, after conventional RFTC treatment in 7 patients and MVD treatment in 1 patient, NRS was reduced to 0 in all 8 patients, and they were able to stop taking carbamazepine. The effective rates of high-voltage group were higher than that of standard-voltage group 1 day, 1 and 2 weeks after surgery, but the differences were not statistically significant (P > 0.05). However, the effective rates of high-voltage group were significantly higher than that of standard-voltage group at 1-, 3-, and 6-months postoperation (P = 0.037), as well as 1-year postoperative (P = 0.000; Table 2). For the patients who responded to treatment, pain relief > 50% was found 1 day and 1 week after surgery
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Table 2. Effective Rates After Treatment (Intent-to-Treat Analysis) Standard-voltage Group (n = 30)
High-voltage Group (n = 30)
Time Point
NRS = 0
NRS Decrease > 50%
Effective Rate (%)
NRS = 0
NRS Decrease > 50%
Effective Rate (%)
P Value
1-day postoperation 1-week postoperation 2-weeks postoperation 1-month postoperation 3-months postoperation 6-months postoperation 1-year postoperation
0 0 4 5 5 5 4
13 15 10 9 9 9 4
43 50 47 47 47 47 27
4 3 6 14 14 14 14
12 14 12 8 8 8 8
53 57 60 73 73 73 73
0.438 0.605 0.301 0.035 0.035 0.035 0.018
NRS, Numeric Rating Scales.
in both groups. NRS continued to decrease in the highvoltage group at 2-weeks postoperative and remained stable at very low levels at 1, 3, 6 months, and 1 year without recurrence. The lowest NRS values in the standard-voltage group were found at 2-weeks and 1-month postoperative, but they were slightly increased at 3- and 6-months postoperation, and the differences at 3 and 6 months were significant between the 2 groups (P = 0.035, and 0.037, respectively). Several patients suffered recurrence and underwent secondary PRFT. After excluding these patients, only 5 (19%) patients in the standard-voltage group had achieved a good outcome (Table 3). We did not observe any serious complications related to PRFT. Side effects such as numbness or hypesthesia in trigeminal area were not reported by patients who only underwent PRFT. However, for patients who did not respond to PRFT and received RFTC treatment, hypesthesia in the trigeminal area and slight masticatory muscle weakness were found. One patient who underwent MVD treatment did not experienced complications associated with nerve destruction.
DISCUSSION In this study, manual pulsed RF mode of a RF generator was used to increase the output voltage during PRFT in the high-voltage group. The output voltages were determined on a case-by-case basis to ensure that every patient could tolerate the treatment. The temperature was set no more than 42°C to avoid nerve destruction. While in standard-voltage group, automatic pulsed RF mode proposed by former investigators was performed.10,11 The output voltages in the standard-voltage group were 36.37 5.44 V, and these values were increased by 97.69% (71.90 7.39 V) in the highvoltage group, suggesting that high-electric field PRFT was achieved in high-voltage group.
Overall, 69% of TN patients maintained satisfactory effects at the 6 months and 1 year postoperatively time point following high-voltage PRFT, which was much higher than that in the standard-voltage group at 6 months (41%) or 1 year (19%) and also higher than the results reported by Erdine et al.,11 who conducted PRFT with a 45-V output voltage for TN treatment using a different brand of RF generator. Among patients who responded to treatments, continuous NRS decrease was observed in the high-voltage group within 1 month and remained stable thereafter. For patients responded to standard-voltage PRFT, the lowest NRS values were observed 2-weeks and 1-month postoperation but increased at 3- and 6-months postoperatively. Six (55%) of 11 patients who responded to PRFT in the standard-voltage group experienced recurrence after 6 months and had to be treated again. The findings in this study suggest that high-voltage PRFT is more effective than standard-voltage PRFT. It could be a promising percutaneous intervention therapy for patients who do not respond to conservative treatments. Radiofrequency treatments include continuous RFTC and novel PRFT. The conventional RFTC treatment has been widely used for chronic pain treatment for more than 30 years. Thermal effects induced by high-frequency current can cause nerve tissue protein degeneration and block pain signal transduction. Although treating pain with RFTC is effective, it is a destructive treatment that controls symptoms but cannot remove the cause of pain. The destruction of trigeminal nerve will significantly decrease quality of life in TN patients. Pulsed RF treatment has only been used for about more than 10 years and can treat many kinds of painful disorders via a nonneurodestructive technique to modulate nerves.4–7,18 The rationale for using PRFT at the dorsal root ganglion in cervical radicular pain is at compelling,19 and PRFT has been shown to provide effective pain relief without severe adverse events for
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Figure 2. Flow chart and outcomes of the study. TN, trigeminal neuralgia; PRFT, pulsed radiofrequency treatment; MVD, microvascular decompression.
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Table 3. Comparison of NRS Over Time in Patients who Responded to Treatment Standard-voltage Group Time Point
Effective Numbers
Preoperation 1-day postoperation 1-week postoperation 2-weeks postoperation 1-month postoperation 3-months postoperation 6-months postoperation 1-year postoperation
13 15 14 14 11 11 5
High-voltage Group NRS
8 3 3 1 1 2 3 0
(7 (2 (1 (0 (0 (0 (0 (0
to to to to to to to to
Effective Numbers 10) 4) 4) 4) 3) 3) 4) 1)
16 17 18 21 18 18 18
P Value
NRS 8 (7 3 (0 3 (0 2 (0 0 (0 0 (0 0 (0 0 (0
to to to to to to to to
10) 4) 4) 4) 3) 3) 3) 3)
0.800 0.450 0.658 0.694 0.061 0.035 0.037 0.757
NRS, Numeric Rating Scales.
other pain disorders, such as lumbar facet joint pain,6 spinal disc pain,16 lumbosacral nerve root pain,9 and chronic headache8 etc. The advantages of PRFT make it a promising treatment for TN. However, several studies reported that although it did not cause obvious side effects, the treatment is not effective in treating TN.11–15 It was compelling that the 1-year effective rate of highvoltage PRFT for treating TN reached 69% in this study. In the present study, the preoperative characteristics and pain degree were similar between groups. All patients underwent accurate CT-guided puncture to target the trigeminal Gasserian ganglia reflected by the similar stimulating voltage using current of 50 or 2 Hz. No significant difference in tissue resistance was observed between the groups. The temperature was no more than 42°C. Therefore, the results indicated that it is the effects of high-electric fields rather than a thermal effect or other variables that can increase efficacy in the high-voltage group. The electric field of pulsed RF is mainly distributed at the tissues near the needle and diminishes rapidly about 0.1 to 0.2 mm away from needle tip,16 which necessitates accurate puncture. In recent years, we have achieved an effective rate of about 35% at 6-months postoperative when treating idiopathic TN by CTguided foramen ovale puncture and PRFT at Gasserian ganglion; the effective rate at 1 year is lower.13 We hypothesized that other methods besides accurate puncture should be performed to improve PRFT efficacy. Several animal experiments have been conducted to investigate the effects of different treatment durations,1,20 but the results are inconsistent. Two studies have hypothesized that electric fields, not thermal effect, can relieve pain during PRFT.4,21 Indeed, our recent study showed that the voltages received by patients differed from each other (27 to 50 V) during standard-voltage PRFT, and the voltages were higher in patients who responded to the treatment than in those
with poor therapeutic effects.17 Teixeira and Sluijter reported that 8 patients with discogenic pain who received high-voltage PRFT (60 V) achieved significant NRS decreases.16 According to a previously mentioned study, the results in this study verified that the efficacy of PRFT on TN patients improved significantly by increasing the pulsed output voltage. No obvious side effect was described while treating TN with PRFT in previous reports.10,11,13,17 Similarly, we did not observe any side effects in patients who underwent 42°C standard- and high-voltage PRFT. The results of the present study indicate that increased output voltage properly was fairly safe, suggesting that if the temperature is no more than 42°C, well-tolerated higher output voltage will not increase the risk of nerve tissue injury. A histopathological study demonstrated that PRFT with the temperature of 42°C could induce transient endoneurial edema of dorsal root ganglion and sciatic nerve, ultrastructure axon damage, abnormal morphological changes of mitochondria and membranes, collapse of microtubules and microfilaments, and myelin destruction in rats.22 However, no side effects were observed during clinical practice, suggesting that the benefits of the therapeutic effects of PRFT may outweigh the minor nerve tissue damage in patients. In the high-voltage group, the NRS continuously decreased within 1 month and reached the lowest value at 1-month postoperative. One month was needed to obtain the best therapeutic effects with high-voltage PRFT. This may be due to transient pathological changes induced by high-voltage PRFT, mild puncture injury, and modulation of PRFT working gradually. Clinicians should provide symptomatic treatment postoperatively within 1 month and inform the patients that it takes some time for the treatment to work. The findings of the present study suggest that, although high-voltage PRFT is more effective than standard-voltage PRFT without obvious side effects,
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the short-term effective rate (69%) is still lower than that of RFTC.23 Thus, the efficacy of high-voltage PRFT is still needed to be improved in the future. In this study, the patients who failed to respond to high-voltage PRFT achieved satisfied pain control effects after RFTC or MVD, suggesting that those who do not respond can still receive other kinds of invasive treatment without any residual effects. The exact mechanisms involving the pain relief effects of PRFT remain unclear. Changes in target tissues including early gene expression, stimulating descending inhibitory pathways, and inhibition of excitatory neurotransmission induced by electric field effects may be involved.24 Studies also suggest that pulsed electric fields could improve transmission, activate the immune system, and reduce chronic inflammatory reactions.25 However, further experimental studies are needed to clarify the exact mechanisms. There are several limitations of this study. We only reported the 1-year effective rate, and the long-term effects still need to be investigated. The efficacy of highvoltage PRFT in treating other kinds of neuropathic pain also needs to be elucidated. Further studies should be performed to investigate the correlation between output voltage and efficacy, to determine the most suitable output voltage, to identify the effects on target tissues, and to clarify the exact mechanisms. In summary, PRFT may modulate the nerves rather than destroy them. We believe it is a more promising method compared with neurodestructive treatments. High-voltage PRFT is as safe as standard-voltage PRFT and is more effective in treating idiopathic TN. Therefore, we suggest that clinicians use the well-tolerated high-voltage PRFT for TN patients. However, the ideal parameter is still deserved to be determined.
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5. Kang KN, Park IK, Suh JH, Leem JG, Shin JW. Ultrasound-guided Pulsed Radiofrequency Lesioning of the Phrenic Nerve in a Patient with Intractable Hiccup. Korean J Pain. 2010;23:198–201. 6. 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. 7. Rehman SU, Khan MZ, Hussain R, Jamshed A. Pulsed radiofrequency modulation for lingual neuralgia. Br J Oral Maxillofac Surg. 2012;50:e4–e5. 8. Shabat S, Leitner J, Folman Y. Pulsed radiofrequency for the suprascapular nerve for patients with chronic headache. J Neurosurg Anesthesiol. 2013;25:340–343. 9. Van Boxem K, van Bilsen J, de Meij N, et al. Pulsed radiofrequency treatment adjacent to the lumbar dorsal root ganglion for the management of lumbosacral radicular syndrome: a clinical audit. Pain Med. 2011;12:1322–1330. 10. 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. 11. 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. 12. Chua NH, Vissers KC, Sluijter ME. Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications—a review. Acta Neurochir (Wien). 2011;153:763–771. 13. Luo F, Shen Y, Wang T, Meng L, Yu X, Ji N. 3D CTGuided pulsed radiofrequency treatment for trigeminal neuralgia. Pain Pract. 2014;14:16–21. 14. van Boxem K, van Eerd M, Brinkhuizen T, Patijn J, van Kleef M, van Zundert J. Radiofrequency and pulsed radiofrequency treatment of chronic pain syndromes: the available evidence. Pain Pract. 2008;8:385–393. 15. Kim JH, Yu HY, Park SY, Lee SC, Kim YC. Pulsed and conventional radiofrequency treatment: which is effective for dental procedure-related symptomatic trigeminal neuralgia? Pain Med. 2013;14:430–435. 16. Teixeira A, Sluijter ME. Intradiscal high-voltage, longduration pulsed radiofrequency for discogenic pain: a preliminary report. Pain Med. 2006;7:424–428. 17. Luo F, Meng L, Wang T, Yu X, Shen Y, Ji N. Pulsed radiofrequency treatment for idiopathic trigeminal neuralgia: a retrospective analysis of the causes for ineffective pain relief. Eur J Pain. 2013;17:1189–1192. 18. Cohen SP, Zundert J. Pulsed radiofrequency: rebel without cause. Reg Anesth Pain Med. 2010;35:8–10. 19. 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.
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20. Tanaka N, Yamaga M, Tateyama S, Uno T, Tsuneyoshi I, Takasaki M. The effect of pulsed radiofrequency current on mechanical allodynia induced with resiniferatoxin in rats. Anesth Analg. 2010;111:784–790. 21. 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. 22. 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.
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