Korean J Pain 2022; 35(1): 114-123
Published online January 1, 2022 https://doi.org/10.3344/kjp.2022.35.1.114
Copyright © The Korean Pain Society.
Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China
Correspondence to:Ming Yao
Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, No. 1882 South Zhonghuan Road, Nanhu District, Jiaxing 314001, Zhejiang, China
Handling Editor: Younghoon Jeon
*These authors contributed equally to this work.
Received: September 11, 2021; Revised: October 28, 2021; Accepted: November 12, 2021
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Different views have been proposed on the radiofrequency treatment modes and parameters of radiofrequency thermocoagulation of the spinal dorsal root ganglion for the treatment of postherpetic neuralgia (PHN). It is urgent to identify a more effective therapy for patients with PHN.
Methods: Patients who underwent radiofrequency thermocoagulation therapy for PHN were retrospectively reviewed and were divided into a radiofrequency thermocoagulation (CRF) and double neddles radiofrequency thermocoagulation (DCRF). The pain scores (numerical rating scale, NRS) were evaluated at the following time points: before the operation, 1 day, 3 months, 6 months, 1 year, and 2 years after operation. The incidence of complications and the degree of pain relief were evaluated. The in vitro ovalbumin experiment was used to indicate the effects of radiofrequency thermocoagulation.
Results: Compared with the preoperative NRS scores, the postoperative NRS scores decreased significantly; the NRS scores of the DCRF group was lower than that of the CRF group at all time points from 6 months to 2 years following the operation. The total effective rate of the DCRF group was significantly higher than that of the CRF group at 2 years following the operation. The incidence of numbness in the DCRF group was higher than that noted in the CRF group. The ovalbumin experiments in vitro indicated that the effects of radiofrequency thermocoagulation were optimal when the distance between the two needles was 5 mm.
Conclusions: DCRF with a 5 mm spacing exhibits a longer duration and higher effective rate in the treatment of PHN and is worth promoting.
Keywords: Chronic Pain, Electrocoagulation, Ganglia, Spinal, Herpes Zoster, In Vitro Techniques, Incidence, Needles, Neuralgia, Postherpetic, Ovalbumin, Pain Management, Radiofrequency Therapy, Spine.
Herpes zoster is caused by the varicella-zoster virus, which infects the dorsal root ganglion (DRG) or cerebral nerve [1,2]. It is common in middle-aged and elderly people with impaired immunity. The main risk factors include woman gender, family history, and autoimmune diseases . Although the herpes zoster vaccine has been widely used in certain countries [2,4,5], recent studies have shown that the prevalence rate of this virus continues to rise and that the age of the disease exhibits a downward trend [6,7]. When the cellular immune function of the host is low, the virus is activated again, causing inflammation and necrosis of the ganglia. Concomitantly, the activated virus can move along the peripheral nerve fibers to the skin to develop herpes, which is associated with pain . Its severity usually depends on the presence of pain before the formation of the rash, the severity of the rash, sex, age, and impaired immune function [8-10].
Radiofrequency therapy of the spinal DRG is considered to be one of the most effective intervention methods for the treatment of postherpetic neuralgia (PHN) due to its small trauma, effective control, high safety, optimal accuracy, and reliable repeatability. This method has been widely used previously [11,12]. Pulsed radio frequency (PRF) is considered to regulate only the nerve and therefore causes almost no nerve damage . Radiofrequency thermocoagulation is considered to cause nerve damage, resulting in side effects, such as hypoesthesia and decreased muscle strength . However, the effective rate of PRF alone in the clinical treatment is low and its effective time is short .
Unipolar radiofrequency means that a single radio frequency puncture needle reaches the operation site, and the other electrode is attached to the body surface, thus forming a large, closed loop. When the radio frequency needle encounters the impedance of human tissue, it produces heat energy and achieves the effect of radiofrequency thermocoagulation. Bipolar radio frequency means that two radio frequency puncture needles reach the operation site and form a small, closed loop in the operation area. According to the impedance of human tissue between the two needles, heat energy is generated to achieve the effect of radiofrequency thermocoagulation. The main difference between the two patterns is that in the unipolar radiofrequency the current passes through the skin tissue where it is lost mainly in the form of radiation heating; while in the bipolar radiofrequency, the current is relatively more concentrated between the needles in the form of linear heating.
Therefore, it is urgent to seek a newer and more effective radiofrequency therapy for patients with PHN. The purpose of this study was to compare the effective rate, effective maintenance time and complications of bipolar and unipolar radiofrequency thermocoagulation of the spinal DRG in the treatment of PHN, so as to guide clinical practice.
A total of 60 patients that underwent radiofrequency thermocoagulation therapy for PHN in the Pain Department of the Affiliated Houspital of Jiaxing University from January 2013 to November 2017 were retrospectively reviewed. Among them, 34 males and 26 females were present, aged from 49 to 93 years, with an average age of 72.5 ± 9.4 years. Radiofrequency thermocoagulation of the spinal DRG was performed by the same doctor with sufficient clinical pain management experience. All patients signed an informed consent form, and our study was conducted in accordance with the Declaration of Helsinki. Moreover, this study was examined and approved by the Ethics Committee of the First Hospital of Jiaxing (LS-2010-119).
1) The following inclusion criteria were used: (1) The subjects met the clinical diagnostic criteria of post-herpetic neuralgia; (2) The age of the subjects was higher than and/or equal to 18 years; (3) The diseased region of the herpes zoster only involved the unilateral trunk nerve, that is, the thoracic 1-12 nerve; (4) The subjects’ numerical rating scale (NRS) score was higher than 4 when they were admitted to the hospital; (5) The course of the herpes zoster disease was ≥ 3 months; (6) The subjects underwent radiofrequency thermocoagulation (CRF) or double neddles radiofrequency thermocoagulation (DCRF); (7) All the subjects agreed and received follow-up by telephone.
2) The following exclusion criteria were used: (1) Patients with a history of malignant tumors; (2) Patients that had received immunosuppressive therapy; (3) Uncooperative patients with mental illness, mental retardation, or confusion; (4) Patients with severe liver, kidney, heart, and lung diseases; (5) Patients that had received a history of invasive treatment prior to operation; (6) Patients that withdrew from the operation due to lack of cooperation with the surgeon during the procedure; (7) Patients that had received other invasive treatment or other surgeries following the operation; (8) Patients with herpes zoster at the lumbar segmental level; (9) Patients that lacked basic information and could not be followed up following the operation.
The patients were selected according to the inclusion and exclusion criteria and all patients were divided into the bipolar group (DCRF group, n = 24) and the unipolar group (CRF group, n = 36) by reviewing their intraoperative imaging data.
The patients entered the computed tomography (CT) treatment room and laid in a prone position on the treatment bed. A positioning grid was placed at the patient’s preoperative mark and fixed with adhesive tape (Fig. 1A, 2A). Then, with the help of CT software, the puncture target was pre-designed, and the puncture depth and angle were calculated (Fig. 1B, 2B, 2C). After that, local infiltration of anesthesia was performed with 2% lidocaine (Hubei Tianyao Pharmaceutical Co., Ltd., Xiangyang, Hubei, China) at a volume of 0.5 mL. Under the guidance of CT (Siemens SomatomEmotion system - Siemens HealthCare, Malvern, PA), the puncture needle (Inomed Health Ltd, Hopwood Lane, Halifax, Germany) was used to create a puncture following the preset angle and the path to the specified position. In the CRF group, a single puncture needle was used to puncture a pre-designed target (Fig. 1C). In the DCRF group, two puncture needles were inserted from different angles towards the pre-designed target (Fig. 2D).
Following completion of the initial puncture, a CT scan was performed again to confirm the needle placement. Further adjustment of the direction of the needle was performed to the outlet of the nerve root at the ventral superior edge of the intervertebral foramen in the affected area. Then the radiofrequency (RF) device (Baylis Medical Company Inc., Toronto, ON, Canada) was connected and the following tests were performed: (1) The sensory stimulation was carried out under 50 Hz and 0.1 ms and the current threshold inducing abnormal pain sensation was observed to judge the accuracy of the puncture site and record the current (mA) at this time. (2) The motor stimulation was carried out under 2 Hz and 1.0 ms in order to observe the current threshold that could make the muscle beat in the area, which was innervated by the DRG, and to record the current (mA) at the same time. Subsequently, the tip position was adjusted again until the movement and sensation areas were completely covered, without affecting the normal area. Finally, the radio frequency parameters were set. The parameters of the patients in the CRF and DCRF groups were both 95°C and 300 seconds [15,16]. During the operation, patients didn’t receive any additional blocks, the reaction of the patients was observed, and the incidence of the complications was assessed. A record from all the patients was made.
The preoperative data included age, sex, pain course, pain location, and preoperative pain NRS score , as well as the NRS score 1 day following the operation. The postoperative data included the NRS score, pain relief, operative complications, and side effects at 3 months, 6 months, 1 year, and 2 years, all of which were evaluated by telephone follow-up. The medical staff in the non-operation group followed up the patients by telephone.
Pain was measured with a pain NRS score, ranging from 0 (no pain) to 10 (the most unbearable pain). The degree of pain relief was evaluated according to the curative effect of the patient 2 years following the operation. The curative effect was divided into 4 grades (a, b, c, d) according to the ratio of (the difference between preoperative NRS and postoperative NRS scores)/preoperative NRS score × 100%. The following grades were defined as follows [18,19]: (a) complete relief (CR), pain relief more than 75%; (b) partial relief (PR), pain relief 50 to 75%; (c) mild relief (MR), pain relief 25 to 50%; and (d) unresponsive relief, pain relief less than 25%. The total effective rate (%) was defined by the following equation: [(CR + PR + MR)/n] × 100% and the marked rate (%) = [(CR + PR)/n] × 100%.
In addition, the incidence of the complications, including short-term pneumothorax, such as hematoma, infection and spinal cord injury, and the long-term complications, such as numbness in the corresponding innervated areas and abdominal dilatation were recorded. Moreover, the incidence of numbness and abdominal distension was calculated in the affected area.
The analysis of the clinical data of the patients suggested that the marked rate of 2 years after the surgery was 53.33% in the CRF group and 94.74% in the DCRF group. The power of the study was estimated at 90%, with a 95% confidence interval and a 2-sided type I error of 5%. Therefore, the present study required 19 patients in each treatment arm. To compensate for patients who may have been lost to follow-up, 60 patients were reviewed for the two groups. Among them, 36 patients were included in the CRF group and 24 patients in the DCRF group.
The SPSS ver. 25.0 (IBM Co., Armonk, NY) was used for statistical analysis. The frequency was used as the main variable for the classification of the groups. The normality of the distribution was tested by the Kolmogorov–Smirnov test. The variables of the non-normal distribution were presented by the median (quartile spacing) and were compared by the Mann–Whitney
The comparison of the basic demographic and clinical data of the two groups prior to the operation indicated no significant differences between the two groups in terms of sex, age, course of pain, location of pain and, NRS score prior to the operation (Table 1).
The results of the electrophysiological test indicated that the sensory test of the CRF group was 0.39 ± 0.12 (mA), whereas the DCRF group was 0.36 ± 0.11 (mA),
The preoperative NRS scores and the postoperative scores at 1 day, 3 months, 6 months, 1 year, and 2 years in the CRF group are shown in Table 3. The postoperative NRS score at each time point was lower than that prior to the operation. The difference was significant (Table 3).
The preoperative NRS scores, and scores at postoperative day 1, 3 months, 6 months, 1 year, and 2 years in the DCRF group are shown in Table 3. The postoperative NRS score at each time point was lower than that prior to the operation and the difference was statistically significant (Table 3).
No significant differences were noted in the NRS score between the DCRF and CRF groups prior to the operation and at day 1 and 3 months following the operation. However, at 6 months following the operation, the NRS score of the DCRF group was significantly lower than that of the CRF group. This effect was noted for the first time. Subsequently, at all the time points from 6 months to 2 years following the operation, the NRS score of the DCRF group was significantly lower than that of the CRF group (Table 3).
From the follow-up, at 2 years following the operation, the marked rate of the CRF group (53.33%) was significantly lower than that of the DCRF group (94.74%). This was our primary outcome. No significant differences were noted in the marked rate at other time points. The total effective rate of the CRF and DCRF groups at each time point following the operation is shown in Table 4. No significant differences were noted between the two groups (Table 4).
The main operative complications were pneumothorax, spinal cord injury, hematoma, infection, numbness, and abdominal distension. The review of the disease history of the patients demonstrated no intraoperative complications in the aforementioned two groups.
No short-term postoperative complications were noted in both groups. However, observation of long-term postoperative complications demonstrated that all patients exhibited varying degrees of skin numbness in the corresponding innervation area, whereas certain patients had abdominal distension. No other serious or permanent complications and side effects were observed during the follow-up period. The statistical results of the incidence of long-term postoperative complications are shown in Table 5. Significant differences were noted in the incidence of numbness at each time point between the two groups, whereas no significant difference was noted in the incidence of abdominal distension between the two groups (Table 5).
1) The length, width, and height of coagulation at different time points during the ovalbumin
2) The final coagulant weight of each group in the ovalbumin
Based on the above experimental results of the ovalbumin
In recent years, radiofrequency therapy has been widely recognized due to its high success rate, optimal efficacy, high safety, and high patient satisfaction. It has gradually become one of the mainstream methods for the treatment of neuralgia. Previous research studies on its mechanism have been carried out gradually.
Previous studies have shown that PRF can regulate the synaptic plasticity of nerve cells through
At present, in the clinic, radio frequency current is used to treat neuralgia  and has been used extensively, such as in cases of paroxysmal collective headache , primary trigeminal neuralgia [15,21-23], glossopharyngeal neuralgia , PHN [11,12,25,26], chronic knee pain , and postherpetic trigeminal neuralgia . In addition, certain studies on the use of different radio frequency modes for the treatment of neuralgia have been carried out consecutively. Previous studies have shown that the effect of simple pulsed radiofrequency is not successful, whereas the therapeutic effect of pulsed radiofrequency combined with radiofrequency thermocoagulation is suitable for its clinical use [22,23]. In the comparative study of unipolar and bipolar groups, it has been found that the bipolar group exhibited more advantages in pain relief and functional recovery [15,27].
In the clinical treatment of PHN, discussion and research on unipolar and bipolar radiofrequency have not been reported. In the present study, an electrophysiological test was used to evaluate whether the puncture was in the correct place for clinical applications. The data demonstrated that when the electrophysiological test results were within 1.0 mA, the puncture needle was close to the target ganglion, suggesting that the puncture was in the correct place.
Moreover, the incidence of numbness in the DCRF group was higher than that in the CRF group at each time point. It is interesting to note that certain patients had abdominal distension following the operation. Therefore, we conducted follow-up statistics on this initial result. The results indicated no significant differences in the incidence of abdominal distension between the two groups. However, the association between this phenomenon and the procedure’s curative effects requires further investigation.
Previous studies have suggested that the extension of the time of radiofrequency exposure is not an effective method for the treatment of neuropathic pain and excessive exposure is associated with increased neuronal damage [13,29]. In order to assess the optimal thermal coagulation effect in the bipolar procedure more clearly, we explored the radio frequency duration and bipolar distance in the ovalbumin
Through the above research, it was found that if the radio frequency time is prolonged as much as possible, which means increasing the degree or extent of damage, there would not be more complications or more harm to patients. In the future, in order to achieve better clinical treatment results, we will try to further increase the scope of surgical damage, in order to achieve better clinical treatment results. In the end, we want to do a single treatment which is permanently effective.
The present study exhibits certain shortcomings. First of all, it is a single-center study with relatively limited clinical samples. Secondly, we followed-up the subjects to a maximum time duration of 2 years after the operation. Therefore, we may need to increase the follow-up time to further clarify the curative effect, such as at 3 years and 5 years after the operation. Furthermore, in the ovalbumin
To sum up, radiofrequency thermocoagulation of the bipolar DRG exhibited a longer duration in the treatment of PHN and the effects of radiofrequency thermocoagulation were optimal when the distance between the two electrodes was 5 mm, which is helpful in guiding clinical work and providing more effective treatment for patients.
In summary, bipolar spinal DRG radiofrequency thermocoagulation has a long duration and high rate of effectiveness in the treatment of PHN. DCRF with a 5 mm spacing exhibits a longer duration and higher rate of effectiveness in the treatment of PHN. Therefore, it may be a new choice for the clinical treatment of PHN.
The authors of this project are very grateful for the understanding and support of the patients and their families who participated in this study.
Jianjun Zhu: Investigation; Ge Luo: Formal analysis; Qiuli He: Data curation; Ming Yao: Project administration.
No potential conflict of interest relevant to this article was reported.
The present study was supported by the National Natural Science Foundation of China (81901124), Natural Science Foundation of Zhejiang Province of China (LY20H090020, LGF20H090021, LQ19H090007), Key Discipline Established by Zhejiang Province and Jiaxing City Jointly --Pain Medicine (2019-ss-ttyx) and Jiaxing Key Laboratory of Neurology and Pain Medicine.