Comparison of two distinct needle tip positions in pulsed radiofrequency for herpes zoster‐related pain

Abstract Background Herpes zoster (HZ)‐related pain, characterized by chronic and persistent pain with a dermatomal distribution, is a relatively common complication of HZ. Pulsed radiofrequency (PRF) can effectively relieve HZ‐related pain. There is no study on the effect of the needle tip position in patients with HZ for PRF treatment. This prospective study was conducted to compare two distinct needle tip positions in PRF for HZ‐related pain. Methods Seventy‐one patients suffering from HZ‐related pain were enrolled in this study. According to the dorsal root ganglion (DRG) position and needle tip position, patients were randomly allocated to the IP group (group inside of the pedicle, n = 36) and OP group (group outside of the pedicle, n = 35). Quality of life and pain control were evaluated with the visual analog scale (VAS) and activities of daily living questionnaires (including 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life), which were administered before therapy and at intervals of 1, 7, 30, and 90 days after therapy. Results Before therapy, the mean pain score was found to be 6.03 ± 0.45 in the IP group and 6.00 ± 0.65 in the OP group (p = 0.555). No significant differences were found when the two groups were compared at 1 and 7 days after therapy (p > 0.05). But, the pain score was significantly lower in the IP group at 30 days (1.78 ± 1.31 vs. 2.77 ± 1.31, p = 0.006) and 90 days of follow‐up (1.29 ± 1.19 vs. 2.15 ± 1.74, p = 0.041). Significant differences between the two groups in terms of general activity (2.39 ± 0.87 vs. 2.86 ± 0.77, p = 0.035), mood (1.97 ± 1.65 vs. 2.86 ± 1.50, p = 0.021), relations with other people (1.94 ± 0.92 vs. 2.51 ± 1.22, p = 0.037), sleep (1.64 ± 1.44 vs. 2.97 ± 1.44, p < 0.001), and enjoyment of life (1.58 ± 1.11 vs. 2.43 ± 1.33, p = 0.004) were detected after the 30‐day follow‐up. In addition, scores for the activities of daily living were significantly lower in the IP group than that in the OP group at 90 days after therapy (p < 0.05). Conclusion The needle tip position had an influence on the PRF treatment in patients with HZ‐related pain. Positioning the needle tip in the area between the medial and lateral edges of adjacent pedicles offered good pain relief and improved quality of life in HZ patients.


| INTRODUC TI ON
Herpes zoster (HZ) is caused by the reactivation of latent varicellazoster virus (VZV) and has an asymmetrical dermatomal rash and synchronous occurrence of skin lesions. 1 HZ-related pain, characterized by chronic and persistent pain with a dermatomal distribution, is a relatively common complication of HZ. Most of the patients with HZ experience symptoms of pain. If the pain persists at least 90 days after rash onset, it is defined as postherpetic neuralgia (PHN). The incidence of HZ and PHN is 25%-30% and 10%-20%, respectively. 2,3 It is well known that spontaneous ongoing pain could lead to anxiety, depression, and even physical and psychological dysfunction. The neuralgia could not only cause considerable suffering but also affect the quality of life, leading to a societal healthcare burden. 4,5 Therefore, pain control and improving quality of life in patients with HZ are considered the main goals in the evaluation of treatment options.
To date, pulsed radiofrequency (PRF) has been an effective option for pain control and the prevention of PHN. Kim et al. 6 reported that PRF to the dorsal root ganglion (DRG) could provide better pain relief, particularly in patients who received PRF early after HZ onset.
Similarly, Huang et al. 7 showed that PRF treatment in the DRG was superior to that in the intercostal nerve, with improvements in visual analogue scale (VAS) and SF-36 scores in PHN patients. It is well known that PRF is a technique that applies short pulses of RF signals. PRF occurs through RF generators which can produce transient pulsed RF current. 8,9 The RF generator uses alternatively repeated electrical stimulation, maintaining the temperature of the neural tissue below 42°C. 10 In PRF, the short duration and resting phase between pulses can avoid apoptosis and necrosis of histocytes. 11 Although PRF can offer pain relief, it faces some problems. Ding et al. 12 found that the total effective rates of PRF in different stages (acute stage, subacute stage, and chronic stage) of HZ were 88%, 72%, and 52%, respectively. The authors concluded that the analgesic effect of PRF lasted longer in the acute phase but was lowest in the subacute and chronic phases. Luo et al. 13 reported that PRF had a high short-term recurrence rate in HZ patients. In addition, increasing evidence suggests that the voltage and the cycles were related to the therapeutic effect of PRF. High-voltage and long-duration PRF can reduce pain degree and improve the quality of life. 14 It has been shown that PRF can reduce HZ-related pain, but the poor efficacy of the treatment in some patients was quite confusing. At present, studies have demonstrated that needle tip position was significantly related to treatment effects. [16][17][18] The DRG is the primary neuron for sensory transmission and the target structure in the PRF treatment. Positioning the needle tip to the optimal DRG targets is a key point for the success of the PRF treatment. In fact, placing the needle tip in the area between the medial and lateral edges of adjacent pedicles or outside of the pedicle can relieve pain in HZ patients. However, few studies have evaluated the effect of needle tip position on pain relief in HZ patients after PRF therapy.  The sample size was calculated by G power software (version 3.1), with a two-sided 0.05 significance level and assuming an error of 5%. According to the reduced VAS scores and the effectiveness of PRF therapy (80% statistical power), a minimum of 35 patients per group were required.
The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of Wuhan No. 1 Hospital.
All patients were asked to sign an informed consent document. The diagnosis of HZ was based on typical manifestations such as a vesicular, painful dermatomal rash. 1 Inclusion criteria were as follows: age over 18 years, ability to speak Chinese, VAS score ≥4, barrierfree communication, and thoracic or lumbar nerve root involvement.
Disease-related or patient-related exclusion criteria were HZ with spinal tumor, thoracic or lumbar fracture, severe spinal stenosis, severely herniated disc, systemic infection, incomplete data in our center, and the failure of PRF therapy.

| Measurements
The first step in treating HZ-related pain was antiviral therapy and drug therapy (such as gabapentin, pregabalin, or analgesics). PRF therapy was considered for HZ patients who had not responded to medical therapy.
The PRF operation process was as follows. The patient was placed on the operating table in a prone position. The patient was connected to electrocardiogram monitoring, and low-flow oxygen (2 L/min), ensuring the patient's vital signs were normal. The skin was disinfected and sterile covered. One-percent lidocaine 3 mL was applied to the local anesthesia. Under digital subtraction angiography guidance, the needle was punctured into the target site ( Figure 3).
Once the final needle was close to the DRG position between lines A and B (IP group) or lateral to line A (OP group), a sensory stimulation test was conducted at 50 Hz, 0.5 v. The area evoked by the sensory stimuli was almost identical to the pain area in the herpes-infected area. This criterion was judged to be a successful operation. Next, motor stimulation was tested at 2 Hz. PRF was performed at 42°C (electrode tip temperature), 2 Hz (pulse frequency), 20 ms (pulse width), 120 s (single duration), and three cycles. Finally, 4 mL of the liquid local anesthetic mixture (2% lidocaine 1 mL + dexamethasone 2 mL + 0.9% normal saline 1 mL) was injected into the DRG position. 19

| Questionnaire
The VAS and activities of daily living were used to evaluate pain In our study, the VAS and activities of daily living were assessed before therapy (baseline) and at intervals of 1, 7, 30, and 90 days after therapy.

| Statistics
SPSS software (version 22.0 SPSS Inc., Chicago, IL) was used to perform the statistical analyses. Kolmogorov-Smirnov test was used to assess the normality of data distribution.
Demographic and clinical data for patients with HZ-related pain were described using the mean ± SD and count (percentage) to represent continuous and categorical variables, respectively. A t test or chi-square test was used to compare the data between the groups.
The data of VAS and activities of daily living were assessed using the Mann-Whitney U test. Graphical representations were performed by Origin software (version 2022, Origin Lab, USA). p < 0.05 was considered statistically significant.

| Pain and activities of daily living assessment
Before therapy, the mean pain score was found to be 6.03 ± 0.45 in the IP group and 6.00 ± 0.65 in the OP group (p = 0.555). No significant differences were found when the two groups were compared at 1 and 7 days after therapy (p > 0.05). But the pain score was significantly lower in the IP group at 30 days (1.78 ± 1.31 vs. 2.77 ± 1.31, p = 0.006) and 90-day of follow-up (1.29 ± 1.19 vs. 2.15 ± 1.74, p = 0.041) (Figure 4). Figure 5 shows that both the two groups had equivalent outcomes with regard to activities of daily living before therapy, at 1 day, and 7 days after therapy (p > 0.05). Significant differences between the two groups in terms of general activity (2.39 ± 0.87 vs.

| Adverse events
Numbness at the site of the skin puncture occurred in two patients in the IP group and one patient in the OP group. This symptom

| DISCUSS ION
This is the first prospective study on two distinct needle tip positions in PRF for HZ-related pain. In this study, it was shown that the patients in the IP group had significantly better pain relief and higher activities of daily living than that in the OP group.  There were some limitations in the study. First, the main limitation of our study was that the sample size was small and the follow-up period was short, which may affect the reliability of this study. Second, morphine equivalent consumption may not be quantified. We could not standardize pain therapies after discharge, resulting in a potential bias of follow-up results. Third, the pathologic anatomy of the DRG may differ in the spine. Radiologically, there were three types of the location of the DRG (intraspinal, foraminal, and extraforaminal). In this study, we only considered foraminal and extraforaminal DRG because previous research found that the intraspinal types only occurred at the L5 level in the lumbar spine, and the incidence of the variation was 5.7%. 31 In this study, PRF treatment of the DRG was applied to both the lumbar spine and the thoracic spine. The variants of the DRG may lead to biased findings. In addition, pain severity, character, and timing may vary in the course of HZ. The pain appears to be easier to control in the early stages of the disease and it can be difficult to relieve pain once it persists longer than 3 months. In our experience, some patients in the stage of postherpetic neuralgia did not respond to medical therapy, nerve block, PRF therapy, and spinal cord stimulators. They required analgesics and eventually became addicted. Therefore, the pain having many forms in different stages of HZ may have an impact on the effect of PRF.
In conclusion, the position of the needle tip had an influence on the PRF treatment in patients with HZ-related pain. Positioning the needle tip in the area between the medial and lateral edges of adjacent pedicles offered good HZ-related pain relief and improved quality of life.

CO N FLI C T O F I NTER E S T S TATEM ENT
The authors have no funding and conflicts of interest to disclose.

DATA AVA I L A B I L I T Y S TAT E M E N T
Detailed data are available from the corresponding author upon reasonable request.