We evaluated the therapeutic effects of PRF in patients with idiopathic GPN and the results revealed that PRF could obtain a promising effect with an effective rate of 93.3% at 1 month postoperatively with long-term recurrence-free survival rates of 54.8% at 120 months postoperatively. The short-term efficacy we observed is consistent with that of Bharti et al, who reported a study about GPN secondary to oropharyngeal carcinoma that was treated by PRF. In their study, the treatment was effective in 23 out of 25 patients (92%), for more than 3 months without major complications. However, Bharti et al reported that the average duration of effective pain relief was only 5 to 9 months. As a result, we speculate that PRF can attain longer duration of pain relief for the treatment of idiopathic GPN than secondary GPN. However, prospective Randomized controlled trials (RCTs) are necessary to further confirm our speculation.
The efficacy of PRF is considered inferior to radiofrequency thermocoagulation for the treatment of trigeminal neuralgia (TN) . However, there is a lack of research comparing the effectiveness of PRF and radiofrequency thermocoagulation on GPN therapy. GPN is a rare debilitating form of paroxysmal facial pain, which occurs 100 times less frequently than TN. As a result, low incidence of GPN may explain the paucity of related studies. Song et al reported that the immediate pain relief rate in idiopathic GPN patients treated with radiofrequency thermocoagulation was 82.1%, and long-term pain relief was 44.2% at 10 years, and 39.3% at 12.5 years postoperatively. Based on our research, it appears that PRF could attain greater effective rate than radiofrequency thermocoagulation treatment, probably because the definitions of observing a response in the two studies are different. In our study, the effective rate is defined as the percentage of patients with NRS reduction of more than 50% while in Song et al’ s study, the effective rate was defined as the percentage of patients classified into Barrow Neurological Institute (BNI) class I and BNI class II outcome. Moreover, the participants included in our study were idiopathic GPN patients without any history of invasive treatments, whereas, 27 (23.1%) patients in Song et al’ s study underwent prior procedures such as nerve block, radiofrequency thermocoagulation, stereotactic radiosurgery or MVD. Therefore, the GPN patients in Song et al’ s study might have been more intractable than that in our research. In addition, the treatment efficacy is perhaps associated with the technical level of pain specialists and different intraoperative imaging modalities. Prospective randomized controlled clinical trials remain to be conducted to further compare the efficacy of PRF and radiofrequency thermocoagulation, for the treatment of GPN.
There were 2 cases who did not respond to PRF treatment in our study. We assume this was probably due to the patient’s family history of GPN or the patient’s over a decade long history of GPN, which we suspect to be more intractable. However, whether family history or disease duration are factors influencing treatment outcomes, are yet to be studied. Recurrence could occur with any treatments, including radiofrequency thermocoagulation, gamma knife radiosurgery, and MVD; 5 cases relapsed in our study. Up to now, the etiology of pain recurrence is not clear. Therefore, additional studies on the prevention of pain relapse are required to further improve the long-term outcomes of GPN patients.
It is worth noting that the patients in our study did not achieve excellent pain relief immediately after undergoing PRF, but rather required a median interval latency of 3 days (IQR,2–5; range,1–14 ) and two cases needed even more than 10 days to achieve satisfactory results. The interval latency is consistent with our previous studies on PRF for the treatment of supraorbital neuralgia, infraorbital neuralgia, and TN[32–34]. We assume the reason for the existence of a recovery period is because PRF could cause plastic changes in pain transmission pathways and result in slow neuromodulation, which would require longer time to take effect. Therefore, after receiving PRF procedure, individual variations in posttreatment protocols should be taken into consideration, such as: adjusting oral analgesics to assist patients in getting through the recovery period without progression of pain intensity.
In our previous study, we found that the efficacy of PRF treatment was positively correlated with the output voltage. Subsequently, prospective, randomized, double-blinded studies have certified that high-voltage PRF is more effective than standard-voltage in treating idiopathic TN and refractory infraorbital neuralgia[33, 36]. However, there is a lack of research evaluating the effectiveness and safety of high-voltage PRF on the treatment of idiopathic GPN patients. Furthermore, whether the improvement of other parameters such as pulse frequency, pulse width, temperature, or treatment time could attain more satisfactory efficacy remains to be studied further.
PRF is an effective and safe method which has been applied in the treatment of diverse neuropathic pain such as TN, occipital neuralgia, postherpetic neuralgia, and pudendal Neuralgia [21, 37, 38]. Different from radiofrequency thermocoagulation, this method works by delivering high-frequency current to targeted nerve without heat-induced tissue damage. In this study, PRF caused less complications such as dysphagia, lingual numbness and abnormal sensation, pharynx and larynx numbness, hoarseness as well as abnormal sense of taste, compared to Song et al ’s research, which reported the efficacy of radiofrequency thermocoagulation for GPN therapy . Furthermore, PRF related postoperative complications were slighter in this study, and disappeared earlier than radiofrequency thermocoagulation related complications because PRF is a treatment technology with micro-destructiveness. One patient developed bradycardia during the operation due to vagal stimulation, who immediately resumed sinus rhythm after the administration of atropine, which suggests that close hemodynamic monitoring is necessary to ensure the safety of patients during the procedure. In our study, no patient developed infection, as all procedures were performed in sanitary conditions with utmost precautionary measures. Additionally, the choice of percutaneous approach to target glossopharyngeal nerve may be related to the incidence of complications. Intraoral method is commonly performed for preemptive analgesia, and is associated with the risk of infection and may cause iatrogenic damage to several structures including vagus nerve, internal carotid artery, vertebral artery, brainstem, and upper cervical spinal nerves. Besides, in early years, medial part of the jugular foramen approach was used for radiofrequency treatment on GPN patients. However, glossopharyngeal nerve, vagus nerve and accessory nerve pass through together at the level of the jugular foramen, this increases the possibility of damaging nearby cranial nerves and internal carotid artery. At the styloid process level, glossopharyngeal nerve, vagus nerve and accessory nerve separate from each other, and cranial nerve IX becomes the most adjacent nerve to the distal part of the styloid process. Hence, we chose the tip of the styloid process as the target, which is consistent with Bharti et al ’s study. In addition, all patients underwent CT-guided treatment, in which clear visualization of the anatomic structures was ensured and neurovascular injury and puncture to adjacent structures was avoided.
Our study has several limitations. Firstly, this is a retrospective case series report with a small sample size which unavoidably caused some selection bias. Therefore, prospective, randomized controlled researches with larger sample sizes as well as higher level of evidence are needed to further validate our outcomes. However, it will be quite difficult to conduct RCT studies due to the low incidence of GPN. Secondly, only patients with idiopathic GPN were included in our research. The long-term outcome of PRF for the treatment of secondary GPN remains to be studied further. Finally, although PRF treatment under the guidance of CT increases the rate of successful punctures and decreases the incidence of complications caused by inaccurate punctures, patients are inevitably exposed to radiation energy which may lead to safety concerns. In recent years, ultrasonography has been proven to be a safer and easier imaging modality, without ionizing radiation[32, 42]. Further investigations for the therapeutic efficiency of ultrasound-guided PRF operation on glossopharyngeal nerve is of great importance.