Pulsed Radiofrequency 2 Hz Preserves the Dorsal Root Ganglion Neuron Physiological Ca2+ Influx, Cytosolic ATP Level, Δψm, and pERK Compared to 4 Hz: An Insight on the Safety of Pulsed Radiofrequency in Pain Management.

Background: Pulsed radiofrequency (PRF) is beneficial for radicular pain and is commonly administered at pulse frequencies of 2 or 4 Hz. However, its effects on healthy neurons have not yet been widely studied. This study aims to determine the effect of PRF at 2 Hz and 4 Hz on the physiology of healthy dorsal root ganglion (DRG) neurons. Methods: An in vitro experimental study was conducted using DRG neuron cultures divided into three groups. Control cells received no treatment, one cell group received 20 ms 2 Hz PRF for 360 s, and one cell group received a 4 Hz PRF 10 ms pulse for 360 s with similar energy. Ca2+ influx, mitochondrial membrane potential (Δψm), cytosolic Adenosine triphosphate (ATP), and phosphorylated extracellular signal-regulated kinase (pERK) levels were measured. The data were analyzed using the One-Way ANOVA variance with α=5%. Results: DRG neurons exposed to PRF 2 Hz did not experience a significant change in Ca2+ influx, whereas PRF 4 Hz caused a significant decrease in Ca2+ influx compared to the basal level. PRF at 2 Hz did not cause a change in Δψm, whereas PRF at 4 Hz caused a significant decrease in Δψm (p<0.05). Both 2 and 4 Hz PRF resulted in a significant elevation in cytosolic ATP concentration, but the 2 Hz PRF had a higher cytosolic ATP than the 4 Hz group (p<0.05). Both 2 and 4 Hz did not show a significant difference in pERK intensity with respect to the control (p>0.05), indicating that there was no significant neuron activation. Conclusion: Both frequencies did not significantly activate DRG neurons, but with similar energy delivery, PRF 2 Hz preserved the physiological properties of healthy neurons better than PRF 4 Hz did. A 2 Hz PRF is the preferred frequency in clinical applications for neuron-targeted therapy.

Identifying pain problems, healthcare professional perceptions, expectations and challenges in multidisciplinary pain center establishment.

Aim: Before establishing a multidisciplinary pain center (MPC), the pain problem, healthcare professionals (HCP) perceptions, expectations and the potential challenges of MPC establishment need to be identified. Methods: A quantitative survey study of 1058 Indonesian HCPs. The study uses a national inquiry sent by the International Association for the Study of Pain (IASP) chapter for pain. Results: 99.0% of respondents had met patients with pain as the primary complaint and acute pain as the most common complaint. Insufficient pain management in Indonesian healthcare, insufficient pain epidemiological data and unaware HCP about MPC become problems of pain management in Indonesia. However, most HCP agreed that health facilities should have MPC. Financial issues (insufficient patient insurance) were considered the most important barrier for referring patients to MPC. Conclusion: The identified core problem, HCP perceptions, expectations and challenges of MPC establishment should become a consideration in the strategic planning of MPC establishment.

Multidisciplinary pain centers (MPC) provide benefits to patients, healthcare professionals (HCP) and the community in general but are not yet established in Indonesia and other developing countries. Before establishing a MPC, the problem in pain, HCP's perceptions, expectations and challenges in MPC establishment need to be identified. From the national survey on 1058 HCP, almost all respondents (99.0%) had met patients with pain as the primary complaint and acute pain as the most common complaint (51.2%). Insufficient pain management in Indonesian healthcare, insufficient pain epidemiological data and unaware HCP about MPC have become problems in pain management in Indonesia. However, most HCP agreed that health facilities should have pain centers as well as a center for the study of pain and recommended 'pain that requires intervention' should be referred to a MPC. Financial issues such as insufficient patient insurance was considered the most important barrier for referring patients to MPCs in Indonesia. The high incidence of pain, insufficient pain management in health facilities and insufficient data on pain have become the core problem that underlies the need for MPC establishment in Indonesia. Overall, HCPs have positive perceptions and expectations regarding MPCs. Financial barriers are thought to be a potential burden in the development of MPCs. By understanding the pain problem, HCP perceptions, expectations and potential challenges on the MPC establishment, strategic planning in MPC establishment is expected to be achieved especially in developing countries.

Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate.

Background: The molecular mechanism of pulsed radiofrequency (PRF) in chronic pain management is not fully understood. Chronic pain involves the activation of specific N-Methyl D-Aspartate receptors (NMDAR) to induce central sensitization. This study aims to determine the effect of PRF on central sensitization biomarker phosphorylated extracellular signal-regulated kinase (pERK), Ca2+ influx, cytosolic ATP level, and mitochondrial membrane potential (Δψm) of the sensitized dorsal root ganglion (DRG) neuron following NMDAR activation. Methods: This study is a true experimental in-vitro study on a sensitized DRG neuron induced with 80 µM NMDA. There are six treatment groups including control, NMDA 80 µM, Ketamine 100 µM, PRF 2Hz, NMDA 80 µM + PRF 2 Hz, and NMDA 80 µM + PRF 2 Hz + ketamine 100 µM. We use PRF 2 Hz 20 ms for 360 seconds. Statistical analysis was performed using the One-Way ANOVA and the Pearson correlation test with α=5%. Results: In the sensitized DRG neuron, there is a significant elevation of pERK. There is a strong correlation between Ca2+, cytosolic ATP level, and Δψm with pERK intensity (p<0.05). PRF treatment decreases pERK intensity from 108.48 ± 16.95 AU to 38.57 ± 5.20 AU (p<0.05). PRF exposure to sensitized neurons also exhibits a Ca2+ influx, but still lower than in the unexposed neuron. PRF exposure in sensitized neurons has a higher cytosolic ATP level (0.0458 ± 0.0010 mM) than in the unexposed sensitized neuron (0.0198 ± 0.0004 mM) (p<0.05). PRF also decreases Δψm in the sensitized neuron from 109.24 ± 6.43 AU to 33.21 ± 1.769 AU (p<0.05). Conclusion: PRF mechanisms related to DRG neuron sensitization are by decreasing pERK, altering Ca2+ influx, increasing cytosolic ATP level, and decreasing Δψm which is associated with neuron sensitization following NMDAR activation.

Effective Suppression of the Polysulfide Shuttle Effect in Lithium-Sulfur Batteries by Implementing rGO-PEDOT:PSS-Coated Separators via Air-Controlled Electrospray.

Lithium-sulfur (Li-S) batteries have been earning significant attention because of their high energy density and cost efficiency. Albeit these outstanding qualities, the polysulfide shuttling effect and low electrical conductivity of the sulfur active material in this battery chemistry results in poor cycling performance. In an attempt to overcome these problems, a hybrid structure of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) and reduced graphene oxide was developed and coated on the surface of a conventional separator using air-controlled electrospray. Implementing these coated separators in Li-S batteries led to lower polarization and stymied the polysulfide shuttling effect through the combining effects of electrostatic, physical, and chemical interactions. Our results reveal that the capacity and rate capacity are drastically improved via coating the separator, leading to more than twice the capacity of over 800 mA h g-1 after 100 cycles at 0.5 C rate, when it is compared to those with the pristine separator. Overall, this hybrid coating material shows great promise in enhancing the current Li-S battery technology.

Percutaneous Cervical Nucleoplasty vs. Pulsed Radio Frequency of the Dorsal Root Ganglion in Patients with Contained Cervical Disk Herniation; A Prospective, Randomized Controlled Trial.

BACKGROUND: Cervical neck pain is often caused by cervical disk pathology and may cause severe symptoms and disability. Surgeons and patients are increasingly aware of postsurgery-related complications. This stimulated the clinical usage of minimally invasive treatments such as percutaneous nucleoplasty (PCN) and pulsed radio frequency (PRF). However, scientific evidence on both treatments is limited. OBJECTIVE: Our objective was to evaluate the efficacy of PCN compared to PRF in patients with contained cervical disk herniation. METHODS: A prospective randomized clinical trial was conducted including 34 patients with radicular pain due to a single contained cervical disk herniation who were treated with either PCN or PRF. Demographic data were collected, and the Medical Outcomes Study 12-Item Short Form (SF-12) Health Survey, visual analog scale (VAS), and the Neck Disability Index (NDI) were completed 1, 2, and 3 months after treatment. Treatment satisfaction and complications were recorded. RESULTS: In the PCN group (n = 17, mean age 52.4 years, 10 female/7 male), patients were treated at C5 to C6 (8 cases) or C6 to C7 (9 cases). In the PRF group (n = 17, mean age 49.5 years, 8 female/9 male), patients were treated at C3 to C4 (1 case), C5 to C6 (10 cases), or C6 to C7 (6 cases). At 3 months, mean pain VAS improved significantly from baseline in the PCN group (mean improvement: 43.4 points) and in the PRF group (34.0 points). However, improvement in 1 group was not superior compared to the other group (P = 0.48). No serious complications were reported. CONCLUSION: Within 3 months, both PCN and PRF show significant pain improvement in patients with contained cervical disk herniation, but none is superior to the other. Both treatment options appear to be effective and safe in regular clinical practice.

Current evidence of percutaneous nucleoplasty for the cervical herniated disk: a systematic review.

BACKGROUND: Although percutaneous cervical nucleoplasty (PCN) has been shown to be both safe and effective, its application is still debated. PCN applied in disk herniation has not been systematically reviewed before, resulting in a limited insight into its effectiveness and safety, and the quality of available evidence. Therefore, we systematically reviewed the evidence on the efficacy and safety of PCN in patients with a (contained) herniated disk. METHODS: MEDLINE, EMBASE, and the Cochrane Library (Central Register of Controlled Trials) were searched for randomized controlled trials (RCTs) and nonrandomized studies using the following keywords: "Nucleoplasty," "Cervical," "Hernia," "Herniation," "Prolapse," "Protrusion," "Intervertebral disk," and "Percutaneous disk decompression." First, all articles were appraised for methodological quality, and then, RCTs were graded for the level of evidence according a best-evidence synthesis, because a meta-analysis was not possible. Finally, the RCTs' applicability and clinical relevance also was assessed. RESULTS: Of 75 identified abstracts, 10 full-text articles were included (3 RCTs and 7 nonrandomized studies). These studies represented a total of 1021 patients: 823 patients (≥ 892 disks) were treated by PCN. All studies showed low methodological quality, except for two. The level of evidence of the RCTs was graded as moderate, with low to moderate applicability and clinical relevance. CONCLUSION: All included studies showed PCN to be an effective and safe procedure in the treatment of (contained) herniated disks at short-, mid-, and long-term follow-up. However, the level of evidence is moderate and shows only low to moderate applicability and clinical relevance.

The long-term efficacy and safety of percutaneous cervical nucleoplasty in patients with a contained herniated disk.

BACKGROUND: Percutaneous cervical nucleoplasty (PCN) is a safe and effective treatment in symptomatic patients with contained cervical herniated disks. It provides simple and efficient disk decompression, using a controlled and highly localized ablation, but evidence regarding long-term efficacy is limited. We conducted a retrospective study to investigate the long-term efficacy and safety of PCN, and the influence of ideal selection settings. METHODS: A total of 27 patients treated with PCN fulfilling ideal selection criteria (Group A) were studied and compared to 42 patients not meeting these criteria (Group B). Outcomes were assessed using the Visual Analogue Scale (VAS) and a four-level Likert item for perceived pain and satisfaction, the Neck Disability Index (NDI), and the Short Form 36 (SF-36). Additional relevant outcomes were retrieved from medical records. RESULTS: The postoperative mean VAS pain for Group A was 29.9 (SD ± 32.6) at a mean follow-up of 24 months (range: 2-45). Only 10% of these patients reported mild transient adverse events. There was a trend, but no difference between both groups in pain scores; however, treatment satisfaction was higher for Group A (74.1 ± 27.2-55.5 ± 31.4, P = 0.02). Group A also reported better physical functioning based on the Physical Component Summary (43.6 ± 10.6-37.3 ± 12.0, P = 0.03) and showed a larger proportion of patients no longer using any medication postoperatively (63-26%, P = 0.01). CONCLUSION: These results show long-term effectiveness and safety of PCN in patients with a one-level contained cervical herniated disk, and the reliance of selecting patients meeting ideal criteria for successful PCN.

Whiplash patients with cervicogenic headache after lateral atlanto-axial joint pulsed radiofrequency treatment.

BACKGROUND: Whiplash patients regard cervicogenic headache (CEH) as the most burdensome symptom of their condition. Sufferers experience a significant degree of disability from headache, associated neck pain and disability, and sleep disturbance. Lateral C1/2 joint pulsed radiofrequency (PRF) treatment has been shown to produce significant relief from headache in patients with CEH. OBJECTIVES: The objective of this retrospective questionnaire study of 45 consecutive whiplash patients with CEH who had undergone antero-lateral atlantoaxial joint pulsed radiofrequency treatment (AA PRF) was to evaluate the treatment's long-term effects on pain-related disability and health-related quality of life. PATIENTS AND METHODS: Four questionnaires were sent to all 45 patients who had undergone AA PRF: 1) The short form-36 (SF-36); 2) The neck disability index (NDI); 3) The medical outcome scale-sleep scale (MOS-SS); 4) The headache impact test-6 (HIT-6). All 45 patients received AA PRF under fluoroscopic guidance. PRF treatment was conducted at 45 V with a pulsed frequency of 4 Hz and a pulsed width of 10 ms for 4 minutes . RESULTS: Patients who responded to the procedure reported lower pain scores at 2, 6, and 12 months of follow-up compared to nonresponders. More important, patients reported marked improvements in headache impact (P < 0.01), neck-disability scores (P < 0.01), awakening due to headache (P < 0.01), and sleep problems (9-item; P < 0.05) on the MOS-SS. Responders to the procedure also reported a significantly higher health-related quality of life in terms of bodily pain (P < 0.05) and health change (P < 0.01) on the SF-36. CONCLUSIONS: In light of the inherent limitations of our retrospective study, AA PRF treatment can only be tentatively viewed as a promising treatment modality for whiplash patients with CEH and is subject to validation in future studies.

Pulsed radiofrequency treatment for trigeminal neuralgia.

BACKGROUND: Pulsed radiofrequency (PRF) treatment is defined as the delivery of short pulses of radiofrequency via a needle tip, which does not result in an actual thermal lesions. There are mixed views regarding the use of PRF for trigeminal neuralgia (TN). In our opinion, one of the main reasons for the contrasting views is the insufficient PRF dose employed in previous studies. In a recent study on the effects of PRF on resiniferatoxin-induced neuropathic pain in an animal model, the anti-allodynic effects of PRF were significantly greater when the PRF exposure duration was increased from 2 to 6 minutes. OBJECTIVES: The primary objective of this retrospective study is to report the results for 36 consecutive patients who underwent PRF treatment for TN, for 6 minutes at 45 V at a pulsed frequency of 4 Hz and a pulse width of 10 ms. PATIENTS AND METHODS: For the study, we obtained procedural records of 36 consecutive patients. Their current state of pain was evaluated over a telephonic survey and the post-procedural data at 2, 6, and 12 months were retrieved thereafter from the patient records. The main outcome measure was excellent pain relief (more than 80%), which was assessed at 2, 6, and 12 months. RESULTS: The percentages of patients who showed excellent pain relief (> 80% pain relief) at 2, 6, and 12 months were 73.5% (25/34), 61.8% (21/34), and 55.9% (19/34), respectively. The percentages of patients showing satisfactory pain relief (50-80% pain relief) at 2, 6, and 12 months were 14.7% (5/34), 17.6% (6/34), and 17.6% (6/34), respectively, and those of patients showing less than satisfactory pain relief (< 50% pain relief) at 2, 6, and 12 months were 11.8% (4/34), 20.6% (7/34), and 23.5% (8/34), respectively. No complications were reported, and none of the patients required hospitalization. CONCLUSIONS: PRF of the trigeminal ganglion should be further evaluated as an alternative treatment method for TN.

Long-term pain relief in patients with cervicogenic headaches after pulsed radiofrequency application into the lateral atlantoaxial (C1-2) joint using an anterolateral approach.

The lateral atlantoaxial joint has long been reported as a source of cervicogenic headache. We present a retrospective study, including 86 patients who had undergone lateral C1-2 joint pulsed radiofrequency application, for cervicogenic headache in a single pain center from March 2007 to December 2008. The percentage of patients who had >or=50% pain relief at 2 months, 6 months, and 1 year were 50% (43/86), 50% (43/86), and 44.2% (38/86), respectively. Long-term pain relief at 6 months and 1 year were predicted reliably by >or=50% pain relief at 2 months (P < 0.001). Apart from 1 patient that complained of increased severity of occipital headache lasting several hours, we had no other reported complications.