The Anti-Inflammatory Action of Pulsed Radiofrequency-A Hypothesis and Potential Applications.

In 2013, it was reported that pulsed radiofrequency (PRF) could be applied to obtain a systemic anti-inflammatory effect. Patients with chronic pain and patients with an inflammatory condition from other disciplines could potentially profit from this finding. At that time, intravenous application was used, but since then, it became clear that it could be applied transcutaneously as well. This procedure was named RedoxPRF. This can be used both for regional and for systemic application. Recently, the basic element of the mode of action has been clarified from the analysis of the effects of PRF on a standard model of muscle injury in rats. The objective of this paper is to present a hypothesis on the mode of action of RedoxPRF now that the basic mechanism has become known. Cell stress causes an increased production of free radicals, disturbing the redox equilibrium, causing oxidative stress (OS) either directly or secondarily by other types of stress. Eventually, OS causes inflammation and an increased sympathetic (nervous) system activity. In the acute form, this leads to immune paralysis; in the chronic form, to immune tolerance and chronic inflammation. It is hypothesized that RedoxPRF causes a reduction of free radicals by a recombination of radical pairs. For systemic application, the target cells are the intravascular immune cells that pass through an activated area as on an assembly line. Hypothesis conclusions: 1. RedoxPRF treatment works selectively on OS. It has the unique position of having a point of engagement at the most upstream level of the train of events. 2. RedoxPRF has the potential of being a useful tool in the treatment of inflammatory diseases and possibly of stage 4 cancer. 3. In the treatment of chronic pain, RedoxPRF is an entirely new method because it is different from ablation as well as from stimulation. We propose the term "functional restoration". 4. Controlled studies must be conducted to develop this promising new field in medicine further.

Intravenous application of pulsed radiofrequency-4 case reports.

It has been suggested that PRF might possibly have an effect on the immune cells. We considered using the intravenous route to apply PRF in conditions that are caused by an unresolved immune action or connected to allostatic load, implicating an abnormally reacting immune system to obtain a systemic effect that could possibly be an additional tool in treating some of these conditions. These manuscript reports four cases that illustrate the wide variety of conditions where this new technique might be helpful.

The Treatment of Joint Pain with Intra-articular Pulsed Radiofrequency.

BACKGROUND: The intra-articular (IA) application of pulsed radiofrequency (PRF) for pain in small and large joints represents a recent development that has proven to be effective in many cases. We performed a retrospective study of 89 such procedures in 57 consecutive patients with chronic articular pain. OBJECTIVES: The aim of this retrospective study is to evaluate the effectiveness of intraarticular PRF in a group of 57 consecutive patients with chronic joint pain. PATIENTS AND METHODS: Patients with intractable joint pain for more than 6 months were treated with IA PRF 40-45V for 10-15 min in small joints and 60V for 15 min in large joints using fluoroscopic confirmation of correct needle position. A total of 28 shoulders, 40 knees, 10 trapezio-metacarpal, and 11 first metatarso-phalangeal joints were treated. Results were evaluated at 1, 2, and 5 months. The procedure was repeated after 1 month in 10 patients with initial suboptimal results. Success was defined as a reduction of pain score by at least 50%. RESULTS: All groups showed significant reductions in pain scores at all three follow-up visits. Success rates were higher in small joints (90% and 82%, respectively) than large ones (64% and 60%, respectively). Interestingly, IA PRF was successful in 6 out of 10 patients who had undergone previous surgery, including 3 with prosthetic joint replacement and in 6 of the 10 repeated procedures. There were no significant adverse effects or complications. CONCLUSIONS: IA PRF induced significant pain relief of long duration in a majority of our patients with joint pain. The exact mechanism is unclear, but may be related to the exposure of immune cells to low-strength RF fields, inducing an anti-inflammatory effect. The success rate appears to be highest in small joints. We recommend additional research including control groups to further investigate and clarify this method; our data suggest that it may represent a useful modality in the treatment of arthrogenic pain.

Changes in pain behavior and glial activation in the spinal dorsal horn after pulsed radiofrequency current administration to the dorsal root ganglion in a rat model of lumbar disc herniation: laboratory investigation.

OBJECT: Herniated discs can induce sciatica by mechanical compression and/or chemical irritation caused by proinflammatory cytokines. Using immunohistochemistry methods in the dorsal horn of a rat model of lumbar disc herniation, the authors investigated the effects of pulsed radiofrequency (PRF) current administration to the dorsal root ganglion (DRG) on pain-related behavior and activation of microglia, astrocytes, and mitogen-activated protein kinase. METHODS: A total of 33 Sprague-Dawley rats were randomly assigned to either a sham-operated group (n = 10) or a nucleus pulposus (NP)-exposed group (n = 23). Rats in the NP-exposed group were further subdivided into NP exposed with sham stimulation (NP+sham stimulation, n = 10), NP exposed with PRF (NP+PRF, n = 10), or euthanasia 10 days after NP exposure (n = 3). The DRGs in the NP+PRF rats were exposed to PRF waves (2 Hz) for 120 seconds at 45 V on postoperative Day 10. Rats were tested for mechanical allodynia 10 days after surgery and at 8 hours, 1 day, 3 days, 10 days, 20 days, and 40 days after PRF administration. Immunohistochemical staining of astrocytes (glial fibrillary acidic protein), microglia (OX-42), and phosphorylated extracellular signal-regulated kinases (pERKs) in the spinal dorsal horn was performed at 41 days after PRF administration. RESULTS: Starting at 8 hours after PRF administration, mechanical withdrawal thresholds dramatically increased; this response persisted for 40 days (p < 0.05). After PRF administration, immunohistochemical expressions of OX-42 and pERK in the spinal dorsal horn were quantitatively reduced (p < 0.05). CONCLUSIONS: Pulsed radiofrequency administration to the DRG reduced mechanical allodynia and downregulated microglia activity and pERK expression in the spinal dorsal horn of a rat model of lumbar disc herniation.

Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications-a review.

BACKGROUND: The objective of this review is to evaluate the efficacy of Pulsed Radiofrequency (PRF) treatment in chronic pain management in randomized clinical trials (RCTs) and well-designed observational studies. The physics, mechanisms of action, and biological effects are discussed to provide the scientific basis for this promising modality. METHODS: We systematically searched for clinical studies on PRF. We searched the MEDLINE (PubMed) and EMBASE database, using the free text terms: pulsed radiofrequency, radio frequency, radiation, isothermal radiofrequency, and combination of these. We classified the information in two tables, one focusing only on RCTs, and another, containing prospective studies. Date of last electronic search was 30 May 2010. The methodological quality of the presented reports was scored using the original criteria proposed by Jadad et al. FINDINGS: We found six RCTs that evaluated the efficacy of PRF, one against corticosteroid injection, one against sham intervention, and the rest against conventional RF thermocoagulation. Two trials were conducted in patients with lower back pain due to lumbar zygapophyseal joint pain, one in cervical radicular pain, one in lumbosacral radicular pain, one in trigeminal neuralgia, and another in chronic shoulder pain. CONCLUSION: From the available evidence, the use of PRF to the dorsal root ganglion in cervical radicular pain is compelling. With regards to its lumbosacral counterpart, the use of PRF cannot be similarly advocated in view of the methodological quality of the included study. PRF application to the supracapular nerve was found to be as efficacious as intra-articular corticosteroid in patients with chronic shoulder pain. The use of PRF in lumbar facet arthropathy and trigeminal neuralgia was found to be less effective than conventional RF thermocoagulation techniques.

15. Discogenic low back pain.

An estimated 40% of chronic lumbosacral spinal pain is attributed to the discus intervertebralis. Degenerative changes following loss of hydration of the nucleus pulposus lead to circumferential or radial tears within the annulus fibrosus. Annular tears within the outer annulus stimulate the ingrowth of blood vessels and accompanying nociceptors into the outer and occasionally inner annulus. Sensitization of these nociceptors by various inflammatory repair mechanisms may lead to chronic discogenic pain. The current criterion standard for diagnosing discogenic pain is pressure-controlled provocative discography using strict criteria and at least one negative control level. The strictness of criteria and the adherence to technical detail will allow an acceptable low false positive response rate. The most important determinants are the standardization of pressure stimulus by using a validated pressure monitoring device and avoiding overly high dynamic pressures by the slow injection rate of 0.05 mL/s. A positive discogram requires the reproduction of the patient's typical pain at an intensity of > 6/10 at a pressure of < 15 psi above opening pressure and at a volume less than 3.0 mL. Perhaps the most important and defendable response is the failure to confirm the discus is symptomatic by not meeting this strict criteria. Various interventional treatment strategies for chronic discogenic low back pain unresponsive to conservative care include reduction of inflammation, ablation of intradiscal nociceptors, lowering intranuclear pressure, removal of herniated nucleus, and radiofrequency ablation of the nociceptors. Unfortunately, most of these strategies do not meet the minimal criteria for a positive treatment advice. In particular, single-needle radiofrequency thermocoagulation of the discus is not recommended for patients with discogenic pain (2 B-). Interestingly, a little used procedure, radiofrequency ablation of the ramus communicans, does meet the (2 B+) level for endorsement. There is currently insufficient proof to recommend intradiscal electrothermal therapy (2 B±) and intradiscal biacuplasty (0). It is advised that ozone discolysis, nucleoplasty, and targeted disc decompression should only be performed as part of a study protocol. Future studies should include more strict inclusion criteria.

Pulsed radiofrequency: current clinical and biological literature available.

OBJECTIVE: Pulsed radiofrequency, where short bursts of radiofrequency energy are applied to nervous tissue, has been used by pain practitioners as a non- or minimally neurodestructive technique, alternative to radiofrequency heat lesions. Clinical advantages and mechanisms of this treatment remain unclear. The objective of this study was to review current clinical and laboratory data. DESIGN: We systematically searched the MEDLINE database (PubMed) and tables of contents of electronically available pain journals. Reference lists of relevant reports and international scientific pain congress abstract books were also hand searched. Only those reports on pulsed radiofrequency were withheld. RESULTS: The final analysis yielded 58 reports on the clinical use of pulsed radiofrequency in different applications: 33 full publications and 25 abstracts. We also retrieved six basic science reports, five full publications, and one abstract. CONCLUSIONS: The accumulation of these data shows that the use of pulsed radiofrequency generates an increasing interest of pain physicians for the management of a variety of pain syndromes. Although the mechanism of action has not been completely elucidated, laboratory reports suggest a genuine neurobiological phenomenon altering the pain signaling, which some have described as neuromodulatory. No side effects related to the pulsed radiofrequency technique were reported to date. Further research in the clinical and biological effects is justified.

Intradiscal high-voltage, long-duration pulsed radiofrequency for discogenic pain: a preliminary report.

BACKGROUND: Intradiscal radiofrequency, with the electrode placed in the center of the nucleus pulposus, has been a controversial procedure in patients with discogenic pain. Possibly the effect has not been due to the production of heat, but to exposure to electric fields. DESIGN: We have investigated the effect of high-voltage, long-duration intradiscal pulsed radiofrequency in patients with one-level discogenic low back pain, as confirmed by discography. OUTCOME MEASURE: The pain intensity score on a 0-10 numeric rating scale (NRS) was taken as outcome measure. PATIENTS: Eight patients were reported. The mean duration of pain was 6.3 years (range 0.5-16, median 4). The mean NRS score was 7.75 (range 5-9). Disc height was reduced 60% in one patient and up to 30% in the others. INTERVENTION: A 15-cm, 20-gauge needle with a 15-mm active tip was placed centrally in the disc. Pulsed radiofrequency was applied for 20 min at a setting of 2 x 20 ms/s and 60 V. RESULTS: There was a very significant fall in the NRS scores over the first 3 months (P < 0.0001). On an individual basis, all patients had a fall of the NRS score of at least 4 points at the 3-month follow-up. A follow-up of 12.8 months (range 6-25, median 9) was available for five patients. All these patients are now pain free, except for one patient with an NRS score of 2. Conclusion. It is concluded that this method merits a controlled, prospective study.

Pulsed radiofrequency treatment of the lumbar medial branch for facet pain: a retrospective analysis.

BACKGROUND: The use of pulsed radiofrequency (PRF) for treatment of the medial branch is controversial. STUDY DESIGN: A retrospective study of the results of PRF treatment of the medial branch in 48 patients with chronic low back pain was carried out. Patients who did not respond were offered treatment with conventional radiofrequency heat lesions. PATIENT MATERIAL: Patients were included who had low back pain and >50% pain relief following a diagnostic medial branch block. The mean age was 53.1 +/- 13.5 years, the mean duration of pain was 11.4 +/- 10.9 years (range 2-50). Nineteen patients had undergone surgery. METHODS: Pain scores on a numeric rating scale of 1-10 were noted before and after the diagnostic nerve block, before the procedure, and at 1-month and 4-month follow-up. PRF was applied for 2 minutes at a setting of 2 x 20 ms/s and 45 V at a minimum of two levels using a 22G electrode with a 5 mm active tip. Heat lesions were made at 80 degrees C for 1 minute. OUTCOME DEFINITION: A successful outcome was defined as a >60% improvement on the numeric rating scale at 4-month follow-up. RESULTS: In 21/29 nonoperated patients and 5/19 operated patients, the outcome was successful. In the unsuccessful patients who were subsequently treated with heat lesions, the success rate was 1/6. CONCLUSION: The setup of our study does not permit a comparison with the results of continuous radiofrequency (CRF) for the same procedure, other than the detection of an obvious trend. When comparing our results with various studies on CRF of the medial branch such a trend could not be found. Based on these retrospective data, prospective and randomized trials, for example, radiofrequency vs PRF are justified.

Pulsed radiofrequency for radicular pain due to a herniated intervertebral disc--an initial report.

Pulsed radiofrequency (PRF) has been used for the treatment of radicular pain, due to a herniated intervertebral disc, but so far the data are anecdotal. This is a retrospective study on 13 consecutive patients with this type of pain, at levels L3 to S1. All patients had a diagnosis confirmed by imaging, all had neurological abnormalities, and all were scheduled for surgical intervention. All 12 patients who had a profession had stopped working. Treatment consisted of application of PRF to the dorsal root ganglion of the affected segmental nerve, or in the case of S1 to the segmental nerve at the level of the S1 foramen. One patient underwent disc surgery, and one other patient underwent a spinal fusion 1 year following PRF treatment. He had no leg pain at the time of operation. The remaining patients did not require surgical intervention. The numeric rating scale (NRS) score fell from 7.83 to 2.25 over the first 2 weeks, followed by a gradual further fall to 0.27 at the final follow-up, 15.8 (11 to 23) months after the procedure. Compared with the initial NRS score the data were significant (P < 0.01) from 4 weeks after the procedure. Neurological abnormalities resolved except in one patient, who had decreased sensibility in a small area in the L3 dermatome at the last follow-up. All professionally active patients went back to work after 0.49 months (0.1 to 1). It is concluded that PRF may potentially be a viable alternative for epidural steroid injections in the treatment of acute radicular pain, due to a herniated intervertebral disc, and that further studies, including a control group, should be carried out to establish the value of this method.

Exposure of the dorsal root ganglion in rats to pulsed radiofrequency currents activates dorsal horn lamina I and II neurons.

OBJECTIVE: Application of pulsed radiofrequency (RF) currents to the dorsal ganglion has been reported to produce long-term relief of spinal pain without causing thermal ablation. The present study was undertaken to identify spinal cord neurons activated by exposure of the dorsal ganglion to pulsed RF currents in rats. METHODS: Left-sided hemilaminectomy was performed in adult Sprague-Dawley rats to expose the C6 dorsal root ganglion. An RF electrode (0.5 mm diameter) with a thermocouple for temperature monitoring was positioned on the exposed ganglion, and rats were assigned to one of three treatment groups: pulsed RF treatment (20 ms of 500-kHz RF pulses delivered at a rate of 2 Hz for 120 s to produce tissue heated to 38 degrees C), continuous RF (continuous RF currents for 120 s to produce tissue heated to 38 degrees C), or sham treatment (no RF current; electrode maintained in contact with ganglion for 120 s). RESULTS: Treatment with pulsed RF but not continuous RF was associated with a significant increase in the number of cFOS-immunoreactive neurons in the superficial laminae of the dorsal horn as observed 3 hours after treatment. CONCLUSION: Exposure of the dorsal ganglion to pulsed RF currents activates pain-processing neurons in the dorsal horn. This effect is not mediated by tissue heating.

Chronic back pain, acute postoperative pain and the activation of diffuse noxious inhibitory controls (DNIC).

The effect of the presence of either chronic or acute clinical pain on pain threshold and on the nociceptive flexion reflex (RIII) threshold was studied. The experimental pain sensation and the flexion reflex were evoked by trains of short electrical pulses. It was hypothesized that both kinds of clinical pain would be able to induce 'diffuse noxious inhibitory controls' (DNIC) and thereby raise the 2 experimental thresholds. Patients with chronic low back pain, patients with postoperative pain from oral surgery, and pain-free subjects were tested in 3 conditions: during baseline, after i.v. administration of a placebo, and after i.v. administration of naloxone. In comparison with 2 pain-free control groups, the 2 pain groups had a significantly higher pain threshold in all conditions. However, the RIII threshold was not significantly elevated in chronic or acute pain patients compared to controls. Naloxone had no effect on the RIII or pain threshold in any of the groups. It is concluded that the increased pain threshold which is frequently found in chronic pain patients, and which could be confirmed in the present study, does not result from a DNIC effect. The adaptation level theory offers an alternative explanation. Also, the acute postoperative pain in this study did not seem to induce DNIC. Because other forms of acute pain have been found to be effective in activating DNIC, future research should establish which pains are and which pains are not effective.