BIPOLAR PULSED MODE RADIOFREQUENCY IN SPINE AND PERIPHERAL NERVES SURGERIES

Author: Munir Ahmad Elias M.D., Ph.D.
Prof. in neurosurgery and human neurophysiology.
Jordan-Amman
26-January-2019

ABSTRACT
BACKGROUND AND PURPOSE: Pain management is an integral part in the surgery of the spine, in particular the lumbar, cervical spine and peripheral nerves with radicular pain due to prolapsed lumbar, cervical disk, stenosis, spondylolisthesis, kyphoscoliosis or other conditions. Thermal mode radiofrequency cannot be applied to the major roots or nerves, since it will cause thermal damage to them, which have very important function for locomotion. Thermal mode radiofrequency after several trails proved to be ineffective in treating the radicular pain. It only destroys the branches supplying the facets, which play a minor role in pain generation. Bipolar pulsed mode radiofrequency applied directly to the exposed roots, nerves or spinal cord will not damage them and give pain relief and improve the conductivity of the neural structures.
MATERIALS AND METHODS:
Bipolar pulsed mode radiofrequency was started to be used in our practice since 22-August-2015 up to today. During this period we performed 173 surgeries applying this technique. The patients were not informed, that such procedure will be applied to them during surgery, to eliminate possible psychological factors, except one patient. Using MultiGen Stryker Radiofrequency Generator, motor evaluation followed by a bipolar pulsed mode with temperature 42 Celsius, 2Hz 20 msec bursts for 240 sec. was applied using the curved catheters above and below the axilla of the roots, the major nerves and spinal cord location of interest. Motor response was evaluated after the procedure. Some patients received such a procedure for one root, others up to 12 roots, depending at the clinical picture and nature of the surgery. Only one patient was informed about the procedure because it was required to be cooperative to evaluate the brachial plexus function.
RESULTS: 173 patients with 1988 roots exposed to this procedure were retrospectively analyzed for the possible damage from such procedure, or the effectiveness of ameliorating the radicular or neuralgia pain after surgery. Since the nerve was exposed during surgery, it was studied morphologically and with inspection, there was no apparent morphological changes. All the patients showed dramatic functional improvement as result of root decompression. This in other words, reflect the fact, that BPRF will not affect the root function if applied properly, instead it will improve its conductivity. All the patients after surgery, forgot the sciatic pain, but instead the wound pain took precedence, since before application of such procedure the patients were complaining of both. The patient with post-inflammatory neuralgia of the right brachial plexus showed immediate disappearance of the agonizing pain and improvement of most of the involved nerves.
CONCLUSIONS: We recommend using bipolar pulsed mode radiofrequency to every exposed root, nerve or spinal cord segment involved around the pathology during surgery, to jump to new level of treatment optimization. Decompression of the compressed or stretched neural elements, whatever the type of surgery, then elimination of pain generators by BPRF with certain improvement of the function of root or nerve and spinal cord.

ABBREVIATIONS: BPRF Bipolar Pulsed mode radiofrequency; VAS Visual Analog Scale;

Keywords: Spine surgery, Peripheral nerve surgery, Bipolar pulsed mode radiofrequency, thermal mode radiofrequency, radiculopathy, facet pain, sciatica, neuralgia.  

Spine and peripheral nerves surgeries represent more than 82% of the surgical activity of the neurosurgeons and new specialty in the last 20 years founded as spine surgery as a separate specialty. Minor group of orthopedic surgeon came to the field and most of the neurosurgeons continued their activity in this profile. It is clear that spine surgery in general is the most popular and the most important part to avoid catastrophic events such as paraplegia, quadriplegia and other neurologic deficits.
Most of the technical advancements were directed to improve the instrumentation and visualization with endoscopic or minimally invasive surgery and intraoperative navigation. Hundreds of manufacturers were involved in improving the metallic constructs of various devices to have less complications and low profile design. Others for pain management went with very expensive stimulators with rechargeable batteries with long-term stimulation to fool the pain pathways. The last technologies have their complications and their high cost limit their implication in the daily practice. Destructive surgeries using thermal mode radiofrequency have their limitations and negative consequences and can be considered as salvage type of procedures with poor results.
Ninety nine percent of the patients with spine and peripheral nerves pathologies come to medical facilities due to pain. Most of them even do not notice their neurological deficit, until they undergo neurological evaluation. Pain is the major component of their pathology. In some cases, even after correction of the morphologic cause of pain, the patients continue to suffer of pain, especially when the pain was for long time before surgery. If the root was irritated and compressed before surgery, then after decompression, the root becoming lax but the pain fibers still irritated in most cases after then.
MultiGen Stryker was applied in intention to use it for back pain with thermal coagulation, which proved to be inferior in expectations and led to coagulation of the facet innervation and was abandoned. The bipolar pulsed mode was included in the protocol and with hesitance was applied to the roots during open surgery of the spine. Taking into consideration of the works of Omar Pasha ⁷ with his excellent results in obtaining pain relief by using his own modified epidural catheter and the works of Cahana A et al ¹ and Sluijter M.E ⁹, they put the theoretical background to selective damage of the nociceptive fibers of the roots by exposing them to bipolar radiofrequency for 240 sec with 2 Hz, 20 msec pulse duration with 05-1 watt source.

The first case was performed 22-August-2015 and the last in this group in 23-January-2019. 173 cases were operated using this procedure. The patients were intentionally not informed about the procedure to avoid psychological, socioeconomic, cultural and several factors except one patient with agonizing neuralgia of the right brachial plexus.

The patients age ranged from 21 up to 82 years  with median age 52.7 years. 36 patients with spondylolisthesis with scoliotic deformity, one patient with huge meningioma at C1-2-3 level and one patient with post-inflammatory agonizing neuralgia of the right brachial plexus. The others were with lumbar and cervical prolapsed disci or recurrent disci of the lumbar spine or discitis with osteomyelitis of the lumbar area.

Using MultiGen Stryker, motor stimulation was applied to the involved root or nerve before exposing it to the bipolar pulsed mode with default of 2 Hz, 20 msec duration with temperature 42 Celsius and catheters bended end 10 mm distal exposed tip one applied to the medial and the other to the lateral wall of the root trying to be near the ganglion at the first 22 cases, then to any level of the root or nerve, the root was exposed for 240 seconds. It was necessary to let blood accumulate or put some saline to fulfill the exposed shaft of the catheters, otherwise they will not function. Some of the roots were severely damaged due to severe compression, necessitating their dural repair by 6 zero nylon and they were after then exposed to the procedure. After that another motor stimulation was performed to the same nerves or roots for comparison.

In one case with huge intradural meningioma at C1-2-3 the protocol of BPRF was applied to the involved roots at the right side to include the spinal cord. The patient showed acceptable motor spinal cord and radicular response after manipulation, but progressed deep right sided paralysis after surgery. The patient came walking with excellent functional recovery 2 weeks after surgery. This case confirming that the procedure is not harming even the spinal cord, but confirming that the postoperative paraplegia is transitory and promote affected spinal cord and emerging roots recovery.

In cases 114-169 we intentionally applied another protocol. The roots were exposed to motor stimulation and recorded the minimal voltage, required to obtain the response, then waiting 4 minutes, we repeated the motor stimulation second time and recorded the minimal voltage. BPRF was applied to the involved roots for 4 minutes and we performed the third motor response. The data confirmed that the roots are improving even before application of BPRF. It can be explained by the fact that the root after decompression, regaining less or more normal conditions, such as the CSF around the root below the axilla regain its normal anatomical relation and the axoplasma inside the compressed fibers start to flow downward. The curve of improvement after BPRF took not a linear improvement, but with better than expected results, which means that the procedure was playing a positive added role in the process of root recovery. These data led to the following conclusions:
1. Decompression by itself promote recovery by several factors.
2. Repetitive stimulation at different intervals promote recovery as therapeutic effect.
3. BPRF also add the degree of recovery by ameliorating the tiny non-myelinated fibers, which are responsible for pain generation, promoting the improvement of function of the other fibers. 

RESULTS

Dilemma in Evaluation
The procedure was part of the surgical intervention, and at first series, it was difficult to guess if the improvement of the patient was due to the surgery alone or to the added procedure. For sure the data telling that no harm from the procedure was detected if the procedure was performed properly, instead the motor conductivity improved in all cases at variable degree. The author have experience for 37 years in spine and peripheral nerves surgeries and most of the patients had gratifying results. The procedure was added to minimize the sciatica pain after surgery. There was a notice with this group of patients that their sciatica was minimal or less in comparison to the previous patients, and they noted the wound pain. This could be explained that the patients without this procedure had both sciatica and wound pain after surgery and when the sciatica became less, they started to notice their wound pain.

Pain scaling
There are several scaling paradigms to evaluate the pain, such as the VAS and other schemes are not reliable, since the people are differently react with pain and the psychological  and many different factors, make pain assessment is difficult to digitize and to make comparison between 2 different groups. To eliminate most of these factors, we intentionally did not inform all the patients that such procedure will be applied to them during surgery except one patient.  

What to do to get the results
The author used his long-standing experience in spine and peripheral nerves surgeries and personally led the questionnaire with indirect hints to evaluate the pain and followed the patients behavior after surgery and after discharge with outpatient follow up. The procedure was introduced to minimize the annoying postoperative complains of the patients, Considerable difference was noted about the sciatic, radicular or neuralgia pain. In some of the patients the sciatica completely disappeared, most decreased to at least 90% and some claim pain in the hip , shoulder areas and down to the ankles. Most of them noticed numbness of the previously painful areas, which is a usual finding before applying BPRF. Others noticed escalation of pain in the contralateral side, necessitating to change the strategy of the operative protocol in the future patients. 

Limitations of the study
The study now is more established than before. It still needs huge material with complications to see how the patients will react and how long the efficacy of the procedure will remain. It is still not known how the unmyelinated fibers regenerate and the poorly myelinated group responsible to to nociceptive sensation. At least the immediate postoperative period was gratifying for this period of study.

Complications related to the study
One patient after performing motor stimulation, somebody by mistake put the parameters to one side for thermal mode bipolar radiofrequency with 80 degrees Celsius. It was noted after 40 seconds and the application was stopped. The parameters then were corrected and the patient was routinely sent to the ward. The wound was oozing for 4 days, for what revision of the wound was performed. There was a tiny burn of the dura under the axilla with CSF coming from below this point. Several stitches were applied to this area using 6 zero prolyn, after what the CSF leak stopped, despite the fact that there was no apparent dural defect or tear. The patient was put in anti-Reverse Trendelenburg position with Valsalva maneuver to check for CSF leak. No CSF leak. For more security a piece of muscle and Surgicele were applied over the suspected area. There is a new phenomenon that there is delayed CSF leak which was not present during surgery, but taking place several days after surgery. Three cases were observed among the 173 cases where BPRF was applied. The common sign among them, that the motor stimulation was very high reaching above 6V. This fact, confirming that the affected root was severely anatomically damaged before surgery and despite the fact we use bipolar stimulation, we must with caution elevate the threshold of stimulation above 5.5V to avoid thermal damage to the involved dural sheet of the root. It could be that the effect of such event causing the appearance of such dural tear several days after the surgery.

Complications not related to the study
One patient showed severe rejection reaction to the allograft, which manifested itself by severe LBP without sciatica with severe elevation of CRP and ESR, for what removal of the allograft was performed 4 days after the first surgery. From the procedure in this 173 group there was one complication. Despite the motor conductivity of 99% of the roots improved and 1% remained the same.

DISCUSSION

The study, even limited with short time and patients number, but it became clear that BPRF applied to the exposed roots, nerves and spinal cord during spine and peripheral nerves surgeries is effective and showing noticeable reduction of sciatic, radicular, and neuralgia pain in the operated population without having any side effects. The importance of such procedure that it practically bring the outcome of most of spine surgeries to a new better level. Decompressive procedures, foraminotomy removal of the extruded disc, correction of the scoliotic deformity, fusion of the pathologic overmobile segment of the spine, insertion of artificial disc, reduction of the dislocated segments , intradural extramedullary tumor resection, and many procedures evolved the last 115 years jumped with spine and peripheral nerves surgeries and all of them are mechanical. They could provide improvement of the neural function through mechanical decompression and realignment to more or less acceptable position, but they did not resolve the problem of the neuropathic and nociceptive fibers of the roots, which sometimes even escalate in pain generation after putting them from the pathologic to more or less acceptable position. Here come the importance of this procedure, that ameliorate this pathologic firing of pain, taking the patient to better postoperative outcome. The patient is not worried if that his foot, leg, arm regaining power, if he is suffering from pain. He will be pleased if the pain disappear.

Drop foot still remaining unresolved problem, but application of BPRF with motor stimulation before and after the procedure showed new information: If the root is responding to currents less than 4V before the procedure and improving to 3-2 V after, then recovery of the drop foot is for sure anticipated. If the motor response is more than 4.5 V or the response is in the contralateral root and the motor response is the same, even with slight improvement, but over 4.5 V, then recovery is unlikely will be, but the agonizing pain disappears. Trail to use PRP to promote recovery of the damaged nerve is questionable, even not effective.

Application of BPRF in redo surgery for discitis yielded acceptable results, concerning the radicular pain. Pain due to inflammation of the lumbar muscles remain unresolved since the etiology of pain is slightly different and it is not purely neurogenic.

MultiGen cannot not help when gross anatomical compression was applied to the root in early recurrence of the disc. It seems that, the pain transmission take over other fibers, beside the C- and unmyelinated fibers, as in this case.

Application of BPRF to a normal nerve, will not change the motor conductivity threshold. This was noticed in several cases, such as in the case performed 25-January-2017 at the left L4 root.

In surgery for recurrent disc, it was noticed that the motor response of the exposed root from the scar require higher volts to obtain response, but keeping below 3 V. After application, the motor response require lower voltage in all cases with considerable disappearance of radicular pain and dramatic improvement of the function of the nerve. In one case with missed piece of recurrent extruded disc of L4-5 with far right upward migration, the patient was not complaining of typical sciatica, instead pain in the right buttock. MRI the next day after the first surgery showed this missed piece, which was completely separated from the extrusion and compressing the right L4 root for which foraminotomy was performed, causing the root to be more mobile and generating agonizing in the right buttock, not with walking, but when lying in the right side. Removal of this missed fragment resolved his agonizing pain and he was discharged 26-January-2017. This case a demonstration that even with application of BPRF to the root, if organic lesion still persisting, then an atypical pain will take precedence.

In some cases there was contralateral root response, but to lesser degree as in this case.

In other rare cases the motor response was higher in voltage after BPRF application with slight difference, but the patients usually showed dramatic improvement as in this case. It could be explained with slight shift of the electrodes during performance of BPRF, or other not known to me factors. It could be that the nerve is recovering minute by minute after decompression and this can explain why the motor conductivity is improving after the BPRF application, which require 4 minute session.

Concerning the cervical and dorsal spine, the procedure was directed to the roots posteriorly if the surgery was from the posterior approach. In case of anterior approach the electrodes were directed parallel to disc space to catch the roots after emergence from the canal, but before crossing the vertebral arteries. In some cases it was possible to achieve this goal from within the disc space lateral edges. But this require a bended electrode around 90 degrees tip and sometimes it is difficult to achieve it due to narrow angles. 

Omar Omar-Pasha had material of 1000 cases published 11 years ago. We used his experience with configuring the parameters which he found optimal: 1 to 0.5 watt, 42 Celsius, 2 Hz 20 msec peak duration for 240 seconds duration of pulsed mode radiofrequency exposure of the root. These parameters could be needing more correction with more correction of the catheters localization and positioning. This is the work of the neurohistologists, physists and manufacturers.

The main trend is to provide the patient the better outcome, avoiding destructive procedures, or at least destroying the pathologically annoying structures selectively with preservation of the functionally important fibers with in the neural tissue. In retrospective analysis, the function of the manipulated nerve, root or even spinal cord improved dramatically.

Monopolar Pulsed RF

While making a radiofrequency lesion in the standard thermal RF mode, the tissue which surrounds the tip of the electrode is exposed to a concentrated electric field that induces tissue heating. The electric field (E-field) intensity decreases precipitously with distance from the tip, falling to a low level at distances beyond the extent of a typical heat lesion (Cosman and Cosman 2005). Since the high temperatures within the heat lesion volume reliably induce cellular death, it is assumed that the E-field per se has little or no clinical effect in thermal RF.
The introduction of pulsed RF (Sluijter et al. 1998) was motivated by the desire to expose nerves to high electric fields without gross neurodestructive heating, so as to reduce the risk of RF treatment in sensitive anatomy such as the DRG. In the mid-1990s, Cosman and Sluijter modified a standard lesion generator to deliver radiofrequency voltage bursts at a repetition rate of 2 Hz. Since each burst is only 20 ms long, the intervening inactive period 480 ms allows heat to dissipate into the surrounding tissue after exposure to the electric field (Figs-1 and 2).

Fig-1: Pulsed RF. Red arrow indicates the target point to detect L5 medial branch.

Fig-2: Schematic RF waveforms for CRF and PRF (parameters and times not to scale).

As such, the RF voltage, and thus the E-field strength, can be increased while holding the electrode tip temperature at or below 42 °C, a level assumed not to produce gross neurodestructive effects (Fig-3).

Fig-3: Schematic E-field patterns. Bottom: E calculated in tissue for a 22-electrode at V(RF)=45 V.

Cosman and Cosman (2005) have shown that tissue around the electrode shaft is broadly exposed to high-intensity E-fields without substantial heating. They also showed that the very intense electric fields at electrode’s pointed tip cause “hot flashes” during each RF burst. Some salient points are:
• Ahead of the tip: Within ≈0.2 mm of the electrode point, temperature spikes into the neurolytic range and above the measured tip temperature during each burst of RF (Fig-4).

Fig-4: E-and T-fields during the first PRF for V(RF)=45 V and pulse width =20ms.

At larger distances and between RF bursts, the temperature does not substantially exceed that of the electrode tip. While the electric field is maximal within ≈ 0.2 mm of the electrode point, it falls off very quickly with distance ahead of the tip so that beyond ≈0.2 mm, its magnitude is smaller ahead of the tip than it is lateral to the shaft (Fig-5).

Fig-5: Hot flashes during a PRF pulse.

• Around the shaft: Temperature does not substantially exceed the measured tip temperature. The electric field falls off slowly with distance and exposes tissue to electrical forces that are high in biological terms and that appear to produce a disruptive effect (Erdine et al. 2009); as such, its range of influence is broader around the shaft than ahead of the tip (Figs.5 and 6).

Fig-6: E-fields dominate over T-fields in PRF. The opposite is true for CRF.

In typical pulsed RF practice, the generator is set to target pulse voltage = 45 V, pulse width = 20 ms, and pulse rate = 2 Hz. The generator then automatically adjusts the either the pulse voltage, the pulse width, or less commonly the pulse rate to maintain the temperature at or below 42 °C for 120 s. Sluijter further recommends that the tissue impedance be reduced by the injection of about 1 ml of local anesthetic or normal saline. This is an approach supported by finite-element calculations of the electric field that assume directional saline spread toward the nerve.
The clinical effects and pain-relief mechanism of pulsed RF is the subject of ongoing scientific investigation. Though there is growing evidence that pulsed RF has a physical effect on nerves, in the absence of an established model of PRF’s pain-relief mechanism, what is known about pulsed RF’s pain-relief efficacy depends on clinical trials using specific parameters and control algorithms. Since the first publication about the clinical use of pulsed RF in pain management, numerous peer-reviewed clinical studies of pulsed RF technique and pain-relief outcomes have been published, including an RCT related to PRF treatment of cervical radicular pain (Van Zundert et al.¹¹ 2007).
While treatment parameters vary somewhat, these published clinical trials generally use set values voltage = 45 V, pulse width = 20 ms, pulse rate = 2 Hz, and treatment time = 120 s, and they all use delivery algorithms that vary either the pulse voltage or the pulse width to maintain the temperature at or below 42 °C. Beyond this, a number of questions about pulsed RF methodology remain unanswered: Is it better to approach a nerve “ side - on ” or “ point - on ” with a PRF electrode ?
Many clinicians prefer to use the point-on/perpendicular approach as they feel this allow for more precise targeting, with greater electric field effect. While this may be valid, since the E-field is very large only within a very small distance ahead of the electrode point (≈0.2 mm), and otherwise falls to intensities less than those around the electrode shaft, it is unlikely that the very large E-field at the electrode point accounts for the full clinical effect. Further, since the E-field at the point has destructive intensity and is coincident with high-temperature hot flashes, the point- on approach cannot be having a purely nondestructive effect. On the other hand, since the E-field intensity declines less precipitously lateral to the electrode shaft, the side-on/parallel approach exposes a larger nerve volume to elevated electric fields, with less heating. Recent
animal studies by Erdine et al. (2009) show that the side-on approach can disrupt axonal microtubules, microfilaments, and mitochondria. Clinical trials are required to determine the relative efficacy of the side-on and point-on methods.
Can clinical outcomes be improved by changing the typical set values ?
Voltage = 45 V, pulse width = 20 ms, pulse rate = 2 Hz, and treatment time = 120 s?
These parameters were selected for practical purposes by PRF’s inventors, and there is no clinical evidence that they are “ideal” in any sense. Many workers use longer treatment times in excess of 4 min, or pulse width = 10 ms and pulse rate = 4 Hz, as they feel it augments the electric field exposure, also known as E-dose (Cosman and Cosman 2005). While these variations may prove useful, there is currently no clinical proof that any such variations improve outcomes.
Do clinical outcome vary depending on the temperature control algorithm ?
Most RF generators implicitly incorporate at least one method of PRF temperature control that varies either pulse voltage, pulse width, or pulse rate, while fixing the other parameters. For example, the NeuroTherm NT 1100 generator’s promotional literature refers to its particular pulse-rate algorithm by the trade name pulse dose. The Cosman G4 generator incorporates an E-dose setting that allows the operator to select between control algorithms to adjust a nerve’s exposure to the E-field. While all clinical studies showing positive PRF outcomes to date employ generators that vary either the voltage or the pulse width to control temperature, they do not compare these control methods. The authors are not aware of any clinical study of PRF outcomes in which temperature is controlled by varying the pulse rate or using pulse dose. There is theoretical reason to believe that pulse-rate/pulse-dose algorithms may be less effective if PRF’s mechanism depends on longterm depression (LTD). The LTD hypothesis of PRF pain relief was proposed by Cosman and Cosman (2005) and is based on the idea that PRF stimulates action potentials and thus subthreshold postsynaptic potentials at 2 Hz, which falls within a rate range known to induce LTD using conditioning stimulation. Since a pulse-rate/pulse-dose algorithm may reduce the pulse rate substantially below the known LTD range, it may also reduce the LTD effect. Voltage and pulse-width control algorithms do not suffer from this concern. Nevertheless, in the absence of strong model of PRF’s mode of action or clinical trials, PRF temperature control algorithms cannot be clinically distinguished.

Physical Properties of PRF in Pain Modulation

There are two output modes of RF generators that are used today to produce pain relief. The first is the standard, thermal RF mode which uses a continuous sinusoidal waveform RF output, commonly referred to as continuous RF or CRF. The second uses a series of pulsed bursts of RF signal, referred to as pulsed RF or PRF. The amplitude, V(RF), of both these waveforms is measured in units of voltage (V). For voltages commonly used in clinical practice, a continuous RF waveform produces a heat lesion. This means that the neural tissue near the uninsulated, metal electrode tip is heated continuously to destructive temperatures (greater than 45–50 °C) by ionic friction of the RF currents in the tissue. Thus, the CRF lesion volume includes all tissue within the 45–50 °C isotherm boundary, which tends to have an ellipsoidal shape that encompasses the electrode tip. Within this lesion volume, all cell structures are macroscopically destroyed by heat. The action of pulsed RF on neural tissue is different. Because the RF output is delivered in bursts of short duration relative to the intervening quiescent periods, the average temperature of the tissue near the electrode is not raised continuously or as high as for continuous RF at the same RF voltage. Since the PRF voltage is typically regulated to keep the average tip temperature in a nondestructive range, other mechanisms produce the clinically observed pain-relieving effects.
The electric field, E, is the fundamental physical quantity that governs all the actions of RF output on neural tissue, both for pulsed RF and for continuous RF modes. The electric field is created in space around an RF electrode that is connected to the output voltage V(RF) from an RF generator. E is represented by an arrow (vector) at every point in space around the electrode tip, indicative of the magnitude and the direction the force it will produce on charged structures and ions in the tissue. The E-lines indicate the pattern of E in a homogeneous medium. The E-field produces various effects on tissue including oscillations of charges, ionic currents, charge polarizations, membrane voltages, and structure-modifying forces. For continuous RF mode, the dominant consequence of these effects is the production of heat in the tissue caused by frictional energy loss due to the ionic currents that are driven by the E-field. However, for pulsed RF, the effects of E-field are more complex and varied and range from heat flashes, to modification of neuron ultrastructure, to neural excitation phenomena. All of these effects can play a role in neuronal modification, though exactly how they produce antinociception in PRF treatments is an area of active scientific investigation.
To understand any of the E-field effects of pulsed RF, the magnitude of the E-field around an actual electrode in tissue must be determined. This has been calculated for a typical electrode during a PRF pulse using finite- element computational methods (Cosman and Cosman). The quantitative values of E and temperature T at distances from the electrode tip are plotted for a 22 Gauge electrode at V(RF) = 45 V. Near the sharp point of the electrode, the E-field has strength of up to 187,000 V/m. This drops off rapidly with distance from the point. At the side of the electrode, E is 46,740 V/m and drops off more slowly with lateral distance. These are very high E-fields in biological terms and are capable of a variety of modifications of neurons that account for the effects of pulsed RF.
Two consequences of these predictions are supported by experimental and clinical observations. The first is that, as a consequence of the very high E-fields at the
electrode tip, there are hot flashes at the electrode tip that can be thermally destructive to neurons. The second is that there are significant nonthermal effects of the E-field on neurons at positions away from the point of the tip that are certainly related to the pain-relieving effects of PRF.
During the brief RF pulse, a hot spot occurs at the tip which can be 15–20 °C above the average tissue temperature of the tissue that remains near body temperature of 37–42 °C. This has been confirmed by ex vivo measurements and finite-element calculations. The intense E-field and hot flashes could be expected to have destructive effects on neural tissue very near the tip point. Evidence for such destruction has been observed in vitro (Cahana et al.). This may play a role in PRF’s clinical effect when electrode point is in the nerve or pressing against the nerve. However, it is unlikely that such focal effects can account for all of PRF pain relief, since the region of extremely high E-fields and T hot flashes are likely confined to less than about 0.2 mm radius from the electrode point.
There is evidence that direct, nonthermal effects are important in PRF. It is known that pain relief can be achieved when the side of the electrode tip, not the tip point, is next to an axon or DRG. While the hot flash fluctuations are less than 1 °C at 0.5 mm from the tip in any direction for typical PRF voltages, at lateral distances of greater than 1 mm, the magnitude of the electric field is still large in biological terms. For example, finite-element computation of the E-field for V(RF) = 45 V predict that the E is 20,000 V/m at 0.5 mm and 12,000 V/m at 1.0 mm laterally. Thus, neuronal modifications in this E-field range should be significant.

Comparison of E and T strengths between typical CRF and PRF waveforms shows striking differences between these RF modes. Calculations predict that after 60 s of CRF at V(RF) = 20 V, E = 21,000 V/m and T = 60–65 °C at the lateral tip surface and E = 2,750 V/m and T = 50 °C at 1.8 mm away. In contrast, after 60 s of PRF with V(RF) = 45 V, E = 46,740 V/m and T = 42 °C at the lateral tip surface and E = 6,100 V/m and T = 38 °C at 1.8 mm away. In other words, in PRF, the direct electric field effects are more prominent, whereas in CRF, the thermal fields are more prominent and largely mask the E-field effects.
Combined with the understanding that PRF has a clinical effect even when the electrode is not placed on the nerve directly, these physical observations suggest that the E-field is directly involved in the analgesic effect of PRF. It is known that PRF E-fields produce significant transmembrane potentials on the neuron membrane and organelles (Cosman and Cosman 2005). The E-field can also penetrate the membranes of axon and the DRG soma to disrupt essential cellular substructures and functions. For example, PRF applied to the DRG of rabbits causes pronounced neuron ultrastructural modifications that are seen only under electron microscopy (Erdine et al. 2005) and that are likely to modify or disable the cell’s function. Additionally, PRF applied to afferent axons in
the rat sciatic nerve with a “parallel”/“side-on” approach causes disruption of microtubules, microfilaments, and mitochondria; the disruption appears to be more pronounced in C fibers than in A-delta and A-beta fibers (Erdine et al. 2009). This would suggest that PRF can produce subcellular, microscopic lesions on neurons in a volume around the electrode, possibly resulting in reduction of afferent pain signals. Blockage of axonal transmission of action potentials has been observed in the sural and sciatic nerves of rats using electrophysiological microelectrode recording on individual teased nerve fibers (Cosman et al. 2009); the blockage occurs at lower voltages for a “perpendicular”/“point-on” approach than it does for a “parallel”/“side-on” approach, likely due to the very high E-field and hot flashes present at the electrode’s pointed tip. PRF membrane potentials are also capable of neural excitations (action potentials) by a process called membrane rectification. This excitation has been observed in the sural and sciatic nerves of rats using the aforementioned teased-fiber recording technique (Cosman et al. 2009). Because the PRF pulse rate is similar to that of classical conditioning stimulation (1–2 Hz), it has been proposed that PRF may have a similar action (Cosman and Cosman 2005). Conditioning stimulation is capable of suppressing synaptic efficiency of A-delta and C-fiber afferent nociception signals (Sandkuhler et. al. ⁸), a phenomenon known as long-term depression (LTD). Therefore, the PRF might be reducing transmission of pain information by LTD of synaptic connections in the dorsal horn. The appropriate exposure of PRF for a given pain syndrome and anatomical target, for either microscopic or LTD mechanisms, should be governed by the PRF “E-dose” (Cosman and Cosman 2005). E-dose provides a parametric measure of E-field strength and integral pulse/time exposure.

Histo-morphological effects of CRF and PRF

Cosman et. al.² have shown that pulsed RF (PRF) exposes tissue to higher electric field (E-field) intensities than does continuous/thermal RF (CRF). For a CRF heat lesion with tip temperature 65 °C, the E-field strength is 21,000 V/m around the needle, as compared to 46,740 V/m for a PRF lesion with tip temperature 42 °C. At a lateral distance from the shaft roughly coincident with the outer limit of the CRF heat lesion, the CRF E-field strength is 2,700 V/m, whereas the PRF E-field strength is 6,100 V/m. Furthermore, since PRF produces lower temperatures around the shaft, the tissue that would be exposed to neurolytic temperatures in the CRF case is principally exposed to high E-fields in the PRF case. The E-field strength is highest within ≈ 0.2 mm of the pointed needle tip; transient, focal, high-temperature spikes are also present during each RF pulse at this location. On the other hand, since the E-field intensity decreases less precipitously around the shaft than ahead of the tip, it has a higher intensity over a larger range around the shaft than it does directly ahead of the tip.
In the light of all the recent work on pulsed radiofrequency, many workers prefer to use the needle tip (“perpendicular approach”) as they feel that this approach allows for more precise targeting. They feel that use of the needle tip combines a reduced heat effect with a greater electric force effect and therefore carries with it a theoretically reduced risk of neuritis than would use of the needle shaft. There is, however, no scientific evidence for this hypothesis!
Sluijter et. al⁶ describes four phases in a pulsed radiofrequency procedure, viz.:
• A stunning phase, which provides immediate relief.
• A phase of postprocedure discomfort, which may last for up to 3 weeks.
• A phase of beneficial clinical effect, which is of variable duration.
• A phase of recurrence of pain; we are still in the early days but many cases record 4–24 months of relief.
There is no clinical evidence of any nerve damage with pulsed radiofrequency. Higuchi et al. (2002) have presented experimental evidence that pulsed radiofrequency applied to the rat cervical dorsal root ganglion causes upregulation of the immediate early gene c-fos [ 4 ].
With the technological improvements made during the last decade, cellular and ultrastructural effects of PRF and RF have been better evaluated.
Pulsed radiofrequency does seem to have a clinical effect on peripheral nerves. Some pointing out the lack of laboratory evidence for this phenomenon and felt that this may be due to changes induced in the function of the Schwann cells.
Cahana et al.¹ have shown that pulsed radiofrequency affects cell cultures only within a range of 1 mm, raising questions as to how close to the target tissue one needs to be with the electrode. Podhajsky et al. (2005) compared histologic effects of CRF, PRF, and continuous heat at 42 °C on DRG and sciatic nerves 2, 7, and 21 days after procedure. PRF did not induce any paralysis or sensory deficits in animals. Only mild edema and some fibroblast activation (collagen deposition in epineural space and subperineural region) around nerve fibers were seen in the PRF group at 2 and 7 days after procedure in sciatic nerve and DRG. At 21 days after PRF, these mild changes were back to normal. CRF group showed extensive edema, swollen axons and degeneration of neurons. Erdine et al.³ reported an animal study showing PRF induced in DRG neurons only, an enlargement of endoplasmic reticulum, and a mild increase of vacuoles. RF showed at the same level mitochondria degeneration, loss of integrity of nuclear membrane, and highly increased number of vacuoles in the DRG cells [ 8 ]. These two studies led to the conclusion PRF does not appear to rely on thermal injury to achieve its clinical effect.
One year later, Hamann et al.⁴ applied pulsed radiofrequency to the sciatic nerve or the L5 dorsal root ganglion in the rat. They studied, at up to 14 days after application, the expression of activating transmission factor 3 (ATF3), an early intermediate gene expressed in response to cell stress. They found that ATF3 was upregulated selectively in the small cells of the dorsal root ganglion after direct application to the ganglion but not after application to the sciatic cells. They concluded that pulsed radiofrequency selectively stresses the population containing the nociceptor cell bodies. It would also appear that the primary effect of pulsed radiofrequency is predominantly on the cell body rather than on its processes. The observation that PRF targets preferentially neurons whose axons are composed of small diameters (A-delta and C fibers) was also reported by in this study.
It is only in 2009 that publication started reporting more precise neuronal modulation at the ultrastructural level after PRF. Tun et al.⁹ confirmed by ultrastructural approach that CRF (70 °C), as opposed to PRF (42 °C, 120 s, was responsible for much more neurodestruction in the sciatic nerve. Erdine et al. published interesting results on electronic microscopy of sensory nociceptive axons showing physical evidence of ultrastructural damage following PRF. The mitochondria, microtubules, and microfilaments showed various degrees of damage and disruption. These damages were more important in C fibers than A-delta than A-beta fibers. This observation was consistent with the clinical effect of PRF which seems to have greater effects on the smaller pain-carrying C- and A-delta fibers. Protasoni et al.⁶ also reported some mild effects of PRF on DRGs at the acute phase of exposure. At light microscopy (LM) few differences appeared after PRF, but at transmission electron microscopy (TEM), myelinated axons appeared delaminated and the organization in bundles was lost. Also, T gangliar cells contained abnormal smooth reticulum with enlarged cisternae and numerous vacuoles.
As a conclusion authors said PRF slightly damages myelin envelops of nerve fibers at acute stage. No information came out of this study on long-term effect to know whether or not these effects were persistent or just transient.
Pulsed radiofrequency may be useful where conventional RF is contraindicated, e.g., neuropathic pain, and it is safe in locations where conventional RF may be potentially hazardous, e.g., DRG lesioning. PRF is mostly a neuro-remodeling technique based on neuromodulation as opposed to RF which is mainly based on neurodegeneration to reach its clinical effects. PRF is virtually painless as no heat is generated.

Bipolar Pulsed Mode Radiofrequency versus Thermal Mode
We intentionally used the thermal coagulation mode for back pain without using corticosteroids and minimal amount of Xylocain and found that at best the patients mentioning improvement around 10%, others at all. It became clear that this setup is useful for facet pain, which is a very minor contributor to pain generation. We stopped this application and keeping it for very limited indications. It cannot be used for major roots which are the major contributors of pain. Here come the importance of bipolar pulsed mode radiofrequency, which selectively destroy the pain fibers, which are small unmyelinated or tiny A1-delta fibers responsible for nociceptive sensation. The application of BPRF gave at worst more than 90% benefit without making harm to the postoperative neural recovery, instead the nerve motor conductivity immediately improved after the procedure.

Suggestions to improve the technology and the postoperative results
1. The current setup is based in MultiGen which can simultaneously apply the stimulation for 2 roots. This setup take around 8-10 minute to achieve. If the patient needs 12 roots to be treated a 60 min time at best is needed to complete the task for the 12 roots. It will be a welcome if such apparatus can produce such treatment with at least 4-6 channel treatment to minimize the duration of the treatment plan.
2. Since the sensory part of the fibers are dorsally located and the root is exposed,  it is better to have reusable catheter-electrode with a tip having a semicircular configuration to circumscribe the root from above, to provide better contact with nerve and selectively the sensory part.
3. The next group was exposed to 2 level bipolar BPRF. The upper level will be at the proximal part of the axilla and the lower level below the DRG. We will use a 10 mm length elastic tube cut longitudinally and the 4 catheters fixed to corners. This will provide proper contact to the root structures and accumulate more structures to the BPRF effect. With accumulation of the material, it became clear that it is not important to target the DRG.
4. If distraction is planned during spondylolisthesis or scoliosis, it is better to apply motor response before and after distraction. In case that deterioration of the motor conductivity after distraction was noticed, the surgeon must decrease the distraction and inspect the root and repeat the motor response until it becomes as before distraction, then apply the BPRF. This will eliminate the postoperative clinical deterioration, which can be seen in certain cases.

CONCLUSIONS
After this study, the application of BPRF to the exposed roots, nerves and spinal cord during spine and peripheral nerves surgeries became a routine part of surgery. Even when expected that the patient could suffer from the other side of surgery, such as after distraction correction, some of suspected roots were exposed and the BPRF was applied to them to avoid unwanted possible postoperative pain in the contralateral side. The procedure is simple and harmless and yielding better postoperative course after spine and peripheral nerves surgeries.

REFERENCES
1. Cahana A, Vutskits L. Muller D. Acute differential modulation of synaptic transmission and cell survival during exposure to to pulsed and continuous radiofrequency energy. Journal of Pain 2003;4: 179-202
2. Cosman Jr ER, Cosman Sr ER. Electric and thermal field effects in tissue around radiofrequency electrodes. Pain Med. 2005;6(6):405–24.
3. Erdine S, Bilir A, Cosman ER, Cosman ER. Ultrastructural changes in axons following exposure to pulsed radiofrequency fields. Pain Pract. 2009;9(6):407–17.
4. Hamann W, Abou-Sherif S, Thompson S, Hall S. Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons. Eur J Pain. 2006;10:171–6.
5. Higuchi Y, Nashold BS, Sluijter M, Cosman E, Pearlstein R. Exposure of the dorsal root ganglion in rats to pulsed radiofrequency currents activates dorsal horn lamina I and II neurons. Neurosurgery. 2002;50(4):850–6.
6. Protasoni M, Reguzzoni M, Sangiorgi S, Reverberi C, Borsani E, Rodella LF, Dario A, Tomei G, Dell’Orbo C. Pulsed radiofrequency effects on the lumbar ganglion of the rat dorsal root: a morphological light and transmission electron microscopy study at acute stage. Eur Spine J. 2009;
18:473–8.
7. Omar Omar-Pasha Application of Pulsed Radio Frequency to the Dorsal Horn and Dorsal Roots. www.omar-pasha.de
8. Sandkuhler J, Chen JG, Cheng G, Randic M. Low frequency stimulation of the afferent A-delta fibers induces long-term depression at the primary afferent synapses with substantia gelatinosa neurons in the rat. J Neurosci. 1997;17:6483–91.
9. Sluijter M.E., van Kleef M. Characteristics and mode of action of radiofrequency lesions. Current Reviews on Pain 1998; 2: 143-150.
10. Tun K, Cemil B, Gurhan A, Kaptanoglu E, Sargon MF, Tekdemir I, Comert A, Kanpolat Y. Ultrastructural evaluation of pulsed radiofrequency and conventional radiofrequency lesions in rat sciatic nerve. Surg Neurol. 2009;72:496–501.
11. Van Zundert J, Patijn J, Kessels A, Lamé I, van Suijlekom H, van Kleef M. Pulsed radiofrequency adjacent to the cervical dorsal root ganglion in chronic cervical radicular pain: a double blind sham controlled randomized clinical trial. Pain. 2007;127(1–2):173–82.

Notice: This article will be revised periodically with accumulation of surgical data.
Last revision: 26-January-2019