Pulsed Radiofrequency

The use of radiofrequency (RF) electrical currents to create quantifiable and predictable thermal lesions has been practiced since the 1950s. The first reported use of RF in the treatment of intractable pain appeared in the early 1970s, which involved the use of conventional radiofrequency current (CRF) to create thermal lesions. The CRF lesions for pain control are created by the passage of RF currents through an electrode positioned adjacent to a pain pathway in order to interrupt the nociceptive impulses and provide the needed pain relief. Application of RF current imparts energy to the tissues surrounding the electrode tip, raising the local tissue temperature while the electrode is heated passively. The RF current is switched off once the desired tissue temperature is reached, and repetition of this cycle maintains the selected temperature. Temperatures above 45°C have been known to be neurodestructive, though the time required to achieve neurolysis decreases in conjunction with rising temperatures. Even though selective destruction of unmyelinated C and A-delta fibers has been suggested at lower temperatures, further studies showed that all nerve fiber types were damaged equally during thermal RF application. Hence, during CRF application tissue, temperatures selected are typically above the neurodestructive range but below the point of gas formation—typically from 65°C to a maximum temperature of 80°C–90°C. In order to avoid motor nerve damage causing weakness, and worsening pain secondary to local neuritis, neuroma formation, and deafferentation pain, the use of high-temperature CRF is generally reserved for nonneuropathic pain (e.g., facet joint, sacroiliac joint, and knee arthritis), whereby the target nerves do not contain motor fibers or carry nonpain sensory information. In order to avoid these complications, lower temperatures in the range of 55°C–70°C were arbitrarily selected in a study of CRF application to the dorsal root ganglia (DRG). In another study evaluating DRG lesioning, no difference in clinical results was found between CRF lesions created at 40°C or 67°C. The authors of the latter study hypothesized that the electrical currents rather than temperature resulted in this outcome. This observation generated immense interest, as the risks of weakness and deafferentation pain could theoretically be obviated, and the indications for RF broadened immensely, by the use of lower temperatures.

Pulsed radiofrequency (PRF) was introduced to maximize the delivery of electrical currents by the use of higher voltages, while the risk of thermal tissue injury was concomitantly minimized by maintaining the tissue temperatures well below the neurodestructive range—below 42°C. Because the use of CRF inevitably results in nerve damage (i.e., neuroma), and nerve damage is a requisite for neuropathic pain, the use of PRF is primarily limited to neuropathic pain states. The conflicting goals of PRF, high voltage, and nonneurodestructive temperatures are achieved by applying the RF currents in a pulsatile manner, allowing time for the heat to dissipate in between RF pulses. By using mathematical calculations, the authors showed that the high-density electrical currents generated at the electrode tip could stress the cellular membranes and cause altered cellular function and cell injury. Later investigators suggested a combined role of electrical and thermal tissue injury from PRF application. They ascertained that the slow response time of temperature measuring devices used during PRF may not reliably exclude the possibility of brief temperature spikes causing thermal tissue injury. Laboratory studies have shown neuronal activation, cellular stress, and cellular substructure damage after PRF application. However, other experimental studies show that the observed cellular injury from PRF application is predominantly a function of thermal injury, thereby undermining the role of electrical currents. Although the exact mechanism of PRF application remains unclear, there is a growing body of evidence in the form of randomized controlled preclinical and clinical trials that suggests it may be efficacious in individuals with neuropathic pain.

PRF is applied similar to CRF by placing an electrode in the vicinity of the target nociceptive nerve. Although the orientation and size of the electrical field affected by PRF is similar to CRF, whether or not the electrode should be placed parallel to the nerve or at a different orientation is not known. During classic PRF application, RF currents are applied for 20 milliseconds, at 2 Hertz, for a total duration of 120 seconds. Thus for the majority of lesioning duration (480/500 milliseconds) no RF current is applied. The voltage is controlled in a manner such that the maximum electrode temperature achieved remains below 42°C. Variations from this PRF protocol have been infrequent, with the exception of longer treatment duration. PRF has been applied for 4, 8, and 20 minutes by some investigators, and there is evidence from preclinical and clinical studies that longer treatment cycles may be associated with increased effectiveness.

Water-Cooled Radiofrequency

Water-cooled radiofrequency (WCRF) ablation has been in clinical use for some time, used primarily in cardiac electrophysiology and for tumor ablation ; however, its use in pain medicine is fairly recent. The basic principle of WCRF application is similar to CRF application: A thermal lesion is created by placing an electrode in the vicinity of a target neural structure. However, WCRF is applied by using a specialized multichannel electrode that is actively cooled by continuous flow of water at ambient temperature ( Fig. 68.1 ). The active cooling prevents the electrode from acquiring the high surrounding tissue temperature and allows the continued flow of current and consequent heating of a larger tissue volume, thus creating a larger thermal lesion. The WCRF thermal lesion is composed of a few millimeters of cooled tissue immediately surrounding the electrode, followed by spherical isotherms of increasing tissue temperature that are surrounded by lower temperature isotherms ( Fig. 68.2 ). Similar to the CRF lesion size, the size of lesion created by WCRF application depends on the probe size, electrode temperature, and duration of current applied. If a 60°C isotherm is used as the measure for the lesion’s peripheral extension, a 17-gauge electrode with a 4-mm active tip, and an electrode set temperature of raised to 55°C–60°C for 150 seconds achieves adjacent tissue temperatures of >80°C and would create a thermal lesion of 8–10 mm in diameter. Even though a spherical area of tissue heating is expected, several factors influence the symmetry of the WCRF lesion in vivo. Active heat sinks, such as cerebrospinal fluid and blood, which are present in the thecal sac and epidural venous plexus, respectively, and passive heat-sinks, such as osseous and muscular spinal structures, help determine the eventual shape and size of the thermal lesion.

Multichannel water-cooled electrode.

Courtesy Halyard Health Inc.

Morphology of water-cooled radiofrequency lesion.

Courtesy Halyard Health Inc.

A larger area of tissue damage with WCRF application increases the probability of successful denervation of a pain generator with numerous and/or variable nociceptive innervation. The clinical use of WCRF in pain medicine employed two distinct forms of WCRF techniques, monopolar and bipolar lesioning, limited primarily to the treatment of sacroiliac joint dysfunction (SJD) and discogenic pain (DP), respectively. Additional studies are emerging however on the use for treating chronic knee pain. For the treatment of SJD unipolar WCRF is applied to the L5 dorsal ramus and S1, S2, S3, and sometimes S4 lateral branches, which range in number from 1 to 4, and three monopolar lesions are created lateral to each respective sacral foramen ( Fig. 68.3 ). Using a 17-gauge specialized electrode with a 4-mm active tip, the RF current is applied for 150 seconds with a set temperature of 60°C. The set temperature of 60°C creates adjacent tissue temperatures >80°C. Due to the larger anticipated lesion size, the introducer needle is typically kept at a “safe distance” from the sacral nerve roots—8–10 mm from the lateral edge of posterior sacral foramen. To avoid injury to the segmental spinal nerve, WCRF is generally not applied to the L5 dorsal ramus, and CRF is used instead. For the treatment of DP, bipolar WCRF is applied to the posterior-lateral disc annulus by placing two 17-gauge introducer needles and specialized RF electrodes ( Fig. 68.4 ). The electrode temperature is raised to 55°C over 11 minutes, and this temperature is maintained for an additional 4 minutes.

Water-cooled radiofrequency application for discogenic pain.

Courtesy Halyard Health Inc.

Cryoprobe needle.

Cryoneurolysis

Cryogenic nerve injury is not generally associated with neuroma formation, hyperalgesia, and deafferentation pain, attributes typical of neuronal injury caused by other physical modalities such as surgical nerve sectioning, thermal RF lesioning, or chemical neurolysis. Trendelenburg first demonstrated that freezing of peripheral nerves caused nerve disruption without the risk of neuroma formation. Later, Carter et al. and Beazley et al. showed that the peripheral nerve injury from extreme cold caused axonal and myelin sheath disintegration and lead to Wallerian nerve degeneration, without disruption of endoneurium, perineurium, and epineurium. The mechanism of cryogenic nerve injury appears to emanate from damage to the vasa nervorum, resulting in endoneural edema, increased endoneural pressure, and consequent axonal disintegration. Autoimmune response triggered by the release of sequestered neural elements has also been implicated in the long-term effects of cryoablation. The spared connective elements and Schwann cell basal laminae provide ready substrate for nerve regeneration from intact proximal axons. The axonal regeneration typically occurs at a rate of about 1–1.5 mm/week, and the duration of analgesia from cryoablation consequently depends on the time taken by the proximal axons to reinnervate the end organs, typically ranging from weeks to months.

Although the local anesthetic-like properties of cold have been known since ancient Egyptian times, tissue temperatures must be lowered to critical levels for adequate duration in order for the disintegrative nerve changes to occur—a distinction analogous to the difference between cold and numb fingers and frostbite. The critical temperature required to cause such disintegrative nerve changes has been shown to be minus 20°C. In addition, the degree and the duration of analgesia is proportional to the severity of the cryogenic nerve damage. It is therefore crucial that the tissue temperatures are maintained below the critical levels for an adequate duration during cryolesioning. The extent of freezing and the likelihood of the target nerve injury therefore depend on the probe size, probe proximity to the target nerve, freezing duration, and number of freeze cycles applied. Repeat freeze and thaw cycles increase the size of the eventual ice ball formed.

The first cryoneedle, developed in 1962, used liquid nitrogen as the refrigerant and lowered the needle tip temperature below minus 196°C. In 1967, the currently used cryoprobe needle (see Figs. 68.4 and 68.5 ) was developed, using the Joule-Thompson enclosed gas expansion principle and lowering the probe tip temperature to between −ve 50° and −ve 70°C. The contemporary cryoprobe is a double lumen aluminum tube that connects to a gas source by flexible tubing, and either nitrous oxide or carbon dioxide is delivered at a pressure of approximately 42 kg/cm ² (600 lb/in ² —psi) to the inner cryoprobe lumen. The gas under pressure escapes through a small orifice from the inner lumen near the cryoprobe tip and returns to the console through the outer cryoprobe lumen. The drastic drop in the pressure at the probe tip—from 600–800 psi to 10–15 psi—allows gas expansion and consequent cooling. Heat absorbed from the tissues surrounding the probe tip lowers the temperature and creates an ice ball around the probe tip. Currently available cryoprobe sizes include a 14-gauge (2-mm) probe that roughly forms a 5.5-mm ice ball, and an 18-gauge (1.4-mm) probe that forms a 3.5-mm ice ball.

Schematic design of cryoprobe needle.

Meticulous localization of the target nerve is necessary to increase the likelihood of nerve disruption. Most currently used cryoprobes are therefore equipped with a built-in nerve stimulator function that allows both motor (2 Hz) and sensory (100 Hz) testing. The probe also has a thermistor incorporated in the tip to precisely monitor the target tissue temperatures. The console unit is equipped with nerve stimulator controls and temperature and gas pressure gauges, and has a gas regulator switch that allows precise control of gas flow. To ensure safe and effective cryoablation, gas flow must be precisely regulated—inadequate gas flow is ineffective in lowering tissue temperatures below critical levels, while excessive gas flow may lead to tissue freezing proximally along the probe length and cause unintended freeze lesions such as skin burns. The cryoprobe should be withdrawn only after the ice ball has thawed, since withdrawing the probe with the ice ball still present may cause local tissue injury and avulsion of a nerve segment. The use of an introducer, such as a large gauge intravenous catheter, is often recommended during cryoprobe placement. A sharp introducer tip facilitates the placement of the less rigid cryoprobe and affords additional skin protection during cryolesioning of the superficial nerves. Typically, a 12-gauge intravenous catheter is used for the 2.0-mm probe, and a 14- to 16-gauge catheter is used for the 1.4-mm probe.

Pulsed Radiofrequency

Even though PRF has been employed in the clinical practice fairly recently, its use is relatively widespread, and it is used for both painful and some nonpainful conditions. The growing popularity of PRF is likely due to its perceived safety and clinical efficacy, particularly for neuropathic pain. PRF should be considered when further injury to the nerve(s) should be avoided in patients predisposed to neuropathic pain, while thermal RF (ablation) should be a choice for mechanical pain (e.g., facet joint, SI joint, knee arthritis). PRF has been applied to the DRG at all spinal levels in the treatment of multiple pain syndromes, including radicular pain (RP) from a herniated disc, postherpetic neuralgia, postamputation stump pain, occipital neuralgia, and inguinal herniorrhaphy pain. It is applied to a range of peripheral nerves for multiple pain syndromes such as suprascapular nerve (SSN) for shoulder pain, intercostal nerves for postsurgical thoracic pain, lateral femoral cutaneous nerve for meralgia paresthetica, pudendal nerve for pudendal neuralgia, dorsal penile nerves for premature ejaculation, splanchnic nerves for chronic benign pancreatic pain, sciatic nerve for phantom limb pain, obturator and femoral nerves for hip pain, glossopharyngeal nerve for glossopharyngeal neuralgia, occipital nerve(s) for occipital neuralgia, and genitofemoral, ilioinguinal, and iliohypogastric nerves for groin pain and orchialgia. It has also been applied to various peripheral and autonomic ganglia, including the gasserian ganglion (GG) for trigeminal neuralgia (TN); sphenopalatine ganglion for head, neck, and facial pain; and to the lumbar sympathetic chain in the treatment of complex regional pain syndrome. In some reports the target neural structure for PRF application is unclear, such as myofascial trigger points for myofascial pain, scar neuromas for postsurgical scar pain, spermatic cord for testicular pain, and intraarticularly for arthrogenic pain.

Water-Cooled Radiofrequency

The use of WCRF is currently limited to pain syndromes where the pain generator is considered to have numerous and variable sources of innervation. WCRF is used mainly for the treatment of SJD and DP. However, due to its ability to accurately deliver thermal energy to larger tissue volumes, WCRF may be effective when more traditional forms of neuroablation have failed, and its use may be extended to other pain syndromes.

Cryoneurolysis

The reported use of cryoablation in the literature is most prevalent for the treatment of postthoracotomy pain. Cryolesioning for this clinical indication is typically performed intraoperatively under direct vision, on individual intercostal nerves in the intercostal grove. All the intercostal nerves likely involved in mediating a patient’s pain, from 1 to 2 segments above the upper limit of the incision to 1 to 2 below the lower limit of the incision or the chest drain, are typically treated. The cryoablation experience with postthoracotomy pain led to its use for other chronic pain conditions of the chest wall, such as postoperative neuroma formation, costochondritis, postherpetic neuralgia, and rib fractures. In the head, neck, and facial region, cryolesioning of several regional nerves have been reported in multiple studies. The nerves included were inferior alveolar, mental, lingual, buccal, inferior dental, auriculotemporal, supraorbital, and infraorbital nerves. The painful head, neck, and facial conditions treated with cryoablation included TN, postherpetic neuralgia, atypical facial pain, and various postsurgical neuralgias. In the majority of these studies, the craniofacial nerves were exposed by open dissection for cryolesioning. In a few studies, the cryoprobe was placed using a closed technique, either percutaneously or transmucosally. There is one study evaluating cryoablation in posttonsillectomy patients, where the exact targeted neural structure was less clear. Cryoablation has also been used for the treatment of spinal and extremity pain. Its use is reported frequently for the treatment of lumbar facet syndrome (FS), where it is applied to the lumbar MBs. For extremity pain, it is used in the intermetatarsal space for the treatment of Morton’s neuroma. Cryolesioning of the ulnar, median, sural, occipital, palmar branch of the median, and digital nerves has been performed for traumatic nerve injuries and carpal tunnel syndrome. Cryoablation has also been used for the treatment of several painful conditions involving the abdomen, pelvis, and perineum. The most frequent application in this region has been for the treatment of postinguinal herniorrhaphy pain, where it is applied to iliohypogastric and ilioinguinal nerves. It has been applied to the lower sacral nerve roots for intractable perineal pain, to ilioinguinal and iliohypogastric nerves for corresponding neuralgiform chronic abdominal pain, and to the ganglion impar for intractable rectal pain. Its use has been described in many forms for pregnancy-related and postpartum pain in women. These include cryolesioning of the ilioinguinal nerve for late pregnancy abdominal pain, application to the sacral extradural canal for severe postpartum sacrococcygeal pain, and to the symphysis pubis for pregnancy-associated symphysis pubis diastasis pelvic pain. Cryolesioning of the iliac crest has also been performed for donor site pain.

Pulsed Radiofrequency

Radicular Pain

There are five trials of PRF application to the affected DRG for RP ( Table 68.1 ): four in the lumbar and one in the cervical region. The first trial of PRF use by Sluijter et al. reported its efficacy in a group of 36 patients with RP, comparing it with CRF at 42°C at 6 weeks. This trial was limited by its size, vaguely described study population, lack of adequate randomization and blinding, inadequate outcome measures (only patient satisfaction scores were used), absence of long-term follow-up, and lack of a placebo group. It also compared PRF with nonstandard CRF (CRF at 42°C), which is not routinely used in clinical practice. A trial consisting of 76 patients with lumbar RP compared PRF with combined PRF and CRF applied with the DRG, and reported no advantage of adding CRF. This trial used a nonconventional form of CRF, applying current to a maximum tolerated temperature that created a burning sensation extending from the low back to the foot; the average temperature was 54°C for 60 seconds. One trial performed in 100 patients with back pain, with or without RP, compared PRF/DRG with electroacupuncture and conservative treatment, reporting relative efficacy of the PRF treatment. This trial contained significant limitations that included a poorly defined study population, no description of the number and level(s) of DRG treated, no diagnostic nerve blocks performed prior to the DRG treatment, nonstandard treatment in the control group, poor description of blinding and randomization techniques, and the assessment of only short-term results. There are two randomized, double-blinded trials comparing PRF/DRG with sham treatment—one in the cervical and one in the lumbar region. Even though these two trials were reasonably well-conducted, both were small in size and reported only modest, short-term efficacy relative to the placebo. Currently, there is only little support of PRF/DRG for the treatment of RP in the literature.

TABLE 68.1

Controlled Trials of Pulsed Radiofrequency for Radicular Pain

Study	Methodology	Outcomes	Analysis and Limitations
1998 Sluijter et al.	Nonrandomized controlled trial 36 patients with chronic RP compared PRF with CRF at 42°C	Reported efficacy of PRF at 6 weeks compared with CRF at 42°C. Authors concluded PRF was an effective treatment modality.	Small size (36 patients) Vague study population No randomization or blinding No pain scores, used only patient satisfaction Short-term results at 6 weeks No placebo group Compared PRF to thermal RF at 42°C, which is not routinely used in clinical practice
2008 Simopoulos et al.	RCT 76 patients with lumbar RP, 37 had PRF of DRG, 39 had combined PRF and CRF (maximally tolerated temperatures)	Similar decline in VAS scores between the 2 groups at 2 months. Similar loss of analgesic effect between 2 and 4 months and return of pain to baseline by 8 months. Authors reported PRF of DRG was safe and resulted in short-term benefit; addition of CRF did not offer added benefit.	Use of nonconventional form of thermal RF not routinely practiced. Thermal RF to maximum tolerated temperature that created a burning sensation in low back to the foot. Average temperatures was 54°C for 60 s.
2010 Lin et al.	RCT 100 patients with back pain with or without RP. Compared PRF to DRG with electroacupuncture and conservative treatment.	Reported relative efficacy of the PRF treatment compared to electroacupuncture and conservative treatment	Inadequately defined study population. No description of number and levels of DRG treated. No prior diagnostic nerve blocks performed. Unknown nature of the treatments provided in conservatively treated group. Inadequate description of blinding or randomization techniques. Only short-term results reported.
2014 Shanthanna et al.	RCT, DB, PCT 32 patients with LRP	No difference between PRF and sham treatment at 3 months	Small trial—32 patients Short-term results—3 months
2007 Van Zundert et al.	RCT, DB, PCT 23 patients with cervical RP, 11 had PRF at one level DRG, 12 had ST	Significant improvement reported in 9/11 (82%) patients in the PRF group and in 4/12 GPE (33%) and 3/12 VAS (25%) in the ST group.	This study provides evidence of short-term efficacy of PRF for cervical radicular pain. Limitations: Small size—23 patients Short-term results—3 months

 

Overall Efficacy of PRF for Radicular Pain Summary:

5trials of PRF-DRG use for RP.

Overall: Either small in size, reported short-term results, and/or compared PRF to unconventional treatments.

Potential efficacy of PRF-DRF for radicular pain essentially unknown.

AU, Analgesic usage; CRF, conventional radiofrequency; DB, double-blinded; DRG, dorsal root ganglia; GPE, global perceived effect; PCT, placebo controlled trial; PRF, pulsed radiofrequency; PSS, patient satisfaction scale; RCT, randomized controlled trial; RP, radicular pain; ST, Sham treatment; TN, trigeminal neuralgia; VAS, visual analogue scale.

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