ASRA Pain Medicine Update

When used as a treatment for chronic pain, the primary goal behind neural ablation is to interrupt and inactivate nociceptive pathways by way of creating a thermal lesion. Ablation of neural structures is not a new technology, but the application of this process continues to evolve as we develop faster, more effective, and more accurate modes of delivery. Although neural ablation can be achieved using several modalities including cryoablation and chemical neurolysis, radiofrequency (RF) is likely used most commonly by chronic pain providers. The advantages of using RF ablation include its ability to be precise and reproducible while producing long-term, but not permanent, effects. It also provides the option to stimulate neural tissue prior to ablating, thereby confirming desired target proximity while avoiding possible undesirable targets. 

Both conventional radiofrequency and pulsed radiofrequency interventions are valuable and effective tools used to treat chronic pain, but they should be considered only when conservative measures have failed.

RF waves comprise the lowest part of the continuous electromagnetic spectrum, bound by the frequencies 3 Hz to 300 GHz.^[1] In the procedural setting, the RF ablation needle tip acts as a cathode of an electrical circuit, which is closed by a dispersing pad placed elsewhere on the body. The electrode itself, however, does not heat up and is not hot to touch — much like a microwave does not “heat up.” The electrode generates an alternating electromagnetic field that sets nearby molecules (mostly water) into motion. Energy lost between these molecules results in a temperature increase, which becomes the source of heat that is then transmitted farther by tissue connectivity.^[1] While the small cross-sectional area of the needle tip creates a very high surrounding energy flux, the large cross-sectional area of the grounding pad disperses the current into a much smaller flux of energy. As a result, the thermal ablation is limited to the tissue closest to the needle tip. 

Conventional radiofrequency (CRF) and pulsed radiofrequency (PRF) are two available forms of RF technology commonly used in clinical practice. While CRF applies a continuous current of electricity that heats tissues to neurodestructive temperatures of 60-80°C, PRF employs short bursts of current resulting in lower maximum temperatures of 40-42°C.^[2] Tissue death at various temperatures are shown in Table 1. The latent periods between bursts allow heat to dissipate so that neurodestructive temperatures are not reached. Although they use similar technology, research has shown that these two forms of ablation use two different mechanisms of action.^[3],[4]

Table 1: Time until tissue death when exposed to various temperatures.^[7]

Conventional Radiofrequency

The goal of CRF is to create a thermal lesion large enough to encompass the target structures while also avoiding critical ones (without creating premature desiccation). This can only be accomplished by optimizing tissue connectivity, duration of ablation, and cathode size. Although tissue connectivity allows for the propagation of radio waves and the subsequent enlargement of the thermal lesion, it can also be a limiting factor. If the power is increased too quickly, tissues closest to the electrode become desiccated or charred as cells and their contents vaporize.^[1] Charred tissue can no longer transmit electrical or thermal energy, thereby acting as an insulator, limiting any additional extension of desired tissue destruction. Thus, thermal lesion size can be optimized by gradually heating tissues to 60-80°C for 75-185 seconds generated through an electromagnetic field with a frequency of 250 kHz.^[5],[6]

Cathode size, or the length of the needle’s active tip, also plays an important role in determining the overall lesion size and shape. Whereas smaller gauge needles will create wider lesions, longer active tips will result in longer and more ovoid-shaped lesions. Commonly used instruments include 17-22-gauge RF needles with active tips ranging between 4-10 mm in size. 

Targeting neural structures can be challenging, even with the use of fluoroscopy. For this reason, a larger thermal lesion is frequently desired. Methods to accomplish this include:

• Employing a smaller gauge cathode
• Utilizing a deployable dual- or V-shaped needle tip (which increases the size of the active tip without having to increase needle gauge)
• Using internally cooled electrodes that enhance slow heating of adjacent tissues, resulting in less charring and greater tissue conductivity
• Performing multiple ablations^[1],[7],[8]

Once RF needle placement is confirmed by fluoroscopy, sensory and motor stimulation can be performed to assess its proximity to the target nerve. First, optimum sensory stimulation may be achieved at 50 Hz by gradually increasing voltage until pain or sensation is appreciated that is comparable to usual/targeted pain.^[9] Thresholds between 0.3-0.9 V are generally correlated with an appropriate distance to sensory fibers while stimulation appreciated < 0.2 V may represent intraneural needle placement.^[9] Subsequent stimulation of motor fibers can be performed at 2 Hz using an approximate range of 1-10 V. Voltage is gradually increased to 1.5-2 times the intensity required to elicit previous sensory symptoms.^[10] Distal muscle contractions in the face, upper extremity, or lower extremity indicate that the needle tip is near a spinal nerve and requires adjustment.^[11]

The prolonged high temperatures employed by CRF cause coagulative necrosis to both cellular and acellular structures.^[12] Histologically, both axonal degeneration and collagen fiber destruction of endo-, peri-, and epi-neurium structures occurs.^[13],[14] Based on the prolonged length of functional loss and damage to the nerve, CRF produces a third- or fourth-degree injury consistent with Wallerian degeneration and is associated with the potential for neuroma formation. Functional, but not complete, re-innervation of the site usually occurs over a period of months to years.^[15],[16] This typically corresponds to a return in patient’s pain. 

Pulsed Radiofrequency

Often presented as a less destructive alternative to CRF, PRF describes a different application of RF technology in which a 500 kHz current is applied for 2 pulses per second, with each pulse lasting 20 msec. Although transient endoneurial edema can occur, studies have shown a return to normal morphology by 7 days post-treatment.^[14],[16] This supports the conclusion that destruction of neural elements is not thought to be the mechanism of action of PRF. Some studies have implied that PRF alters gene expression, neuronal membrane function, and cytokine regulation.^[4],[13] Although the true mechanism remains unclear, it’s been postulated that the temporary electromagnetic field created by PRF results in cellular change that favorably alters the transmission of pain signals. In any case, the effects of PRF do not fit into the Sunderland’s scale of 5 degrees of nerve damage,^[15] and additional studies are required to better understand its mechanism.  

The advantages of PRF when compared to CRF are that it is significantly less painful, causes less destruction of tissues, and doesn’t have the inherent risks of possible neuroma formation or deafferentation pain.^[18] The disadvantage to PRF is that it provides a shorter duration of pain relief for patients, requiring the procedure to be repeated more frequently. The ongoing challenge associated with the mainstream use of PRF is the relative lack of randomized controlled trials supporting its efficacy. For future research, there is a distinct need for high-quality randomized controlled trials that can help identify optimal parameters and proper nerve targets for the application of PRF in clinical practice. 

Limitations

Whether using CRF or PRF ablation, it is also important to remember that the lesions they create are relatively small compared to their neural targets and that they do not selectively destroy only nociceptive fibers. Thus, accurate placement of RF needles is paramount and requires a thorough knowledge of the target neural tissues and their associated radiographic landmarks. Complications associated with RF are usually mild and well tolerated, but they can include neuroma formation, deafferentation pain, and dysesthesia. Lastly, it should be noted that the pain relief RF provides is temporary, and thus repeat procedures should be considered and discussed as a part of the initial treatment plan.

Conclusion

Both CRF and PRF interventions are valuable and effective tools used to treat chronic pain, but they should be considered only when conservative measures have failed. Although additional research is essential in determining the growing utility of RF, it currently has many applications in treating chronic pain. Therefore, it is important to educate patients and physicians about RF as an alternative and effective therapeutic option for treating chronic pain. 

References

1. Organ LW. Electrophysiologic principles of radiofrequency lesion making. Appl Neurophysiol. 1976;39(2):69-76. https://doi.org/10.1159/000102478
2. Vanneste T, Van Lantschoot A, Van Boxem K, Van Zundert J. Pulsed radiofrequency in chronic pain. Curr Opin Anaesthesiol. 2017;30(5):577-82. https://doi.org/10.1097/ACO.0000000000000502
3. Tun K, Cemil B, Gurcay AG, et al. Ultrastructural evaluation of pulsed radiofrequency and conventional radiofrequency lesions in rat sciatic nerve. Surg Neurol. 2009;72(5):496-500.
4. Van Zundert J, de Louw AJ, Joosten EA, et al. Pulsed and continuous radiofrequency current adjacent to the cervical dorsal root ganglion of the rat induces late cellular activity in the dorsal horn. Anesthesiology. 2005;102(1):125-31.
5. Lord SM, Bogduk N. Radiofrequency procedures in chronic pain. Best Pract Res Clin Anaesthesiol. 2002;16(4):597-617. https://doi.org/10.1053/bean.2002.0250
6. Gupta A, Huettner DP, Dukewich M. Comparative effectiveness review of cooled versus pulsed radiofrequency ablation for the treatment of knee osteoarthritis: a systematic review. Pain Physician. 2017;20(3):155-71. 
7. Hong K, Georgiades C. Radiofrequency ablation: mechanism of action and devices. J Vasc Interv Radiol. 2010;21(8 Suppl):S179-86. https://doi.org/10.1016/j.jvir.2010.04.008
8. Kapural L, Mekhail N. Radiofrequency ablation control for chronic pain control. Curr Pain Headache Rep. 2001;5(6):517-25. https://doi.org/10.1007/s11916-001-0069-z
9. Koning MV, Koning NJ, Koning HM, van Kleef M. Relationship between sensory stimulation and side effects in percutaneous radiofrequency treatment of the trigeminal ganglion. Pain Pract. 2014;14(7):581-7. https://doi.org/10.1111/papr.12124
10. Markman D, Hadian P, Philip A. Diagnosis and treatment of facet-mediated chronic low back pain. In: Smith H. Current Therapy in Pain. Philadelphia, PA: Saunders; 2009.
11. Orhurhu V, Urits I, Orman S, Viswanath O, Abd-Elsayed A. A systematic review of radiofrequency treatment of the ankle for the management of chronic foot and ankle pain. Curr Pain Headache Rep. 2019;23(1):4. https://doi.org/10.1007/s11916-019-0745-5
12. Hayashi K, Thabit G, Massa KL, et al. The effect of thermal heating on the length and histologic properties of the glenohumeral joint capsule. Am J Sports Med. 1997;25(1):107-12. https://doi.org/10.1177/036354659702500121
13. Choi S, Choi HJ, Cheong Y, Lim Y-J, Park H-K. Internal-specific morphological analysis of sciatic nerve fibers in a radiofrequency induced animal neuropathic pain model. PLoS One. 2013;8(9):e73913. https://doi.org/10.1371/journal.pone.0073913
14. Podhajsky RJ, Sekiguchi Y, Kikuchi S, Myers RR. The histologic effects of pulsed and continuous radiofrequency lesions at 42 degrees C to rat dorsal root ganglion and sciatic nerve. Spine (Phila Pa 1976). 2005;30(9):1008-13. https://doi.org/10.1097/01.brs.0000161005.31398.58
15. Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain. 1951;74(4):491-516. https://doi.org/10.1093/brain/74.4.491
16. Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review. Neurosurg Focus. 2004;16(5):E1. https://doi.org/10.3171/foc.2004.16.5.2
17. Vallejo R, Tilley DM, Williams J, Labak S, Aliaga L, Benyamin RM. Pulsed radiofrequency modulates pain regulatory gene expression along the nociceptive pathway. Pain Physician. 2013;16(5):E601-13. 
18. Pangarkar S, Miedema ML. Pulsed versus conventional radio frequency ablation for lumbar facet joint dysfunction. Curr Phys Med Rehabil Rep. 2014;2:61-5. https://doi.org/10.1007/s40141-013-0040-z