COMMENTARY
Neuroinflammatory effects of radiofrequency Accepted for publication 9 September 2013 doi:10.1002/j.1532-2149.2013.00418.x
In this issue, you will find a paper by Choi et al. (2014), entitled ‘Inflammatory responses and morphological changes of radiofrequency-induced rat sciatic nerve fibers.’ The paper describes a preclinical study comparing the anatomical and biological effects of radiofrequency treatment on the sciatic nerve of rats using clinically relevant continuous and pulsed mode protocols. Much has been written about the clinical utility of both techniques and there is a great divide among practitioners regarding the value of pulsed mode radiofrequency treatment for appropriate chronic pain conditions. In the United States, many interventional pain physicians may eschew the use of pulsed radiofrequency because of lack of reimbursement from medical insurance companies compounded by mostly poorly designed or under-powered clinical studies (Bogduk, 2006). Proponents of the pulsed mode laud the potential safety benefits of avoiding high-temperature coagulation of nervous tissue as occurs with continuous mode, theoretically limiting adverse side effects and permitting application of radiofrequency electrical current delivery to treat pain emanating from peripheral nerves with important motor functions as well (Sluijter and van Kleef, 2007). The study by Choi et al., in this issue, adds to the mounting preclinical evidence that pulsed radiofrequency produces quantifiable anatomical and functional effects on nerve function. While there are many other studies that have documented alterations in cellular structure and/or function after both types of radiofrequency protocols, this study is important in that it adds further evidence that (1) although both pulsed and continuous radiofrequency treatments produce alterations in neuroanatomy, disruption of cellular structure is much more severe and persistent after continuous than pulsed delivery of radiofrequency electrical current to the nerve; and (2) the degree and duration of anatomical effects produced by the two distinct types of radiofrequency protocols are paralleled by proportionate levels of immune cell activation and proinflammatory cytokine elaboration in the spinal cord. A logical interpretation of these results © 2014 European Pain Federation - EFIC®
is that high-temperature coagulative lesioning of peripheral nervous tissue, as occurs during continuous radiofrequency treatment, leads to a sustained, proinflammatory immune response in the spinal cord that is much diminished in amplitude and duration if pulsed mode is utilized. The extolled safety virtues of pulsed compared with continuous radiofrequency treatment can be measured as both a reduction in motor complications and a reduction in the incidence of deafferentation syndrome (although it has yet to be documented in a head-to-head comparison of both techniques). This study provides further preclinical justification for both propositions, and some of the first evidence that peripheral continuous radiofrequency lesions initiate a robust and sustained glial inflammatory response in the central nervous system. The latter observations are particularly important. Glial activation and cytokine elaboration have recently been implicated as playing pivotal roles in many animal models of chronic pain, most particularly following peripheral nerve injury (Watkins et al., 2007). The activation of this particular proinflammatory and ‘pro-pain’ mechanism by continuous radiofrequency may appear at first glance to be counterintuitive and contrary to the purpose of radiofrequency treatments for chronic pain conditions in general. However, this may be one potential explanation of paradoxical increases in pain seen in patients after radiofrequency treatments. The clinical effect of continuous radiofrequency treatment may therefore reflect a balance between analgesia produced by deafferentation-induced reduction in nociceptive input to the central nervous system and stimulation of proinflammatory, pronociceptive glial activation in the central nervous system as a consequence of deafferentation. Clinical experience indicates that analgesia is more commonly the result; however, central immunemediated inflammation may predominate in patients who experience an increase in pain following the procedure. It is important to note that in this study, no prior intervention was performed to the animals; therefore, the described effects are on naïve animals Eur J Pain 18 (2014) 149–150
149
Commentary
with no iatrogenic nervous system pathology. Whether a similar activation occurs after application of radiofrequency current to injured nerves and if only injury to specific nerves is required for central immune activation is unknown. Given prior preclinical studies of pulsed radiofrequency treatment, documentation of identifiable neural pathology, albeit largely reversible, and limited spinal immune activation as Choi et al. did in this study is not surprising. The exact mechanism for this is not known since the average tissue temperature immediately adjacent to the radiofrequency probe does not reach the lower limit for tissue coagulation. Whether it is because of ‘heat spikes’ to temperatures capable of causing tissue damage generated by the pulsatile delivery of radiofrequency current or another mechanism is unknown. What is increasingly clear from the available preclinical evidence, including the important contribution from the article by Choi et al. in this issue, is that pulsed delivery of radiofrequency electrical current to nervous tissue produces a detectable, quantifiable and scientifically interesting lesion in every sense of the word.
150 Eur J Pain 18 (2014) 149–150
R. Carter W. Jones III Department of Anesthesiology, Center for Pain Medicine, University of California San Diego, USA Correspondence R. Carter W. Jones III E-mail: [email protected] Conflicts of interest None declared.
References Bogduk, N. (2006). Pulsed radiofrequency. Pain Med 7, 396–407. Choi, S., Choi, H.J., Cheong, Y., Chung, S.H., Park, H.K., Lim, Y.J. (2014). Inflammatory responses and morphological changes of radiofrequencyinduced rat sciatic nerve fibers. Eur J Pain 18, 192–203. Sluijter, M.E., van Kleef, M. (2007). Pulsed radiofrequency. Pain Med 8, 388–389. Watkins, L.R., Hutchinson, M.R., Milligan, E.D., Maier, S.F. (2007). ‘Listening’ and ‘talking’ to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids. Brain Res Rev 56, 148–169.
© 2014 European Pain Federation - EFIC®
Neuroinflammatory effects of radiofrequency Accepted for publication 9 September 2013 doi:10.1002/j.1532-2149.2013.00418.x
In this issue, you will find a paper by Choi et al. (2014), entitled ‘Inflammatory responses and morphological changes of radiofrequency-induced rat sciatic nerve fibers.’ The paper describes a preclinical study comparing the anatomical and biological effects of radiofrequency treatment on the sciatic nerve of rats using clinically relevant continuous and pulsed mode protocols. Much has been written about the clinical utility of both techniques and there is a great divide among practitioners regarding the value of pulsed mode radiofrequency treatment for appropriate chronic pain conditions. In the United States, many interventional pain physicians may eschew the use of pulsed radiofrequency because of lack of reimbursement from medical insurance companies compounded by mostly poorly designed or under-powered clinical studies (Bogduk, 2006). Proponents of the pulsed mode laud the potential safety benefits of avoiding high-temperature coagulation of nervous tissue as occurs with continuous mode, theoretically limiting adverse side effects and permitting application of radiofrequency electrical current delivery to treat pain emanating from peripheral nerves with important motor functions as well (Sluijter and van Kleef, 2007). The study by Choi et al., in this issue, adds to the mounting preclinical evidence that pulsed radiofrequency produces quantifiable anatomical and functional effects on nerve function. While there are many other studies that have documented alterations in cellular structure and/or function after both types of radiofrequency protocols, this study is important in that it adds further evidence that (1) although both pulsed and continuous radiofrequency treatments produce alterations in neuroanatomy, disruption of cellular structure is much more severe and persistent after continuous than pulsed delivery of radiofrequency electrical current to the nerve; and (2) the degree and duration of anatomical effects produced by the two distinct types of radiofrequency protocols are paralleled by proportionate levels of immune cell activation and proinflammatory cytokine elaboration in the spinal cord. A logical interpretation of these results © 2014 European Pain Federation - EFIC®
is that high-temperature coagulative lesioning of peripheral nervous tissue, as occurs during continuous radiofrequency treatment, leads to a sustained, proinflammatory immune response in the spinal cord that is much diminished in amplitude and duration if pulsed mode is utilized. The extolled safety virtues of pulsed compared with continuous radiofrequency treatment can be measured as both a reduction in motor complications and a reduction in the incidence of deafferentation syndrome (although it has yet to be documented in a head-to-head comparison of both techniques). This study provides further preclinical justification for both propositions, and some of the first evidence that peripheral continuous radiofrequency lesions initiate a robust and sustained glial inflammatory response in the central nervous system. The latter observations are particularly important. Glial activation and cytokine elaboration have recently been implicated as playing pivotal roles in many animal models of chronic pain, most particularly following peripheral nerve injury (Watkins et al., 2007). The activation of this particular proinflammatory and ‘pro-pain’ mechanism by continuous radiofrequency may appear at first glance to be counterintuitive and contrary to the purpose of radiofrequency treatments for chronic pain conditions in general. However, this may be one potential explanation of paradoxical increases in pain seen in patients after radiofrequency treatments. The clinical effect of continuous radiofrequency treatment may therefore reflect a balance between analgesia produced by deafferentation-induced reduction in nociceptive input to the central nervous system and stimulation of proinflammatory, pronociceptive glial activation in the central nervous system as a consequence of deafferentation. Clinical experience indicates that analgesia is more commonly the result; however, central immunemediated inflammation may predominate in patients who experience an increase in pain following the procedure. It is important to note that in this study, no prior intervention was performed to the animals; therefore, the described effects are on naïve animals Eur J Pain 18 (2014) 149–150
149
Commentary
with no iatrogenic nervous system pathology. Whether a similar activation occurs after application of radiofrequency current to injured nerves and if only injury to specific nerves is required for central immune activation is unknown. Given prior preclinical studies of pulsed radiofrequency treatment, documentation of identifiable neural pathology, albeit largely reversible, and limited spinal immune activation as Choi et al. did in this study is not surprising. The exact mechanism for this is not known since the average tissue temperature immediately adjacent to the radiofrequency probe does not reach the lower limit for tissue coagulation. Whether it is because of ‘heat spikes’ to temperatures capable of causing tissue damage generated by the pulsatile delivery of radiofrequency current or another mechanism is unknown. What is increasingly clear from the available preclinical evidence, including the important contribution from the article by Choi et al. in this issue, is that pulsed delivery of radiofrequency electrical current to nervous tissue produces a detectable, quantifiable and scientifically interesting lesion in every sense of the word.
150 Eur J Pain 18 (2014) 149–150
R. Carter W. Jones III Department of Anesthesiology, Center for Pain Medicine, University of California San Diego, USA Correspondence R. Carter W. Jones III E-mail: [email protected] Conflicts of interest None declared.
References Bogduk, N. (2006). Pulsed radiofrequency. Pain Med 7, 396–407. Choi, S., Choi, H.J., Cheong, Y., Chung, S.H., Park, H.K., Lim, Y.J. (2014). Inflammatory responses and morphological changes of radiofrequencyinduced rat sciatic nerve fibers. Eur J Pain 18, 192–203. Sluijter, M.E., van Kleef, M. (2007). Pulsed radiofrequency. Pain Med 8, 388–389. Watkins, L.R., Hutchinson, M.R., Milligan, E.D., Maier, S.F. (2007). ‘Listening’ and ‘talking’ to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids. Brain Res Rev 56, 148–169.
© 2014 European Pain Federation - EFIC®
