Immediate early genes after pulsed radiofrequency treatment: neurobiology in need of clinical trials.

THE search for treatments that relieve chronic pain is expanding and includes biobehavioral techniques, the discovery of new drugs, novel routes of drug administration, neuroablative treatments, and innovative surgical procedures. The use of less invasive, interventional strategies for chronic pain relief has gained popularity since the publication of evidence from randomized controlled trials. Electrical stimulation techniques, such as transcutaneous nerve stimulation and spinal dorsal column stimulation, are attractive treatment options for chronic pain because the intervention can be somatotopically localized and can be removed if effectiveness declines, there are few side effects, and tolerance does not appear to be a problem. Recently, the technique of pulsed radiofrequency treatment, the application of brief, high frequency electrical stimulation adjacent to sensory ganglia, has been described for the relief of chronic, intractable pain. In this issue of ANESTHESIOLOGY, Van Zundert et al. describe changes in the expression of c-fos, an immediate early gene, after pulsed radiofrequency treatment in laboratory rats. Conventional radiofrequency treatment, using a constant output of high-frequency electric current, produces controllable tissue destruction surrounding the tip of the treatment cannula and, when placed at precise anatomic locations, has demonstrated success in reducing a number of different chronic pain states, including chronic neck pain after whiplash injury and trigeminal neuralgia. Pulsed radiofrequency utilizes brief “pulses” of high-voltage, radiofrequency range ( 300 kHz) electrical current that produce the same voltage fluctuations in the region of treatment that occur during conventional radiofrequency treatment but without heating to a degree at which tissue coagulates. The idea arose from a chance meeting during a 1995 scientific conference in Austria between Dr. Menno Sluijter, M.D., Ph.D. (Professor Emeritis, Department of Anesthesia, Maastricht University, Maastricht, Netherlands), a physician who has pioneered the clinical application of radiofrequency treatment, and William Rittman, M.S. (Principal, RF Medical Devices, Middleton, MA), then an engineer with Radionics, the firm that developed the original radiofrequency treatment equipment (personal written communication, William Rittman, October, 2004). The two were discussing the mechanism behind radiofrequency treatment with a basic scientist from the former Soviet bloc who had been examining cellular changes induced by magnetic fields; this scientist challenged the conventional belief that pain relief after radiofrequency treatment was a result of tissue destruction, suggesting that the pain relief could result from the strong magnetic fields induced by voltage fluctuations in the area of treatment. Mr. Rittman returned to the bench and quickly devised a means of creating the same high-voltage fluctuations without any heating at the tip of the needle by using pulses of electrical current rather than continuous current. Dr. Sluijter immediately introduced the technique into clinical practice and within months had treated numerous patients with the new modality; based on this initial, uncontrolled clinical experience, the new technique has been aggressively promoted and its use has rapidly spread worldwide. The conceptual appeal of a minimally invasive, nondestructive technique that is useful in treating chronic pain of any sort is compelling. In clinical practice, there has been a mass migration to the use of pulsed radiofrequency with few data to support efficacy of this new technique. The modality has great appeal, specifically because it is not neurodestructive. With conventional radiofrequency, the thermal lesion occasionally leads to worsening pain and even new onset of neuropathic pain. A small retrospective case series and the overwhelming “word on the street” among practitioners suggest that pulsed radiofrequency results in neither increased pain nor any risk of neuropathic pain, and it is very well tolerated by patients from treatment through recovery. In the study by Van Zundert et al., experimental neurobiologic techniques are used to probe the effects of pulsed radiofrequency on spinal cord sensory neurons. The gene c-fos codes for the production of fos protein and is rapidly and transiently expressed in neurons after an excitatory stimulus. Using immunohistochemical techniques, Hunt et al. first reported that Fos-like-immunoreactivity appears in neurons of the dorsal horn of the spinal cord in rats after noxious stimulation. Subsequently, Fos-like-immunoreactivity has been used as a marker for sensory neuron activation in preclinical animal studies allowing the investigator to determine the number of neurons activated and their segmenThis Editorial View accompanies the following article: Van Zundert J, de Louw AJA, Joosten EAJ, Kessels AGH, Honig W, Dederen PJWC, Veening JG, Vles JSH, van Kleef M: Pulsed and continuos radiofrequency current adjacent to the cervical dorsal root ganglion of the rat induces late cellular activity in the dorsal horn. ANESTHESIOLOGY 2005; 102:125–131.