Testing the Link between Sympathetic Efferent and Sensory Afferent Fibers in Neuropathic Pain

The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic -adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done inrandom order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25–35 mg). The pain relief achieved by LASB and PhB correlated closely (r 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t 0.19, P 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that -adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP. A T the 2000 spring meeting of the editorial board of ANESTHESIOLOGY, Dr. Michael Todd, then editor-inchief of ANESTHESIOLOGY, and the board members were brainstorming ideas to enhance the journal’s educational value to the readers in the new millennium. I suggested a new * Professor of Anesthesiology and Professor of Neurology, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland. † Professor, Chair of Neurophysiology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Received from the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, and the Department of Neurophysiology, University of Heidelberg, Mannheim, Germany. Submitted for publication March 6, 2012. Accepted for publication March 29, 2012. Supported by grant no. NS-26363 from the National Institutes of Health, Bethesda, Maryland (to Dr. Raja). Figure 2 was prepared by Annemarie B. Johnson, C.M.I., Medical Illustrator, Wake Forest University School of Medicine Creative Communications, Wake Forest University Medical Center, Winston-Salem, North Carolina. Address correspondence to Dr. Raja: Division of Pain Medicine, Department of Anesthesiology/CCM, Johns Hopkins University, 292 Osler, 600 N. Wolfe Street, Baltimore, Maryland 21287. sraja2@jhmi.edu. This article may be accessed for personal use at no charge through the Journal Web site, www.anesthesiology.org. Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2012; 117:173–7 Anesthesiology, V 117 • No 1 July 2012 173 Downloaded from anesthesiology.pubs.asahq.org by guest on 05/04/2019 section that could highlight publications related to anesthesiology, critical care medicine, and pain that are regarded as classics because of their scientific or clinical impact. During the subsequent 6 yr as editor of this Classic Papers Revisited section, I had the pleasure of corresponding with several giants in our field who graciously contributed insightful articles to the section, despite many being in the midst of their retirement. Recently, I was pleasantly surprised to receive an invitation from Dr. David Warner to contribute an article to this section on our paper published two decades ago in this journal. It was, however, not without a bit of trepidation that I accepted the invitation, for during the early years, more than 50% of the authors who were invited to contribute an article for this section passed away within a year of having their manuscript published. From Bench to Bedside Research After my residency in anesthesiology at the University of Washington, Seattle, under the chairmanships of Drs. John Bonica and Thomas Hornbein, I was fortunate to be offered a postdoctoral research position by Dr. Robert Epstein at the University of Virginia, Charlottesville, in 1979. My introduction to research and neurophysiology in the laboratory of Dr. Patrice Guyenet (professor of pharmacology) was studying the mechanisms of action of phencyclidine (angel dust) and its derivative, ketamine, on the central nervous system. In 1981, I joined the faculty at Johns Hopkins and was introduced to pain research by my mentors Richard Meyer and James Campbell in the Department of Neurosurgery (fig. 1). During the first several years of our research, we focused on understanding the peripheral signaling of pain from the skin under normal conditions and after acute injury by using neurophysiologic studies in primates and parallel psychophysical studies in humans. Subsequently, we examined the altered pain signaling that occurred after injury to