14th Annual Journal Symposium: Plasticity in Postoperative Pain
Tuesday, October 25, 2005, 9:00 am to 12:30 pm, in La Nouvelle Orleans A, New Orleans Morial Convention Center, New Orleans, Louisiana
The 14th Annual Anesthesiology Journal Symposium examines the evidence and role for neuroplasticity in postoperative pain. Neuroplasticity is the process whereby tissue injury increases the responsiveness of the sensory system so that later stimuli produce a much greater effect. The Symposium will examine the plasticity processes caused by surgery and how anesthesia and acute postoperative pain management might influence these phenomena.
Pain research has emphasized the molecular transduction of painful stimuli, the sensitization processes that occur after injury and long-term phenomena such as pain memory. Neuroplasticity after surgery may occur at the transduction process, in the periphery at the subcellular level, or in the central nervous system, where central sensitization occurs.
Perioperative medicine has repeatedly sought to identify early, short-term treatments resulting in long-term benefits in the acute postoperative period. For acute postoperative pain management, this began 15 yr ago with the publicity surrounding preemptive analgesia and early treatment before surgery reducing postoperative pain more than the same treatment administered later. This excitement has continued into other areas such as identifying treatments that prevent acute postoperative pain, have greater-than-expected durations of clinical benefit, or interfere with sensitization processes causing postincisional pain. The perioperative use of ketamine and gabapentin are examples of such treatments. Compared with many other acute and chronic pain problems, the best opportunity to influence the development of a pain may indeed be during surgery, because preoperative factors can be assessed. The timing and extent of the injury, the magnitude of the acute pain, and the impact on function are understood.
Neuroplasticity in postoperative pain has far greater impact than the acute perioperative period. Pain and disability can persist weeks after surgery, but little is known about this problem, sometimes called residual pain , and its prevention and treatment. In the past 5 yr, there has been increasing interest in persistent or chronic pain after surgery. Preoperative, intraoperative, and postoperative factors involved in the development and maintenance of persistent pain problems such as postthoracotomy syndrome, phantom limb pain, or post-herniorrhaphy syndrome are beginning to be examined.
Perioperative medicine will benefit as we understand mechanisms for incision-induced peripheral and central sensitization, the components of neuroplasticity. Quantifying neuroplasticity in patients after surgery will add to our understanding of acute postoperative pain processing. Finally, the role of preoperative testing for predicting acute postoperative pain, residual pain after surgery, and chronic pain has begun.
The goal of this field will be painless or nearly painless surgery with few side effects, identifying patients whose acute pain is difficult to manage, and predicting and preventing chronic pain after surgery.
The Symposium will be moderated by Timothy J. Brennan, Ph.D., M.D., and Srinivasa N. Raja, M.D., of The University of Iowa, Iowa City, Iowa, and Johns Hopkins University, Baltimore, Maryland, respectively. The speakers include
Timothy J. Brennan Ph.D., M.D., Assistant Editor-in-Chief, Anesthesiology, Associate Professor, Departments of Anesthesia and Pharmacology, The University of Iowa, Iowa City, Iowa
Gary R. Strichartz, Ph.D., Professor of Anesthesia, Pharmacology and Biophysics, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts
Troels S. Jensen, M.D., Ph.D., Professor, Department of Neurology, Aarhus University, and Danish Pain Research Center, Aarhus, Denmark
Henrik Kehlet, M.D., Ph.D., Professor of Surgery, Section for Surgical Pathophysiology, The Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark
Speakers will provide an overview and focused information on how the nervous system is sensitized to produce postincisional pain and the clinical manifestations and relevance of these processes. These lectures will be accompanied by the presentation of 11 posters selected for their relevance to the Symposium topic.
Dr. Brennan will review sensitization of primary afferent nociceptors, peripheral sensitization, and sensitization of dorsal horn neurons, one manifestation of central sensitization, by incisions. Mechanisms for activation of primary afferent neurons and dorsal horn neurons by incisions will be examined. Neuroplasticity of incisional pain and its implications for perioperative pain management will be discussed.
Dr. Strichartz will discuss postincisional pain in the hairy skin of the rat, which is characterized by tactile allodynia and hyperalgesia, next to the incision site (primary responses ) and at a distance, including on the contralateral side (secondary responses ). Delivery of subcutaneous bupivacaine at the incision site before surgery reduces the acute increase of primary allodynia and almost abolishes secondary responses; the same dose delivered away from the incision also strongly abolishes secondary allodynia. It seems that both locally acting and systemic bupivacaine inhibit the hyperesthetic reactions to skin incision, and for times that far exceed their duration of nerve block.
Dr. Jensen will examine the clinical manifestations of neuronal hyperexcitability, including spontaneous pain in the damaged territory, decreased pain threshold, pain induced by nonnoxious stimuli, extraterritorial spread of pain, and sensory abnormalities within and outside the territory. Surgical procedures represent excellent clinical models for studying neural plastic changes, and the manifestations can be chased to the site of injury, the spinal cord, and to various relays in the brain. In the majority of cases, neural plastic changes are transient, but in a few cases, pain and associated plastic changes persist. The neuronal plastic changes after nerve injury, amputation, mastectomy, and other procedures will be illustrated.
Dr. Kehlet will review the incidence of persistent postoperative pain. This will be followed by a focus on pathogenic mechanisms with special attention to the role of surgical techniques preventing intraoperative nerve damage. Dr. Kehlet will also discuss predisposing factors, including hereditary aspects and the potential role of improved postoperative pain relief to reduce persistent postoperative pain.
In addition to the lectures noted above, 11 posters will be presented and available for discussion at the Symposium. Areas of interest include treatments to prevent pain after surgery, a central action of prostaglandins in acute pain, and evaluation of persistent pain after surgery. The lectures will provide a basis for the discussion of the selected abstracts. The text for each abstract can be found on the ASA Abstract Web site or in the CD-ROM that is included with this issue of the Journal.
“Preemptive Analgesia in Laparoscopic Cholecystectomy Patients Simplifies Their Postoperative Pain Control” by Olexandr P. Maslovsky, Mykola D. Besaraba. Khmelnitsky Central Hospital, Khmelnitsky, Ukraine [A1475]
“Effect of Cyclooxygenase Inhibitors on Cerebrospinal Fluid (CSF) Prostaglandin E2(PGE2) after Surgery” by Scott S. Reuben, Asokumar Buvanendran, Jeffery S. Kroin, Michael English. Baystate Medical Center, Springfield, Massachusetts [A1476]
“Upregulation of Interleukin-6 (IL-6), but Not IL-1β or TNF-α, in the Central Nervous System in the Perioperative Period” by Asokumar Buvanendran, Jeffrey S. Kroin, Chiranjeev Saha, Nadim J. Hallab, Richard A. Berger. Rush Medical College, Chicago, Illinois [A1477]
“Perioperative Perineural Infiltration of Bupivacaine and Clonidine at the Site of Injury following Lower Extremity Amputation” by Scott S. Reuben, Scott Roissing, Holly Maciolek, Steven Silver. Baystate Medical Center, Springfield, Massachusetts [A1478]
“Pain and Hyperalgesia One Day after Plantar Incision in Rats Are Related to Dorsal Horn Neuron Sensitization” by Philippe Richebe, Timothy Brennan. The University of Iowa, Iowa City, Iowa [A1479]
“Age-dependent Up-regulation of Cyclooxygenase-1 in the Spinal Cord after Surgery in Rat” by D. G. Ririe, H. M. Prout, D. K. Barclay, C. Tong, J. C. Eisenach. Wake Forest University School of Medicine, Winston-Salem, North Carolina [A1480]
“Predictive Criteria of Postoperative Pain (POP) of Shoulder Surgery: Which Place for Regional Anesthesia (RA)?” by Michel Carles, Mike Blay, Guy Armando, Pascal Boileau, Marc Raucoules-Aime. University Hospital, Nice, Alpes Maritimes, France [A1481]
“The Effect of Perioperative Ketamine Infusion on the Development of Persistent Pain after Thoracotomy” by Manzo Suzuki, Yoichi Shimada. Second Hospital Nippon Medical School, Kawasaki, Kanagawa, Japan [A1482]
“Effects of Systemic Administration of Lidocaine and QX-314 on Hyperexcitability of Spinal Dorsal Horn Neurons after Incision in the Rat” by Mikito Kawamata, Toshiyuki Takahashi, Eichi Narimatsu, Tomohisa Niiya, Akiyoshi Namiki. Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan [A1483]
“Predictors of Postoperative Pain and Analgesic Requirement after Cesarean Delivery” by Peter H. Pan, James C. Eisenach, Robert Cogill, Lynne Harris. Wake Forest University School of Medicine, Winston-Salem, North Carolina [A1484]
“Effect of Systemic and Intrathecal COX Inhibitors on CSF Prostaglandin E2 Levels following Thoracic Surgery in the Rat” by Jeffrey S. Kroin, Asokumar Buvanendran, Daniel E. Watts, Chiranjeev Saha, Kenneth J. Tuman. Rush Medical College, Chicago, Illinois [A1485]
SOAP/Journal Abstract Session: Basic Mechanisms Underlying Our Routine Daily Practices of Obstetric Anesthesia
Monday, October 24, 2005, 2:00 to 3:30 pm, in Room 392, New Orleans Morial Convention Center, New Orleans, Louisiana
The 2005 Annual Meeting of the American Society of Anesthesiologists in New Orleans, Louisiana, will feature the second special research session jointly sponsored by the Society for Obstetric Anesthesia and Perinatology (SOAP) and Anesthesiology. This special session, first held at the American Society of Anesthesiologists Annual Meeting in 2003, is an example of the strength of the collaboration between the Journal and SOAP. In 1999, Anesthesiology became the official journal of SOAP. This affiliation has strengthened both entities. Anesthesiology is the official home for the best and most innovative obstetric anesthesia research and clinical publications, and SOAP benefits from the wide dissemination of its message that a journal such as Anesthesiology can offer. The session in 2003 was well attended and lively. The six abstracts selected for oral presentation in the upcoming 2005 session are briefly discussed below.
The field of pharmacogenetics once again has brought us some of the most interesting research findings in recent years. We have all heard patients say things such as, “I always need three injections of novocaine at the dentist,”“Tylenol® just doesn’t seem to work for me,” or “Give me a small dose; I am very sensitive to all medications.” Although many of us scoff at comments such as these and attribute them to either patient idiosyncrasy or normal population variability (which may still be valid explanations), many of these patients’ observations may be rooted in genotype. Two abstracts, emanating from the collaborative work of Drs. Ruth Landau and Richard Smiley from the University of Geneva, Switzerland, and Columbia University, New York, New York, respectively, explore these phenomena in greater depth. “Genotype of the μ-Opioid Receptor (A118G) Influences the E50of Intrathecal Fentanyl for Early Labor Analgesia”[A1469] describes a polymorphism of the μ-opioid receptor that can be associated with significant differences in the clinical analgesic response to a dose of intrathecal fentanyl during labor. “Effect of β-2-Adrenergic Genotype on Response to Treatment of Hypotension during Spinal Anesthesia for Cesarean Section”[A1472] demonstrates that a polymorphism of the β2-adrenergic receptor can significantly influence the incidence of hypotension after spinal anesthesia for cesarean delivery. Someday, we might all know our own entire genotypical make-up, just as we now know our myriad of personal identification (PIN) numbers. The implications for clinical care, although speculative at present, are huge.
The controversy surrounding maternal temperature increase during labor with epidural analgesia has been a great concern to anesthesiologists and others during the past decade. It is now a well-established fact that epidural analgesia is associated with, and likely causal in, the increase in temperature often seen during labor. The mechanism and clinical implications for this finding are less clear. “Immunohistochemical Localization of Activin Subunit in Human Placenta: Correlation with Elevated Temperature and Placental Infection in Parturients Laboring under Epidural Analgesia”[A1470] (Peter Szmuk, Rumelia Koren, Tiberiu Ezri, Dov Zipori, Shmuel Evron; University of Texas Medical School, Houston, Texas) attempts to determine whether the finding is related to an infectious etiology or some other mechanism. Examination of placental markers of infection and inflammation may help us to obtain a better understanding of this clinical puzzle.
Two abstracts examine our ability to predict various adverse effects of concern during and after cesarean delivery. “Heart Rate Variability Guided Prophylaxis of Hypotension after Spinal Anesthesia for Elective Cesarean Section”[A1471] (Robert Hanss, Berthold Bein, Wiebke Scherkl, Jens Scholz, Peter H. Tonner; University Hospital Schleswig-Holstein, Kiel, Germany) uses the innovative approach of examining maternal heart rate variability before surgery. This analysis can predict the incidence of hypotension after spinal anesthesia. Consequently, a tool could be developed that can be used to guide which patients may benefit from prophylactic administration of vasopressors. “Predictors of Postoperative Pain and Analgesic Requirement after Cesarean Delivery”[A1474] (Peter H. Pan, James C. Eisenach, Robert Coghill, Lynne Harris; Wake Forest University, Winston-Salem, North Carolina) examines a variety of simple preoperative tests that can help to predict the incidence and severity of post–cesarean delivery pain. The entire phenomenon of post–cesarean delivery pain, particularly long-term pain and its consequences, is one that is only now beginning to be recognized as an important clinical entity, resulting in frequent patient morbidity and dissatisfaction in the months or years after delivery. If we can accurately predict which patients are more likely to experience these adverse effects, we can, in theory, offer more aggressive postoperative pain control targeted at easing both short- and long-term recovery.
“Expression of CGRP and SST in Neurons Innervating the Uterine Cervix”[A1473] (Brittany B. Clyne, Dawn R. Conklin, James C. Eisenach, Chuanyao Tong; Wake Forest University, Winston-Salem, North Carolina) examines the important concept of the molecular mediators of pain in the uterine cervix. The clinical implication of this work relates to the enhanced understanding of how pain is transmitted from the reproductive organs and, in particular, how this may differ, if at all, in the pregnant versus the nonpregnant state. Moreover, the possibility may exist, based on work such as this, for the development of nonopioid, nonlocal anesthetic drugs for analgesia during labor and delivery.
This special session promises to be educational and lively. Please join us to celebrate the presentation and discussion of these fine scientific works.