Friday, June 14, 2013

Anesthesiology News - Progress, If No Breakthroughs, in Chronic Post-op Pain

The emerging recognition that many patients develop chronic pain after surgery has spurred a host of behavioral and anatomic research.

So far, these studies have yet to produce any breakthroughs in the understanding, and more importantly for patients, the treatment of the problem. But during a session at the 2012 annual meeting of the American Society of Anesthesiologists, experts said the question was not whether, but when, those treatments would arrive.

"Not surprisingly, chronic postsurgical pain has become a popular topic," said Timothy Brennan, MD, PhD, the Samir Gergis Professor and Vice Chair for Research at the University of Iowa's Roy J. and Lucile A. Carver School of Medicine, in Iowa City. "Compared with a patient who develops an injury after a car accident, with surgical patients we know when our patients are going to get injured, and we know what type of injury is going to occur: the surgery. So, I think our goal will be to study surgical patients and evaluate their pain responses when they don't have this premeditated injury, then follow them through the postoperative period in the hope that we can learn to predict chronic postsurgical pain and the factors related to its development."

Several studies have associated the development of chronic postsurgical pain and other unfavorable long-term outcomes with somatic and psychological predictors. A 2007 Dutch investigation (Ann Surg 2007;245:487-494) in 625 patients, for example, found that psychological factors such as fear of long-term consequences and lack of optimism were predictors of persistent pain, disability and low quality of life after surgery.

"I think, sometimes, functional limitations and lower quality of life may impact a patient's perception of their pain and certainly the development of persistent pain afterward," Dr. Brennan noted. "This reminds us that there are many psychological factors associated with the development of persistent pain."

More recently, a team of Norwegian researchers followed more than 12,000 patients, 2,043 of whom had undergone surgery within three months of the start of the study (Pain2012;153:1390-1396). Persistent pain in the area of surgery was reported by 40.4% of the patients. The researchers also found strong associations between sensory abnormalities and persistent pain. "Broad studies such as these cast a wide net, and are certainly continuing to point to this relevant problem of disability after surgery and significant pain reports," Dr. Brennan said.

Few studies, however, have shed as much light on the anatomic changes that occur in response to pain as a longitudinal investigation by Baliki and colleagues, reported last year inNature Neuroscience (2012;15:1117-1119), to determine the mechanism of brain reorganization as pain moves from acute to chronic.

The researchers followed patients with subacute back pain for more than a year, stratifying them into those whose pain did not resolve and those whose pain improved, and also compared them with a group of healthy controls. Patients whose pain persisted showed decreases in the density of gray matter in the brain.

"The researchers also looked at the connectivity between various parts of the pain network and what I call the emotional network," Dr. Brennan said. They found that an initially greater level of connectivity between a section of the brain called the nucleus accumbens, which is critical to the sensation of pleasure, and the prefrontal cortex predicted pain persistence. This increased connectivity, they inferred, suggests that corticostriatal circuitry is causally involved in the transition from acute to chronic pain.

"The medial prefrontal cortex is one of those areas in the brain that signals the affective component of pain," Dr. Brennan explained. "When pain is well connected to the nucleus accumbens, pain pathways are strongly linked to psychological pathways. This link was found to be an accurate predictor of the transition from subacute to chronic pain. Now, whether or not this applies to a perioperative situation certainly remains to be seen," he continued. "We know that there are similarities between back pain patients and postsurgical patients, but more research needs to be performed."

For clinicians, of course, the physiology of how postoperative pain becomes chronic is most important if it leads to ways of preventing the transformation. "The literature suggests it may not be that easy," Dr. Brennan said.

Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University, in Philadelphia, noted that the magnitude of chronic postsurgical pain is vastly underestimated by most anesthesiologists and surgeons.

"I agree with Dr. Brennan that a link with severe acute pain alone is probably too simplistic," said Dr. Viscusi, a member of the editorial board of Anesthesiology News. "My opinion is that since the causes are likely multifactorial, there will not be a single solution. What's more, some patients may just have an inherent risk. Nevertheless, several interesting studies support that preoperative and postoperative pregabalin [Lyrica, Pfizer] and ketamine may reduce longer-term pain after surgery. The best current evidence suggests that a multimodal analgesic approach and adjustment of surgical technique may make a difference."