Why Does Acute Postoperative Pain Become Chronic and Can It Be Prevented?
Can you please explain the phenomenon of postsurgical chronic pain?
Dr. Mackey: We traditionally think of pain after surgery as self-limiting and responding well to short-term medications, and in the vast majority of cases it does. However, a percentage of patients go on to develop persistent pain after surgery that can ultimately become chronic in nature. In fact, we are beginning to realize that the numbers of patients with postsurgical chronic pain are actually higher than we originally appreciated. The burden of chronic postsurgical pain is actually quite large. What do we mean by postsurgical chronic pain? Sometimes it is defined as pain lasting more than 3 or 6 months after surgery, but I, and many others, prefer to define postsurgical chronic pain as pain that persists beyond the expected duration of healing.
What is the incidence of postsurgical chronic pain?
Dr. Mackey: A number of studies suggest a range in incidence of 6% to 40%. The variability is due to a number of factors, not the least of which is the extent of the surgery. I usually quote that, on average, about 10% of patients are at risk for postsurgical chronic pain.
Why does postsurgical chronic pain occur?
Dr. Mackey: It may be worthwhile for people to reconceptualize surgery. The way that I traditionally think of surgery is as nothing more than a controlled injury. When you think of surgery as injury, it becomes amenable to the idea that surgical pain can become chronic. When we think of other injuries such as low back pain, about 90% of patients with this condition will recover but about 10% will go on to have chronic low back pain. We are seeing numbers in a similar range for chronic pain after surgery, and it makes sense because both conditions involve a significant injury. Hence, the problem is probably greater than we anticipated, and, similarly, the impact is probably much greater than we anticipated.
What are the risk factors for postsurgical chronic pain?
Dr. Mackey: We think that surgeries that cause significant nerve injury have the propensity for higher risk for postsurgical chronic pain. For example, thoracotomy that injures the intercostal nerve is much more likely to cause significant pain and significantly more chronic pain than surgery that does not cause an injury to a nerve. Nerve injury is one of the common risk factors that we think of; however, it turns out that there are a large number of factors for postsurgical chronic pain that ultimately have nothing to do with the surgery at all.
Based on NIH-funded work that Ian Carroll, MD, and I are doing here at Stanford, we have identified that what the patient brings to the operating room table often has as much to do with whether the patient has chronic pain after surgery as the surgery itself. This, I think, is eye-opening. We found that factors like preexisting history of post-traumatic stress disorder played a big role in whether people developed persistent pain.
Pain severity on postoperative day 1 also played a big role in delayed pain resolution after surgery in our study. Previous studies have identified that early postoperative pain can play a role in the development of chronic pain, but what we don’t know is whether higher amounts of postoperative day 1 pain are due to the fact that a person underwent a bigger surgery, had more [nerve] stimulation, or is innately more sensitive to pain to begin with.
I am optimistic that we can answer this question, and we are currently researching this topic. I think we can determine pain sensitivities before surgery and then characterize how that impacts pain sensitivity after surgery.
What role do fear and anxiety play in postsurgical chronic pain?
Dr. Mackey: Fear and anxiety are found to play a significant role in individual differences in pain. How much fear and anxiety you have to somatic sensations of pain plays a significant role in what your overall sensitivity to pain is and, at least in some aspects of our models, seems to have an influence in the persistence of pain as well.
In a brain imaging study we performed a few years ago, we identified that the amount of fear and anxiety that people have regarding pain helps shape the individual differences in how much pain they experience from a given stimulus.1 People who have more fear or more anxiety for a given stimulus will have more pain than people who have less fear or anxiety. We were able to characterize brain regions that were responsible for these individual differences. Specifically, the lateral orbitofrontal cortex played a significant role in some of the fear-related individual differences. This brain region is involved with evaluating and regulating responses to potential stimuli.
With somatic anxiety, the medial prefrontal cortex played a significant role. This brain region is involved with more self-focused elaboration of the negative personal implications of pain. Currently, the medial prefrontal cortex is getting a tremendous amount of focus because it also is found to be involved with post-traumatic stress disorder. Basic science researchers have found that the medial prefrontal cortex is a key area involved in descending regulation of the brainstem and some of the inhibitory processes. This brain region may ultimately be a big key regulator in modulating pain (see Figure 1).
Are there ways to prevent postsurgical chronic pain from developing?
Dr. Mackey: There is a body of literature that was published years ago on the beneficial effects of reducing anxiety and fear and improving optimism regarding pain after surgery. What we don’t know is whether reducing anxiety and fear will have any impact on the persistence of pain after surgery. This is a relatively new area of research, and we have to make some inferences that it would. With regard to psychological therapies, there are some tantalizing suggestions, but we don’t have any solid data.
With regard to pharmacologic agents, we are just starting to see data suggesting that some of the classic chronic pain medications given during the time of surgery may reduce the risk for developing chronic pain. We have seen suggestions that a drug like pregabalin (Lyrica), which works on neuropathic pain, may reduce the incidence of postsurgical pain. For example, a recent study found that pregabalin reduced the incidence of chronic pain after total knee replacement.2 Because we know that anxiety plays such an important role in chronic pain, one question that we have is whether pre-gabalin is really reducing nociception or whether it is reducing the persistence of pain through its actions as an anxiolytic. This is nothing more than our hypothesis at this time, but one that we are testing in a controlled trial.
In addition, evidence suggests that ketamine, an N-methyl-d-aspartate (NMDA) antagonist, given during the perioperative period can reduce the incidence of chronic postoperative pain. Other agents also are being tested.