Abstract
Most people will require surgery during their lifetime, and, for a significant proportion, this will lead to chronic postsurgical pain. The incidence of chronic pain after surgery varies significantly by site of surgical procedure; however most reports support an incidence of at least 10% of patients having pain 1 year after surgery. This patient population suffers a significant cost in terms of the related distress, lost productivity, and emotional anguish. There are many factors that can contribute to the likelihood of developing acute and chronic postsurgical pain. Achieving a better understanding of these factors has helped in developing more appropriate treatments and preventative interventions that can help with the prevention and treatment of chronic postsurgical pain. Good perioperative analgesia and minimization of tissue injury continue to be important goals for both anesthesiologists and surgeons in the perioperative period. Multimodal analgesia remains the simplest method by which anesthesiologists could have an impact on the development on chronic postsurgical pain (CPSP) along with the addition of screening for psychological risk factors and the identification of high-risk surgeries. Identifying high-risk patients with psychological, genetic, and other preoperative risk factors should help with targeting these patients to ensure that they are managed appropriately. This chapter will discuss the extent of the problem of CPSP, the factors associated with development, the typical presentation of CPSP, the genetics of CPSP, and possible methods of preventing CPSP.
Keywords
chronic pain, chronic pain prevention, neuropathic pain, persistent postoperative pain, postoperative chronic pain, postsurgery pain
Approximately 40 million surgical procedures take place across North America each year, and by most conservative estimates, 10%–15% of those patients will go on to suffer chronic pain 1 year after surgery. In fact, a recent US national survey of the incidence, patient satisfaction, and perceptions of postsurgical pain by Gan et al. showed that 74% of patients experienced postdischarge moderate to severe pain after surgery. Gan et al. also demonstrated that 80% of the surveyed population were worried about postoperative pain compared with 58% 10 years ago, demonstrating that postoperative pain is a growing concern. This is a silent epidemic of devastating proportions both for those who suffer the pain and the associated emotional costs related to distress and for society as a whole, who bear the financial cost of lost productivity and treatment of pain-related problems. Investigations in recent years have given better definitions of the extent of the problem, some of the factors that may predict the onset of chronic pain after surgery, and methods of preventing chronic pain. In addition, the future will bring us better definitions of the genetic basis of development of chronic pain, allowing us to better counsel patients prior to different types of surgery regarding the risk of chronic pain in relation to surgery and possibly allowing us to better aim the most intensive treatments at those patients to reduce morbidity. This chapter will discuss the extent of the problem of chronic postsurgical pain (CPSP), the factors associated with development, the typical presentation of CPSP, the genetics of CPSP, and possible methods of preventing CPSP.
What is Chronic Pain After Surgery?
Without a good definition, it is not possible to estimate the extent of a problem. Very few papers examining the epidemiology of chronic pain after surgery have used a consistent definition. This absence has led to large variability in the estimation of chronic pain across different studies, and has slowed progress in acquisition of knowledge in this area.
Macrae and Crombie, in their original paper on chronic pain after surgery, proposed a working definition as follows:
- 1.
The pain should have developed after a surgical procedure.
- 2.
The pain should be of at least 2 months’ duration.
- 3.
Other causes of the pain should be excluded (e.g., recurrence of malignancy or infection).
- 4.
The possibility that the pain is continuing from a preexisting problem should be explored and exclusion attempted.
This was the first worthy attempt to define CPSP, and future studies would benefit from using such a consistent definition. In a recent British Journal of Anaesthesia (BJA) editorial, Werner et al. presented revised criteria ( Table 18.1 ) based on more recent data that are more in line with the International Association for the Study of Pain (IASP) definition, which states that the pain has to persist “past the normal time of healing.” However, an obvious problem with this definition is that some types of CPSP are related to a preexisting preoperative painful condition (e.g., phantom limb pain). Nevertheless, the use of a consistent definition of CPSP in the future will significantly help develop an accurate description of the extent of the problem and allow better focus on the areas of greatest need.
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Epidemiology of Chronic Pain After Surgery
The incidence of chronic pain after surgery varies significantly by site of surgical procedure ( Table 18.2 ); however, most reports support an incidence of at least 10% of patients having pain 1 year after surgery. Several high quality reviews in the last 10 years have highlighted the problem of chronic pain after surgery. Crombie, Davies, and Macrae highlighted the problem with their survey of greater than 5000 patients presenting to North British pain clinics and found that surgery contributed to pain in 22.5% of those patients. In particular abdominal, anal, perineal, and genital pain were associated with surgical procedures. Perkins and Kehlet reviewed the evidence for chronic pain after surgery and found an incidence of phantom limb pain of 30%–81%, greater than 50% for chronic postthoracotomy pain, postmastectomy pain syndrome in 11%–57%, phantom breast pain in 13%–24%, and postbreast-surgery arm and shoulder pain in 12%–51%. Chronic pain after cholecystectomy is common (3%–56%), and the overall incidence of chronic pain after inguinal hernia surgery is 11.5%. Joris et al. has also recently shown in a retrospective analysis that the incidence of CPSP after colorectal surgery can be up to 17%.
| Study | Surgical Procedure | Patients With Data | Follow-Up | Incidence of Chronic Pain |
|---|---|---|---|---|
| Nikolajsen et al. | Amputation | 60 | 1 year | Phantom pain 70% |
| Richardson et al. | Amputation | 52 | 6 months | Phantom pain 78.8% |
| Jensen et al. | Amputation | 58 | 2 years | Phantom pain 59% |
| Tasmuth et al. | Breast surgery | 93 | 1 year | 13%–33% |
| Nikolajsen et al. | Cesarean section | 220 | 1 year | Scar pain 12.3% |
| Aasvang et al. | Hernia repair | 694 | 1 year | 56.6% |
| Nikolajsen et al. | Hip replacement | 1048 | 12–18-month prevalence | 12.1% moderate to very severe pain |
| Borly et al. | Open cholecystectomy | 80 | 1 year | 26% |
| Meyerson et al. | Sternotomy for cardiac surgery | 318 | 1 year | 28% |
| Katz et al. | Thoracotomy | 23 | 18 months | 52% |
| Perttunen et al. | Thoracotomy | 67 | 1 year | 61% |
| Gotoda et al. | Thoracotomy | 91 | 1 year | 41% |
In the last 15 years, despite improvements in methods of providing acute pain control, there have been no dramatic improvements in the incidence of chronic pain after surgery. Studies examining pain after inguinal hernia repair, breast surgery, thoracic surgery, and hip surgery indicate that a very conservative estimate of approximately 10% of patients continue to suffer chronic pain following many types of surgery. As outlined previously, this number grossly underrepresents the true incidence, as also evidenced in the more current literature, which indicates an incidence closer to 40%.
Factors Associated with Chronic Pain After Surgery
Factors that are associated with an increased likelihood of developing chronic pain after surgery are summarized in Table 18.3 . It is not known at the present time whether all of these factors are causally related (as opposed to associations) to the development of chronic pain. These factors can be divided into preoperative, intraoperative, and postoperative factors. Preoperative factors include moderate to severe preoperative chronic pain, repeat surgery, and psychological factors. Intraoperative factors include surgery in a low volume center, surgical approach (open vs. laparoscopic), and intraoperative nerve injury. Postoperative factors include acute pain (moderate to severe), radiation therapy, and neurotoxic chemotherapy. In a recent multicenter prospective observational trial, multivariate analysis identified orthopedic surgery, preoperative pain, and percentage of time in severe pain as risk factors. In fact, in this study, the authors stated that “a 10% increase in the percentage of time in severe pain was associated with a 30% increase in the incidence of CPSP.”
| Preoperative Factors | Intraoperative Factors | Postoperative Factors |
|---|---|---|
| Pain—moderate to severe of greater than 1- month duration | Surgical approach with risk of nerve injury | Acute pain—moderate to severe |
| Repeat surgery | Nonlaparoscopic technique | Neurotoxic chemotherapy |
| Psychologic factors | Surgery in low volume center | Radiation therapy to site |
Preoperative Factors
Preoperative pain: A consistent factor associated with the development of acute and chronic postsurgical pain across many types of surgery is the presence of preoperative pain. This is of particular relevance to anesthesiologists, because we are often the main advocates for good quality postoperative pain management. The presence of preoperative pain is a risk factor for the development of early acute postoperative pain—pain in the days, weeks, and months following surgery. A further amplifying factor is that the presence of severe acute postoperative pain also is a risk factor for development of chronic postsurgical pain. Kalkman et al. examined preoperative factors predicting severe acute pain after surgery and found independent predictors of severe pain, including preoperative pain, female gender, younger age, incision size, and type of surgery. Thomas et al. examined patients having hip or knee replacement and spinal decompressive surgery, and also found that predictors of severe postoperative pain included preoperative pain, female gender, and younger age. A very consistent factor in the development of CPSP is the presence of either severe preoperative pain, postoperative pain, or both. No other patient factor is as consistently related to the development of CPSP as pain itself.
Several factors may explain the consistent relationship of preoperative and severe acute postoperative pain predicting chronic postsurgical pain, including:
- 1.
Preoperative opioid tolerance leading to underestimation and underdosing of postoperative opioid analgesics
- 2.
Intraoperative nerve damage and the associated central nervous system changes, such a central sensitization and “wind-up”
- 3.
Sensitization of pain nociceptors in the surgical field
- 4.
Postoperative ectopic activity in injured primary afferents and collateral sprouting from intact nociceptive Aδ afferents neighboring the area supplied by injured afferents
- 5.
Central sensitization induced by the surgery and maintained by further input from the surgical site during the healing process
- 6.
Structural changes in the central nervous system (plasticity) induced by nociceptive inputs with consequent reduction in normal inhibitory control systems leading to “centralization” of pain and development of pain memories
- 7.
Heretofore unidentified pain genes that may confer increased risk of developing both severe acute and chronic postsurgical pain
- 8.
Psychological and emotional factors such as emotional numbing and catastrophizing (discussed later)
- 9.
Social and environmental factors such as solicitous responding from significant others and social support (discussed later)
- 10.
Response bias over time—that is, some individuals have a tendency to report more pain than other individuals
- 11.
Publication bias in which findings of a significant relationship between pain before and after surgery are published, whereas negative findings are rejected and do not get published
Psychosocial Factors and CPSP
Several psychosocial predictors of chronic postsurgical pain have been identified including increased preoperative anxiety, an introverted personality, less catastrophizing, social support and solicitous responding in the week after amputation, higher emotional numbing scores at 6 and 9 months, fear of surgery, and “psychic vulnerability.” To further support this point, Pinto et al. demonstrated in her prospective study looking at postsurgical pain in women undergoing hysterectomy that presurgical and postsurgical anxiety, pain catastrophizing, and emotional illness revealed a predictive role in CPSP.
Pain catastrophizing relates to unrealistic beliefs that the current situation will lead to the worst possible pain outcome. Lewis et al. demonstrated in their systematic review and meta-analysis that even though preoperative pain was the major contributing factor to patients developing CPSP, catastrophizing and the presence of mental health disorders were also strong predictors of persistent pain after total knee arthroplasty. Consistently in the pain literature, chronic pain patients who do not catastrophize fare better than patients who do. It is therefore somewhat paradoxical that the opposite has been found in the prediction of patients who are at risk of CPSP, and may be an artefact of the method by which data were collected.
Solicitous responding refers to the behaviors on the part of spouses or significant others who unwittingly reinforce patients’ negative behaviors and thereby increase their frequency of occurrence. For example, an empathic spouse may reinforce negative behavior by insisting that her partner rest when in fact a more appropriate response would be to encourage activity. Such solicitous behaviors may in fact have the unintended consequence of increasing pain-related behaviors and contributing to pain-related disability. The reader is directed to the comprehensive review by Katz and Seltzer for further information.
Intraoperative Factors
Three main surgical factors have a possible influence on the incidence of CPSP:
- 1.
Experience of the surgeon.
The experience of the surgeon can affect morbidity following surgery. Tasmuth et al. studied patients after breast cancer surgery and found that patients who had surgery in low volume units suffered more CPSP than patients in specialist units where higher numbers of patients had surgery. Other studies, however, have shown equivocal results. Courtney et al. demonstrated no correlation between the grade of surgeon and severe pain after hernia repair.
- 2.
Avoidance of intraoperative nerve injury.
Many basic science studies have successfully demonstrated that intentional nerve injury in animals produces behaviors that resemble symptoms of neuropathic pain in humans. It would therefore make sense during surgical procedures on humans to reduce, as much as possible, any chance of causing intraoperative nerve injury. Many CPSP syndromes occur following surgery around significant nerve structures. Examples include pain after inguinal hernia repair (ilioinguinal and iliohypogastric nerves), axillary dissection (intercostobrachial nerve), and postthoracotomy pain (intercostal nerves). When a nerve is injured, it emits a long-lasting, high frequency burst of activity. This activity is transmitted to the central nervous system, where the massive excitatory stimulus activates postsynaptic N-methyl- d -aspartate (NMDA) receptors, leading to excitotoxic destruction of inhibitory interneurons, disinhibition of pain pathways, and increased postoperative pain. The avoidance of intraoperative nerve injury would be a useful preventative measure and should be attempted wherever possible.
- 3.
Use of minimally invasive surgical techniques where possible.
Although the size of the surgical procedure does not correlate well with incidence of CPSP, the type of procedure and how it is performed can influence CPSP. Wallace and colleagues studied the incidence of chronic pain after different types of breast surgery and found that mastectomy had a much greater incidence of CPSP (53%) compared with breast reduction surgery (22%). Inguinal hernia repair appears to show significant reductions in CPSP when a laparoscopic technique is used, as compared with an open approach, and these results have been confirmed by several studies. The use of lightweight mesh during open incisional hernia repair seems to be associated with less CPSP, without increasing the risk of postoperative complication. Unfortunately, Garcia-Torado et al., in their review of the literature of studies focusing on the most adequate surgical procedure for prevention of CPSP in thoracotomy patients, demonstrated that there is very little scientific evidence in the prevention of postthoracotomy pain. Further studies looking at surgical techniques and the prevention of CPSP will be helpful in guiding patient therapy.
Genetic Factors
The study of the genetics of pain is in infancy, and there are no current research reports that provide data on genes that may predispose patients to chronic postsurgical pain. There are only a handful of reports that identify polymorphisms in human genes associated with chronic pain, including COMT (encoding catechol-O-methyl transferase), 5-HTTLPR (the gene encoding the serotinin transporter that has been found to associate significantly with severity of migraine), burning mouth syndrome, irritable bowel syndrome, and fibromyalgia. IL1RN (encoding the IL-1 receptor antagonist) and MC1R (encoding the melanocortin-1 receptor) in vulvodynia, IL23R in Crohn disease, and GCH1 (encoding GTP cyclohydrolase, an enzyme catalyzing tetrahydrobiopterin, BH4, an essential cofactor for catecholamine, serotonin, and nitric oxide production) have been implicated in persistent radicular pain following discectomy. Recent work has examined OPRM1 (encoding the mu opioid receptor) including a systematic review that attempted to determine the relationship of this gene to opioid sensitivity, side effects, or pain levels. Only 7% of the overall variance could be explained by genetic factors, and the authors concluded that only a minor degree of variance in the clinical setting could be related to pharmacogenetic factors. Montes et al. demonstrated in their multicenter cohort study looking at patients having inguinal hernia repair, hysterectomy, and thoracotomies that an uncertainty in the knowledge of genetic factors requires us to continue to rely on clinical factors to determine CPSP predisposition. Despite the evidence of association between other genes and chronic pain conditions at this time, any plan to incorporate genotyping information into the ability to predict who will develop chronic pain is premature. In a recent review article, Clarke et al. claim that analyzing patients’ DNA sequences, blood, and salivary pain biomarkers, as well as their analgesic responses to medications, will help us better understand CPSP pathophysiology and help develop predictive algorithms to help establish a patient’s possibility of acquiring CPSP even before surgery. They go on to state that CPSP is likely 50% influenced by genetic determinants. This knowledge will enable us to develop personalized mechanism-based pain treatments. Genetic factors relating to CPSP bear much promise; however, it is clear that significant amounts of work are required before they become of use in clinical practice.
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