Revista El Dolor 59 | Julio 2013 - Año 23 | Revisiones Bibliográficas

Correspondencia: Dr. Javier Quilodrán Peredo Unidad de Cuidados Paliativos, Hospital San Luis de Buin-Paine. Unidad del Dolor y Cuidados Paliativos, Oncomed. quiloper@hotmail.com

Background: Chronic postoperative pain (CPP) is an important health problem. This is a narrative review of etiologies, mechanisms, risk factors, means of reducing the risk, and treatment of chronic postoperative pain.
Methods: This is a topical review based on a focused literature review  and   personal   clinical   experience and research efforts on chronic pain after surgical interventions.
Results: CPP is defined as new pain in the area of surgery that lasts more than 3-6 months after the operation, is clearly related to tissue and nerve injuries during the operation and cannot be explained by other etiologies.
The overall prevalence is that 20-40% have some pain and discomfort for a few weeks, 10% have moderate pain that cannot be neglected for a few months, about 1% develop debilitating CPP.
CPP is caused by nerve and tissue injury and abnormal reactions to such injury.  Only  those  who  have  pre- and peri-operative risk factors determined in part by genetic makeup, reinforced by abnormal pain modulating mechanisms,  having  chronic   pain   in  other   part(s) of the body, having psychological stress factors and catastrophizing thoughts and anxiety, having severe acute pain during and immediately after surgery, chemotherapy or radiation after cancer surgery, and being younger rather than elderly. Risks of CPP can be estimated by a simple scoring system with approximate risk prediction determined by the number and degree of preoperative  risk factors.
A number of procedures and drugs can ameliorate these risk factors: Regional and local anesthetic techniques when appropriate, anti-hyperalgesic drugs with nitrous
 

oxide, glucocorticoids, gabapentinoids, pregabalin more than gabapentin, possibly tricyclic antidepressant, and infusions of lidocaine and ketamine. Important is that the surgeon uses nerve-sparing techniques and operates as “atraumatic” as possible.
Fast-track and vigorous  mobilization  and  rehabilitation of functions after surgery is made possible by expert analgesic  and  anti-hyperalgesic  drugs. Mot  important is to NOT do unnecessary operations such as cosmetic breast enlargement and meniscectomies for atraumatic knee-meniscus degeneration.
Acute Pain Service, extended to an  Acute  Pain-Follow-  up  Service  is  mandatory  to  make        postoperative pain management optimal and to follow up and treat adequately those unfortunate patients who do develop CCP. Conclusions   and   implications: CPP  is        a common complication  to    well indicated surgery of any type, sometimes developing into a debilitating pain condition. Therefore, evaluation of risk factors before surgery and optimal management during and after surgery is highly important for the patient’s GP, his/her surgeon and anesthesiologist.    Multidisciplinary    pain    management clinics  are  necessary  for  those   unfortunate  1%  of  all surgical patients who develop complex, chronic postoperative pain.

Keywords: Chronic postoperative pain,  risk  factors, neuropathic pain, peripheral  hyperalgesia, secondary hyperalgesia, antihyperalgesic drugs, epidural analgesic, lidocaine, pregabalin, acute pain  service, acute-pain follow-up service, pain clinic.
 

Long-lasting new pain after an operation is a common, sometimes a debilitating consequence of surgery. We know some factors that increase the risk of developing chronic postoperative pain (CPP). The patients’ GP, surgeon, and anesthesiologist must focus on these risks and prioritize efforts to reduce their effects on the postoperative course.
As Rashiq and Dick pointed out recently (1), the earliest practitioners of anesthesia could only pray that their patients survived anesthesia. Later generations, when anesthesia developed into a very safe practice, focused on reducing immediate complications after anesthesia and surgery. They established effective prophylaxis and treatment of acute pain, nausea, vomiting, and venous thromboembolism (2)]. The present generations of anesthesiologists, in collaboration with surgeons, are taking on the challenge of reducing long-term 

complications of surgery: Reducing the risk of new, long- lasting, and severe pain after surgery.
What is chronic postoperative pain (CPP)?
CPP is pain in the area of surgery that was not there before  the operation, and it lasts more than 3-6 months after surgery. CPP is not a continuation of pain that the patient had in that area before surgery. About ¾ of chronic postoperative pain is nerve-injury pain, i.e. neuropathic pain (3).

Etiology and mechanisms of pathogenesis of chronic postoperative pain.
The pain is caused by nerve and tissue injury. However,  nerve injury alone is not sufficient for new pain after surgery to become chronic postoperative pain – other contributing factors and abnormal reactions to the injury are necessary (4). This is clearly demonstrated by the fact that there are many with evidence of nerve damage (hypo- and/or hyper-aesthesia around the scar) who do not have chronic postoperative pain (4,5).
A series of events and reactions to the tissue and nerve injury occurs at many levels of the CNS:
1.    Peripheral nociceptive nerve endings become hypersensitive and “silent nociceptors“ wake up due to  the many pronociceptive components, e.g. prostaglandins and cytokines, in the “inflammatory soup” in the injured tissue. This causes primary hyperalgesia.
2.    Secondary hyperalgesia is due to central hypersensitivity reactions in the dorsal horn of the spinal cord and at the brain stem.
3.    In the mid-brain – thalamic area negative emotional reactions to incoming nociceptive signals occur.
4.    In the cortex cerebri, cognitive modulation or cognitive misinterpretations of the tissue injury occurs, dampening or aggravating the conscious experience of pain.
5.    In addition, there are descending inhibiting and facilitating signals from the brain and brainstem to the dorsal horn of the spinal cord. These can again reduce     or increase transmission to higher centra in the CNS of incoming nociceptive signals from the injured nerves and tissues (4).
This series of events happens always in all patients having surgery. However, it is only persons with additional risk factors and those who have a genetic makeup that allows or facilitates exaggerated and pathological reactions to nerve and tissue injuries, who will eventually end up with a painful condition that lasts for a long time: i.e. only these unfortunate few patients develop chronic,  severe and debilitating postoperative pain (4,6).
Prevalence of chronic pain after surgery
There are several cross-sectional prevalence studies  estimating occurrence of long lasting pain after different  types of surgery. CPP can follow any type of surgery, but it   is more frequent after surgery where tissue trauma is large  and where the surgeon cannot avoid injuring nerves (3,4).     In the large Tromsø-health survey in Norway, ongoing for more than two decades, pain-issues were included in 2007-8 (5). 13 000 respondents were examined for aspects of pain sensitivity and interviewed about their past health history.
 

3000 had had surgery during the last 3 years, and 2045 of these persons could be examined in detail: 60% had not had any new pain after their surgery, 40% answered that they did have persistent pain in the area of surgery, 7% had severe pain, 20% had moderate pain, and 13% had only mild pain (5). The round numbers from cross-sectional and prospective studies are approximately like this:
1.    Among 100 patients who have had surgery  20-40  will have some (new) pain and discomfort in the area of surgery that lasts for several weeks-months after surgery.
2.    About 10 will have moderately intense pain that lasts for several months, and the pain is severe enough that the patient cannot neglect the symptoms, but they are usually able to perform the activities of normal life.
3.    However, 1 of 100 surgical patients will unfortunately have severe, disabling pain in the area of surgery that becomes a major problem for every aspects of the patient’s life.

Known preoperative risk factors for having chronic postoperative pain
1.    Pain in the area of surgery before the operation (4).
2.    Chronic pain outside the surgical area before surgery are well-documented risk factors, e.g. low-back pain, migraine, neck pain, and any type of widespread pain (4).
3.    Patients who have had a stressful life situation during the months before surgery are at higher risk, and so are patients who have catastrophizing thoughts about the surgery they are about to undergo (7).
4.    Younger women have higher risk than older women who have surgery for cancer of the breast (10). Younger men having inguinal hernia repair are at higher risk than elderly men (28). Women are at higher risk than men.
5.    Several genetic variants appear to confer higher risks than the general population (6). It is well documented in twin-studies that tendency to have chronic wide-spread pain, headache, low-back  pain,  migraine,  neck  pain,  and other types of chronic pain have 30-50% heritable causes (8).

Known risk factors during surgery
Clearly, the degree of tissue and nerve injury is important. Nerve-sparing techniques, e.g. laparoscopy  compared with open inguinal hernia operations decrease  the  risk (9). Lymph node dissection has threefold  higher  risk  than sentinel biopsy for chronic pain after breast cancer surgery (10).
Known factors immediately after surgery
1.    Inadequate acute pain management and severe postoperative acute pain during the first few days after surgery markedly increases the risk (4, 11).
2.    Chemotherapy and radiation therapy after cancer surgery doubles the risk (10).
3.    Immobilization aggravates the risk of CPP (4).

What can we do to reduce the risk of chronic pain after surgery?
During anesthesia, the following procedures and drugs are documented to reduce the risk of chronic pain after surgery,  as documented in some studies and some types of surgery.

patients must be given special attention and monitoring for up to several weeks after surgery. Patients who have abnormal pain intensities and clearly have components of neuropathic pain 6 weeks after surgery, have a much increased risk of having such pain also 3 and 6 months after surgery (18).

Acute Pain Service (APS) and Acute Pain Follow-up Service (or Sub-acute Pain Service)
All hospitals doing surgery should have an Acute Pain Service team (APS) as described by Breivik et al  (22).  Recently  these APS teams are being extending into Acute Pain- follow-up teams [Michele Curatolo and Eija Kalso, personal communications]. They continue to have special attention on patients who have the recognized risk factors and keep on having abnormal pain and sensory findings: Hypo-phenomena (hypo-aesthesia for pinprick, cold  or  warm  stimuli,  cotton or brush-stimuli) as well as hyper-phenomena (mechanical, dynamic allodynia, or cold- and/ or warm-allodynia, temporal summation) in the weeks following surgery (18, 29). Those who have clear symptoms and signs of neuropathic pain at 6 weeks, frequently have such pain also 3 and 6 months after surgery (18).
It is more likely that we can influence the long-term outcome if we treat and manage the pain conditions of these patients aggressively early on with drugs and procedures that are documented to have beneficial effects on neuropathic pain.    If patients have been neglected, or they may even have been told by ignorant health care providers that the pain will soon subside naturally, they may have  a  high  risk  of  suffering for many months and years after surgery, from a treatment- resistant pain that they did not have before that operation.

What is the long-term prognosis of chronic postoperative pain?
There is one long-term follow-up study of a large number of patients with chronic pain after inguinal hernia repair (28):    In a national registry of inguinal hernia repair in Sweden comprising more than 140.000 patients since 1992, a survey was undertaken by Professor Torsten Gord’s Pain Centre at Uppsala University Hospital. They surveyed  patients  living in the Uppsala County in Sweden. From data of 2834 hernia repairs (in 2583 patients), they were able to estimate a decline by 50% in pain during a bit more than 6 years. These are important observations, and we can tell the patients with some confidence that with time, their pain will gradually decrease. However, if re-operations are done, in order to explore and “look for a cause of the pain” in the scar, chances are that the patient will have even worse pain after such a re-operation (28). There are occasional indications for surgery, when there are convincing signs that a localized peripheral nerve entrapment in scar tissue contribute to the pain. However, expert surgeons in collaboration with clinical neurophysiologists [Henrik Kehlet, personal information] should do such re-operations.

Most important is to avoid all unnecessary surgery. This may seem like an unnecessary statement. However, there are many cases reported in the literature of patients ending   up with a disabling chronic postoperative pain condition after surgery that was not indicated. A striking example is the large numbers of cosmetic breast augmentation operations being done in affluent societies: In Norway about 5% of young
 

women have silicone implants into their breast – for purely self-esteem-increasing purposes. That effect is at best only short lasting. Unfortunately, 20-40% have pain and discomfort 3 years later, 1-2% have severe and disabling pain after this completely unnecessary type of surgery (18, 29). If rumors  are correct, in Brazil parents give their teenage daughters the price of such a cosmetic operation as a birthday gift!
A similar situations occurs with patients without osteoarthritis but with symptoms of a degenerative medial meniscus tear: In a double blind trial in Finland published in 2013 the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure (30).