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12 Articles in Volume 12, Issue #4
Causes of Postoperative Pain Following Inguinal Hernia Repair: What the Literature Shows
Persistent Postsurgical Pain
Managing Adverse Drug Effects in Pain: Focus on Triptans and NSAIDs
Nonsurgical Treatments for Ankle Arthritis
Opioid Disposal: Dos and Don’ts
Survey Shows More Education About Fibromyalgia Needed Among Healthcare Providers
Anxiety in a Headache Patient: Case Challenge
“Centralized Pain”: A New Consensus Phrase
Tooth Loss in the Chronic Pain Population
When Prescribed Opioids Go Unused
May 2012 Pain Research Updates
May 2012 Letters to the Editor

Persistent Postsurgical Pain

Aggressive perioperative interventions can reduce the intensity of acute postoperative pain, which reduces the risk of a patient developing persistent postoperative pain.

More than 45 million surgical procedures are performed in the United States each year.1 It has been estimated that acute postoperative pain will develop into persistent postoperative pain (PPP) in 10% to 50% of individuals after common operations.2 Since chronic pain can be severe in up to 10% of these patients, PPP represents a major clinical problem—affecting at least 450,000 people each year.

Postsurgical pain is defined as pain lasting more than 3 to 6 months after surgery. The pain differs in quality and location from pain experienced prior to surgery, and is usually associated with iatrogenic neuropathic pain caused by surgical injury to a major peripheral nerve.2 Although all types of surgery can lead to PPP, some surgeries are at higher risk of causing nerve damage, such as inguinal hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery (Table 1). Consequently, surgical techniques that avoid nerve damage should be applied whenever possible.

Despite improved understanding of the process, interpretation of pain signals, and the development of new analgesic techniques,3 undertreatment of postoperative pain continues to be a problem.4 Therefore, it is now recognized that aggressive perioperative interventions can reduce the intensity of acute postoperative pain, which reduces the risk of a patient developing PPP. Genetics may also play a role. The role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain.2 In addition, research is also suggesting that a patient’s emotional make-up can influence his or her risk of developing PPP.5-8 Based on all these factors, it now seems appropriate to apply a multimodal approach to preventing postoperative pain.9,10

This article will review strategies for the identification of patients at risk for PPP, as well as possible treatment strategies.

Mechanisms and Science
Pain is defined by the International Association for the Study of Pain as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”11 It is both a psychological and sensory experience. Research has shown there are multiple brain regions that modulate both pain and emotion.12

Surgery, by nature, involves the cutting of tissues and nerves, which induces the injury response (inflammation, hyperalgesia) and alterations of peripheral and central nervous system (CNS) pain processing (central sensitization), which can lead to chronic pain (Figure 1).2 After peripheral nerve injury, increased sodium-channel (Na) expression on sensitized primary afferent nerves leads to spontaneous activity with increased glutamate release from the nerve endings. This excess of glutamate acts on glutamate receptors (N-methyl-D-aspartate [NMDA], α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA], kainate, and metabotropic glutamate receptors [mGluRs]), thereby triggering intracellular changes. These changes contribute to sustained central sensitization, with increased spontaneous impulse discharges, reduced thresholds, increased response to peripheral stimuli, and expanded receptive fields of central neurons.13

Central sensitization is an amplification of pain signaling in the spinal cord from repeated stimulation from the periphery. Surgery increases synaptic activity in dorsal horn neurons. Humoral signals released from inflamed tissue act on the CNS and intracellular kinases. Within hours, altered gene transcription in the dorsal root ganglion (DRG) of sensory neurons and the spinal cord augment release of excitatory transmitters and reduce inhibitory transmitters. This results in neuronal excitability lasting days. When the noxious stimuli continue, then neuroplastic transformations occur and a positive feedback loop forms. Over time, neurons change structure, function, or chemical profile leading to pain as a disease (see Glossary of Terms).2,14,15

Risk Factors
Patients differ in their response to pain and analgesics partly due to genetics. For example, catechol-O-methyltransferase (COMT) polymorphism is associated with the risk of developing chronic temporomandibular joint pain (TMJ).16Melanocortin-1 receptor gene in red headed/fair skinned persons confers greater female specific kappa-opioid receptor analgesia.17 Patients with complex regional pain syndrome (CRPS) have a high frequency of human leucocyte antigen (HLA)-DQ1 gene. Genetic polymorphism of GTP cyclohydrolase (rate-limiting enzyme for BH4 synthesis and key modulator of peripheral neuropathic pain and inflammatory pain) is associated with less pain following diskectomy.2,18

Psychosocial Factors
Pain is the result of the interaction between biological and psychological variables. Preoperative anxiety and pain are correlated with the development of more postoperative pain.5-8,19 For example, catastrophizing in limb amputees contributes to phantom limb pain.5

Pain Disorders
Fibromyalgia patients have abnormal pain perception with hypersensitivity to painful stimuli and decreased inhibition of descending CNS. In fact, researchers in Germany used functional neuroimaging (fMRI) to study the hypothesis of central pain augmentation in patients with fibromyalgia.20 They confirmed that fibromyalgia patients differ from controls in activation of the fronto-cingulate cortex, supplemental motor areas, and the thalamus over the course of pain stimulation, even during anticipation of pain.

Acute Pain
As noted earlier, studies have shown that the intensity of acute postoperative pain is positively associated with the development of chronic pain (ie, breast surgery, thoracotomy, and inguinal hernia repair).21

Women are at higher risk for postoperative pain, while older patients are at reduced risk of developing chronic pain (some exceptions, ie, postherpetic neuralgia, lumbar spinal stenosis).2,6,22

Type of Surgery
In addition to the type of surgery, surgical technique (and experience of the surgeon) may play a role in the development of postoperative pain (Table 2). Surgery lasting more than 3 hours is associated with an increase in chronic pain and poorer outcomes.22 Patients undergoing surgeries performed by inexperienced surgeons, or in unspecialized units, have more postoperative pain. As noted, neuropathic pain is more common than inflammatory pain, but both can be present in patients with postoperative pain. Differentiation is key for effective strategies to prevent and treat postoperative pain. For example, a continuous inflammatory response, such as after inguinal mesh hernia repair, can occur. Hypoesthesia and pain can also coexist, for example, in postmastectomy, hernia repair, and mandibular osteotomy. Patients undergoing thoracotomy often sustain nerve damage due to the use of rib retractors. Changes in somatosensory evoked potentials and sensory thresholds in the scar are associated with some degree of chronic pain.22

Necessity of Surgery?
Many authorities estimate that 10% to 20% of all surgery is unnecessary.23 During 2009 to 2010, 17.2% of spinal consultations in New York were scheduled for “unnecessary surgery.”24 Chronic pain after surgery is common. If aware of the risks, a patient may forego inappropriate or unnecessary surgery. For example, we know that chronic pain commonly occurs after inguinal hernia repair. Consider watchful waiting, instead of surgery, in those patients with an asymptomatic hernia. Elective or cosmetic procedures, such as breast augmentation and reduction, are associated with a 21% to 50% risk of developing persistent postoperative pain.22 Are patients adequately informed about the risks of such procedures? Abdominal pain due to visceral hyperalgesia results in multiple operations without benefit.10

How to Prevent or Minimize Postsurgical Pain
Preemptive Analgesia
The concept of preemptive analgesia is to initiate an analgesic regimen before the onset of the noxious stimulus (in the case of surgery, the incision) to prevent the development of central sensitization and limit subsequent pain experience. Whether preemptive analgesic interventions are more effective than conventional regimens remains controversial.9,25

Interventions at one or more sites along the pain pathway are recommended to be performed prior to incision. These include infiltration of the incision site with local anesthetics (ie, bupivacaine, lidocaine), performance of regional nerve blocks and epidural or subarachnoid blocks, as well as initiating medications (non-steroidal anti-inflammatory drugs [NSAIDS], NMDA blockers, and opioids).

One retrospective review compared preoperative analgesic interventions with similar postoperative analgesic interventions.26 The researchers retrospectively looked at 66 studies involving 3,261 patients using five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic NMDA receptor antagonists, systemic NSAIDs, and systemic opioids. The researchers found that preemptive administration of epidural analgesia, local anesthetic wound infiltration, and NSAIDs were most effective at reducing the need for postoperative analgesic. Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. Less proof of efficacy was found in the case of systemic NMDA antagonist and opioid administration and the results remain equivocal.26

Preventive Analgesia
Preventive analgesia is considered a more complete intervention than preemptive analgesia. It includes pre-, intra-, and postoperative techniques. There is less focus on the timing of the intervention, with more emphasis on prevention of pathologic pain.27 Both can reduce postsurgical pain long-term (Figure 2).

There is increasing evidence that the efficacy of analgesic agents differs between surgical procedures.28 Therefore, postoperative pain management protocols may be optimized by examining procedure-specific outcomes.29 Surgery-specific nerve blocks—performed preop-, intraop, and postoperatively—and continuous peripheral nerve blocks provide excellent analgesia, safety, opioid-sparing, and improved rehabilitation. For example, the transversus abdominis plane (TAP) block provides excellent analgesia after abdominal hysterectomy, cesarean section, and colonic surgery. The interscalene catheters are typically placed for anesthesia and analgesia after shoulder surgery. Table 3 reviews the types of regional nerve blocks with surgery.

As noted, strategic preoperative delivery of oral or intravenous medications can significantly improve postoperative pain. These agents include NSAIDS, calcium modulators (gabapentin/pregabalin [Lyrica]), and serotonin norepinephrine reuptake inhibitors (venlafaxine, duloxetine [Cymbalta]).30,31 Central sensitization may be minimized if an intervention is done early. Newer analgesics (ie, pregabalin, duloxetine) do not ablate the painful response to noxious stimulus, but normalize hypersensitivity. Neurons change as a result of repeated input causing functional plasticity of the CNS.14

Perioperative infusions of ketamine,32 dexmedetomidine,33 lidocaine,34 and acetaminophen (paracetamol)35 have all been shown to improve postoperative outcomes. Postoperative treatments, such as NSAIDs, gabapentin, pregabalin, capsaicin patch, IV paracetamol, IV ibuprofen, glucocorticoids (dexamethasone 0.2 mg/kg), IV ketamine infusion, IV and oral opioids, TENS, and acupuncture all may help prevent acute pain from becoming chronic. Table 4 reviews newer agents and their mechanisms of action.2,36

As noted, research now suggests that a multimodal approach tailored to the needs of the individual and surgery type is most effective for preventing and treating postoperative pain. The goal is to use a combination of analgesics/treatments with different mechanisms of action, acting on different sites in the central and peripheral nervous system. Therapy is directed to reduce adverse effects and minimize the need for opioids, all to facilitate discharge and rehabilitation. Treatment should be targeted at the progression of mechanisms, not just the disturbances in sensation. Most cases of postsurgical chronic pain are neuropathic. Remember that neuropathic pain involves the entire neuroaxis (peripheral and central) such that centralization of pain occurs.2,36-40

Case Examples
The following three cases demonstrate the pros and cons of preventative analgesia.

Left Bunionectomy
A 43-year-old mother underwent an elective left bunionectomy by a community podiatrist. She had no significant past medical history aside from smoking. Her left bunion was asymptomatic at rest, but caused moderate pain when wearing heels. There was no pre- or intraoperative pain management.

Immediately after surgery, the patient reported exquisite pain in the lateral/dorsal aspect of the foot. Six months later, she complained of 9 out of 10 pain on the visual analog scale with weight bearing. Her foot had significant allodynia, erythema, and increased warmth on examination. She could not wear any closed shoes.

The patient failed various pain medications due to drug sensitivity, including gabapentin, tramadol, and hydrocodone/acetaminophen. Continuous sciatic nerve blocks (popliteal), performed under ultrasound guidance, and lumbar sympathetic blocks were of limited benefit. The patient, who only spoke Vietnamese, had a fear of procedures and cultural beliefs. Last update: she was applying for disability insurance and in litigation with the surgeon.

Mastectomy Patient
A 38-year-old married woman with a strong family history of breast cancer had a questionable breast biopsy in 2009. She underwent a prophylactic bilateral mastectomy later that year. The surgeon specialized in breast surgery and was highly skilled. As part of her pain management plan, the patient received 60 mg of prednisone pre- and postoperatively and had excellent anesthesia care. The mastectomy was done without lymph node dissection and without reconstruction or implants. She reported no pain after surgery and has had none since; only some numbness along the margin of scar and right inner axilla. She returned to ballroom dancing 2 months after surgery and is doing well. Research has shown a greater incidence of postmastectomy pain after mastectomy with reconstruction and/or breast augmentation, compared to mastectomy alone. Pain in the axilla and upper arm are related to injury of the intercostal brachial nerve during lymph node dissection. Numbness and dysesthesias are common post mastectomy.22

Injured Security Guard
The ongoing conflict in Afghanistan continues to generate a large number of complex trauma injuries and provides unique challenges to military anesthetists working in the austere battlefield hospital environment. The Department of Defense has had a high success rate using multimodal analgesic treatments. This includes ultrasound-guided continuous peripheral nerve blocks (CPNB) for major extremity and abdominal trauma. Multiple benefits include earlier recovery, excellent analgesia, and minimal postoperative morphine requirements despite issues like massive blood transfusion and coagulopathy.41,42

Here is an example of a 28-year-old male security guard who sustained a blast injury to his right lower leg in 2008 in Iraq. He received multiple orthopedic surgeries in the United States (ie, Walter Reed National Military Medical Center) with CPNB anesthesia of the popliteal/sciatic nerve under ultrasound guidance. The patient was walking and had minimal pain several years later with duloxetine, pregabalin, and topical lidocaine 5% patches.

Chronic pain after surgery is a significant problem that reduces the quality of life of patients. It is important to identify patients at risk of developing this syndrome. Iatrogenic neuropathic pain is a common cause of PPP. Treatment should be targeted at the progression of mechanisms leading to neuro-degeneration. Improving the management of acute intra- and postoperative pain and good surgical techniques are some helpful strategies. Furthermore, we need to educate patients wanting surgery for reasons other than illness or disability of the risk of the development of PPP.


Last updated on: June 19, 2017
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