Persistent Postsurgical Pain – Practical Pain Management
Surgery is often counterproductive for chronic pain, so beware!
More than 45 million surgical procedures are performed in the United States each year. It has been estimated that acute postoperative pain will develop into persistent postoperative pain (PPP) in 10% to 50% of individuals after common operations.
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.
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, undertreatment of postoperative pain continues to be a problem.
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.
In addition, research is also suggesting that a patient’s emotional make-up can influence his or her risk of developing PPP.
Based on all these factors, it now seems appropriate to apply a multimodal approach to preventing postoperative pain
Mechanisms and Science
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).
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.
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).
Patients differ in their response to pain and analgesics partly due to genetics.
- catechol-O-methyltransferase (COMT) polymorphism is associated with the risk of developing chronic temporomandibular joint pain (TMJ).
- Melanocortin-1 receptor gene in red headed/fair skinned persons confers greater female specific kappa-opioid receptor analgesia.
- Patients with complex regional pain syndrome (CRPS) have a high frequency of human leucocyte antigen (HLA)-DQ1 gene.
Preoperative anxiety and pain are correlated with the development of more postoperative pain
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.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.
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)
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).
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.
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.
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.
Necessity of Surgery?
Many authorities estimate that 10% to 20% of all surgery is unnecessary.
Chronic pain after surgery is common. If aware of the risks, a patient may forego inappropriate or unnecessary surgery.
Elective or cosmetic procedures, such as breast augmentation and reduction, are associated with a 21% to 50% risk of developing persistent postoperative pain.
Are patients adequately informed about the risks of such procedures? Abdominal pain due to visceral hyperalgesia results in multiple operations without benefit.
How to Prevent or Minimize Postsurgical Pain
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.
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).
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.
Preventive analgesia is considered a more complete intervention than preemptive analgesia. It includes pre-, intra-, and postoperative techniques.
There is increasing evidence that the efficacy of analgesic agents differs between surgical procedures.
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
As noted, strategic preoperative delivery of oral or intravenous medications can significantly improve postoperative pain. These agents include
- calcium modulators (gabapentin/pregabalin [Lyrica]), and
- serotonin norepinephrine reuptake inhibitors (venlafaxine, duloxetine [Cymbalta]).
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.
Perioperative infusions of
- lidocaine, and
- acetaminophen (paracetamol)
have all been shown to improve postoperative outcomes.
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.
The following three cases demonstrate the pros and cons of preventative analgesia.