Surgical Pain – Post-Operative
Aside from concerns regarding impairment or loss of function after surgery, most people’s primary concern for surgery revolves around pain and it’s effective management. This is especially true for patients who already suffer from chronic pain. This population has been shown to be hypersensitive to pain and require higher doses of opioids to manage their post-operative pain.
Another common and important concern is the potential for surgery to result in a new or worsened chronic pain. The following is directed at addressing these concerns and what can be done to improve outcomes.
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Surgical Pain – Post-Operative
Planning for Management of Post-Operative Pain: Out-Patient
When you plan to have surgery, including orthopedic or dental procedures, it is best to plan ahead. These special circumstances require appropriate communication between both you and the surgeon or dentist as well as your pain management physician.
There are medical and pharmacologic implications that are significant in this situation. Most importantly, the anesthesiologist and surgeon must be completely aware of your current medications in order to safely dose anesthetics during the surgical procedure and to be able to more accurately predict your post-operative pain medication needs. Without knowing your tolerance and experience with pain medications, the surgeon may under-dose your pain medications and provide inadequate relief of your pain.
The regulations governing patients in the chronic opioid pain management setting may restrict patients to being prescribed medications only by their pain management physician unless alternative plans are made. Because surgeons may be uncomfortable or lack the knowledge for prescribing post-operative pain medications in this setting, it is best to initiate communication with both your surgeon and your pain management physician well before surgery. First, notify your pain management physician of any upcoming surgery to discuss options.
Your pain management physician may then arrange for your surgeon to take over responsibility for managing your post-operative pain, including writing your pain prescriptions for the days or weeks following your surgery. When the surgeon feels the time is appropriate, he can then provide your pain management physician with a final post-operative report of your condition and transfer back the responsibility for chronic pain management as indicated to the pain management physician. The advantages to having the surgeon manage post-op pain include the surgeon’s intimate knowledge of the pain expected to be associated with a certain procedure, usual close post-op follow-up appointments and the potential for restricted travel in the post-op period that limit access to your pain management physician.
When a surgical procedure is not expected to restrict travel or access to your pain management physician, the post-op pain can be managed directly by the pain management physician. The advantage of this option is that it allows for continuity of care from the physician with the most intimate knowledge of your pain and your history of pain medications.
Buprenorphine (Butrans, Belbuca, Suboxone, Zubsolv, Bunavail)
Because of the special pharmacologic characteristics of buprenorphine, special attention must be taken to plan for post-operative pain management for those patients taking buprenorphine.
Unplanned and Emergency Surgery/Surgical Procedures
Even when the circumstances are such that it is not possible to advise your pain management physician before a surgery or procedure, it is still the responsibility of the patient to fully inform the surgeon of their chronic pain management circumstances.
Please inform your pain management physician as soon as you are able to do so when planning any surgical or dental procedure so that he can assist you in meeting your pain management needs. Failure to do so may result in both medical and regulatory pitfalls that would otherwise be easily avoided.
Special Considerations in the Management of Post-Operative Pain: In-Hospital
Pain has an adverse effect on postoperative recovery beyond the simple element of suffering, including exposure to additional medications and their potential complications that could prolonging the time to recovery and extend the length of hospital stay. Research is focusing on understanding the different variables that contribute to post-operative pain. One variable, of course, is the type of surgery. For example, it has been reported that the pain occurring after total knee arthroplasty (TKA) is more painful than that of any other orthopedic surgery, including total hip arthroplasty.
Chronic pain after thoracic surgery has been reported as high as 25–60%. Chronic chest wall pain in patients who have had mastectomies is increasingly recognized as a common and problematic complication of these surgeries (See Post-Mastectomy Pain). Approximately 14% of patients undergoing laparoscopic herniorrhaphy develop chronic pain. The prevalence of phantom pain following surgical amputation is high, occuring in 79% of cases. There is even a postsurgery fatigue syndrome that is becoming better recognized.
Even when surgery is performed to reduce pain, chronic pain can persist or worsen despite the surgery. With surgery for low back pain, there is a 5%–36% recurrence rate of back or leg pain 2 years after discectomy for disc herniation. In addition, it has been reported that 29% of patients had the same or increased pain 1 year after surgical laminectomy for lumbar stenosis secondary to degenerative changes.
The reason why some patients develop persisting pain and with others their pain resolves is still unknown. Data from research clearly suggest a genetic predisposition for those who develop chronic pain following a precipitating incident. Twins studies show a heritable component to the risk of developing persistent pain of up to 60%. Part of this risk is very likely to be epigenetic as well (see below).
The use of opioids during surgery may effect post-operative pain and post-operative pain management can result in adverse effects, such as sedation, nausea and vomiting, urinary retention, ileus (interference with bowel function), and respiratory depression. In an effort to reduce these complications, multimodal analgesia, i.e., the use of more than one analgesic modality to achieve effective pain control while reducing opioid-related side effects, has become the cornerstone of enhanced recovery.
Understanding the mechanisms of surgery-related pain is the first step in reducing it and potentially avoiding the transition from acute, post-operative pain to becoming chronic.
Mechanisms of Pain Associated with Surgery
Central and Peripheral Nerve Sensitization: Related to Surgery
Following surgery, the intense influx of acute pain signals from peripheral nerves related to tissue trauma can trigger a magnification of pain through peripheral and central nerve sensitization, in which the excitability and responsiveness of nerves is increased. This is especially true in the dorsal horn of the spinal cord where peripheral nerves synapse (interact) with central nerves and pain transmission is enhanced.
Central and Peripheral Nerve Sensitization: Related to Chronic Pain
It has been well established that when people experience chronic pain, whether it be related to chronic headaches, injuries such as neck and low back pain, or medical conditions including fibromyalgia, menstrual pain or irritable bowel syndrome, they develop peripheral and, especially, central sensitization in the spinal cord and brain. This contributes to a magnified experience of pain (hyperalgesia), including acute pain unrelated to their chronic pain condition. The result of central sensitization contributes to other abnormal pain responses such as experiencing pain with non-painful stimuli (allodynia) and spread of hypersensitivity beyond the injured tissue. Patients with chronic pain frequently experience post-operative pain more severely and require higher doses of opioids to control that pain compared with patients without chronic pain.
Magnified Pain (Hyperalgesia): Related to Use of Opioids (OIH)
There is a growing body of research demonstrating that both acute and chronic use of opioids may contribute to a heightened or magnified experience of pain termed opioid-induced hyperalgesia (OIH). The incidence of OIH with acute, post-operative pain has been well demonstrated with the use of remifentanil, an opioid used during anesthesia for surgery. Post-operatively, patients receiving remifentanil experience magnified pain related to their surgery, subsequently requiring higher doses of opioids to control pain.
There is limited research that also suggests that long-term use of opioids for chronic pain can also lead to hyperalgesia. This has been demonstrated mostly related to experimental pain models evaluating pain from exposure to cold or heat. Whether these findings are clinically relevant remains to be established.
Transitioning Acute Post-Op Pain to Becoming Chronic Pain – Epigenetics
One of the worst outcomes of acute, post-operative pain is having that pain evolve into chronic pain. Understanding the mechanisms of how acute pain becomes chronic rather than healing and resolving is an important riddle that eludes full understanding.
Under persistent pain conditions cells processing pain signaling, i.e., nociceptors (pain receptors) in the peripheral nervous system and neurons/glia in the central nervous system, become sensitized in response to various stimuli. This increased sensitivity is accompanied by functional and structural changes (plasticity). Multiple mechanisms are likely responsible for these changes.
One area of study that is beginning to shed light on this process is the study of “epigenetics,” which refers to changes in a chromosome (DNA) that affect gene activity and expression. People inherit genes that determine personal characteristics including such as eye color and height or physiologic processes such as how medications are metabolized or how effective they are. The expression of these genes can be modified, for example by being amplified, suppressed or turned on or off. It is believed that epigenetic modification of genes may at least be in part responsible for transitioning acute pain, such as post-operative pain, to becoming chronic and persisting beyond apparent tissue healing. Understanding this process may lead to avoiding the evolution of chronic pain.
Medications can impact epigenetic change, including opioids. Both the developmental expression of the μ opioid receptor, and pathological hyperalgesia are mediated, at least in part, by epigenetic mechanisms. In general, opiates seem to increase global DNA methylation levels, a mechanism associated with hyperalgesia. This is in contrast to another group of drugs used in surgery – local anaesthetics. Local anaesthetics such as lidocaine appear to induce DNA demethylation, and may thereby protect against the development of hyperalgesia. Clinically, some studies have demonstrated a reduction of hyperalgesia and inflammation post-operatively vis epigenetic mechanisms with local anaesthetics.
Of major significance is that epigenetic modification can be inherited, passed on to the next and future generations. In other words, an environmentally-induced change in DNA expression can affect not just the person but their children and grandchildren. In animal studies of stress-induced intestinal pain hypersensitivity, epigenetic changes associated with experimental irritable bowel disease could still be detected in offspring two generations later. It is believed also that during pregnancy exposure to certain medications or drugs can precipitate epigenetic changes that are then passed on to the fetus.
Reducing Post-Operative Pain
A great deal of research is being perfomed in an effort to better understand more about how acute pain becomes chronic. Of particular interest in recent research is exploring ways to reduce the post-operative pain associated with surgical procedures, including orthopedic and abdominal surgeries as well as others.
In an effort to reduce both acute post-operative pain and the development of chronic post-operative pain, studies are ongoing to identify both pharmacologic and non-pharmacologic means of doing so. Pharmacologic agents that are being explored include gabapentin and pregabalin, tramadol, NSAIDs, clonidine, ketamine, orphenadrine and nefopam (a non-opioid analgesic not available in the U.S.). Non-pharmacologic methods include acupuncture, relaxation therapy, music therapy, hypnosis and transcutaneous nerve stimulation (TENS) as part of multi-modal approaches of reducing post-operative pain. It has been shown that treating pain using different forms of treatment including multiple medictions with different mechanisms of action offers the most effective means of controlling pain while at the same time reducing the need for opioids and limiting the evolution of chronic pain.
Gabapentin (Neurontin) & Pregabalin (Lyrica)
In multiple 2016 reviews of studies evaluating post-operative pain after total knee and total hip arthroplasties (replacements), surgical procedures in which parts of the joints are replaced with artificial parts (prostheses), it was shown that the need for opioids for post-operative pain was reduced when gabapentin was used. The pruritis (itching) associated with the post-operative opioids was also lessened. The dose of gabapentin ranged from 300 mg to 1200 mg before surgery and sometimes right after surgery, though an optimal dose was not identified. Despite the reduction in need for opioids for pain, the pain scores were not significantly different.
A 2011 study evaluating post-operative pain after lumbars discectomies and laminectomies revealed similar results with reductions in post-operative pain, use of opioids and pruritis when gabapentin (1200 mg) and Lyrica (300 mg) were provided in the 24 hours preoperatively.
Additional studies evaluating post-operative pain with abdominal and vaginal hysterectiomies, gall bladder surgery, tonsillectomies and breast surgery also described similar benefts of gabapentin.
The optimal dosages of the two drugs for postoperative pain are still controversial. In postoperative pain studies, gabapentin doses ranged from 300 mg to 1,200 mg, and those for pregabalin ranged from 50 mg to 300 mg. Regardless of their dosages, the adverse effects of both drugs were found to be similar.
Reduction in Chronic Post-Operative Pain
While fewer studies are available, a 2012 review of the literature concluded that perioperative treatment with gabapentin and pregabalin are effective in reducing the incidence of chronic postsurgical pain (CPSP), defined as pain lasting more than 2 months.
Pregabalin 300 mg day−1 and gabapentin 1,200 mg day−1 showed equivalent analgesic, opioid- sparing and adverse effects as well as patient satisfaction.
An important mechanism in hyperalgesia involves the N-methyl-D-aspartate (NMDA) receptor, known for its major role in nerve plasticity (modification), and glutamate, the neurotransmitter that activates it. Spinal nerves experimentally exposed to remifentanil show increased NMDA receptor activity. Animal studies show that NMDA antagonists that block NMDA can abolish hyperalgesia, supporting the rationale of using ketamine, an NMDA antagonist, in the management of post-operative pain especially when remifentanil is used during anesthesia. While the use of ketamine intravenously is limited to in-hospital treatment by anesthesiologists, topical ketamine can be prescribed and may be useful in post-op pain.
Orphenadrine (Norflex), a medication used for muscle spasm, also has weak NMDA activity and may offer benefit in reducing the development of hyperalgesia. Memantine (Namenda), a medication used for Alzheimer dementia, has NMDA activity and there is growing evidence suggesting that memantine may be useful in reducing neuropathic (nerve) pain. Memantine has been studied in certain subgroups of pain patients including a trial showing the benefit of a combination of morphine and memantine in patients with complex regional pain syndrome (CRPS).
Magnesium Sulfate (MgSO4), given intravenously, has been shown in multiple recent studies to reduce post-operative pain and allow for reduced dosing of opioids. In a March 2017 study, investigators concluded that MgSO4 appeared to increase the analgesic potency of morphine. While the mechanism of this action has not been clearly defined, it is consistent with NMDA antagonist activity. A 2013 meta-analysis concluded that peri-operative intravenous magnesium reduced opioid needs and pain scores in the first 24 hours postoperatively, without any reported serious adverse effects.
Over-the-counter NMDA antagonists include magnesium (epsom salts) and dextromethorphan (DM), a common cough suppressant used in Delsym, Robitussin DM and others. While the NMDA activity of these medications may be low, it is often the case in the field of medicine that the amount of a medication used to prevent a condition is less than that required to reverse a condition. Unfortunately studies are lacking but, generally speaking, the safety of these medications is well established.
Choice of post-operative opioid
Another consideration that should be emphasized is the choice of post-operative opioid. Some opioids have inherent NMDA activity over and above their typical analgesic action on opioid receptors. These opioids may offer an advantage over traditionally used opioids such as hydrocodone (Norco), oxycodone (Percocet), hydromophone (Dilaudid) and morphine. Opioids with NMDA activity include tramadol (Ultram), methadone and levorphanol, the opioid with the highest NMDA activity.
The Final Word on Reducing Post-Operative Pain
It is evident that there is much to learn about reducing post-operative pain and preventing the development of chronic pain. The medications described above remain in experimental phases but do offer potential benefit. It is also expected that future studies of epigenetic mechanisms may produce novel and effective analgesic drugs.
One underlying principle remains: pain is magnified by stress. There are many measures one can embrace to reduce stress both during the pre-operative and the post-operative time frame. These measures include nutritional and behavioral options. It is strongly advised to explore these areas on other pages of this web site:
Preventing Pain Related to Surgery – Overviews
- perioperative-pain-management- 2007 pubmed-ncbi
- optimizing-pain-management-to-facilitate-enhanced-recovery-after-surgery-pathways 2015 -pubmed-ncbi
- Post-operative Opioid-Induced Hyperalgesia – ICM Case Summaries – 2016
- The Complexity Model – A Novel Approach to Improve Chronic Pain Care – 2014
Preventing Pain Related to Surgery – Genetica
Preventing Pain Related to Surgery – Epigenetics
- Could targeting epigenetic processes relieve chronic pain states? – PubMed – NCBI
- Telomeres and epigenetics – Potential relevance to chronic pain – 2012
- Epigenetics of chronic pain after thoracic surgery. – PubMed – NCBI
Preventing Pain Related to Surgery – Gabapentin & Pregabalin
- Do surgical patients benefit from perioperative gabapentin:pregabalin? A systematic review of efficacy and safety. – PubMed – NCBI
- Perioperative administration of gabapentin 1,200 mg day−1 and pregabalin 300 mg day−1 for pain following lumbar laminectomy and discectomy – 2011
- Preemptive use of gabapentin in abdominal hysterectomy: a systematic review and meta-analysis. – PubMed – NCBI
- The Effect of Gabapentin on Acute Postoperative Pain in Patients Undergoing Total Knee Arthroplasty – 2016
- The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. – PubMed – NCBI
- The use of gabapentin in the management of postoperative pain after total hip arthroplasty – 2016
- The use of gabapentin in the management of postoperative pain after total knee arthroplasty – 2016
- Use of gabapentin for perioperative pain control – A meta-analysis – 2007
- The efficacy of gabapentin:pregabalin in improving pain after tonsillectomy: A meta-analysis. – PubMed – NCBI
- Effects of gabapentin on postoperative pain, nausea and vomiting after abdominal hysterectomy: a double blind randomized clinical trial. – PubMed – NCBI
- Gabapentin and postoperative pain – a systematic review of randomized controlled trials 2006 – PubMed Health
- Preoperative Preemptive Drug Administration for Acute Postoperative Pain – A Systematic Review And Meta-Analysis – 2016
- perioperative-pain-management- 2007 pubmed-ncbi
- optimizing-pain-management-to-facilitate-enhanced-recovery-after-surgery-pathways 2015 -pubmed-ncbi
- The Anti-Allodynic Gabapentinoids – Myths, Paradoxes, and Acute Effects – 2016
Preventing Pain Related to Surgery – Ketamine
- Role of Ketamine in Acute Postoperative Pain Management – A Narrative Review – 2015
- Perioperative ketamine for acute postoperative pain. – PubMed – NCBI
Preventing Pain Related to Surgery – Magnesium
- Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. – PubMed – NCBI
- Peri-operative intravenous administration of magnesium sulphate and postoperative pain – a meta-analysis – 2013
- Effect of magnesium sulfate on morphine activity retention to control pain after herniorrhaphy. – PubMed – NCBI
Preventing Pain Related to Surgery – Nefopam
Emphasis on Education
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