Accurate Education – Surgical Pain, Post-Operative

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.



Considering Spine Surgery?

Central Sensitization

Opioid-Induced Hyperalgesia (OIH)

Neurobiology of Pain


see also:

Gabapentin & Lyrica

Palmitoylethanolamide (PEA)





Definitions and Terms Related to Pain


Key to Links:

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“An ounce of prevention is worth a pound of cure”

– Benjamin Franklin

Surgical Pain – Post-Operative


Out-Patient: Planning for Management of Post-Operative Pain

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.


Option 1

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.


Option 2

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.

See: Buprenorphine – Emergency & Surgical Pain Management



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 could otherwise be easily avoided.


In-Patient: Special Considerations in the Management of Post-Operative Pain

Pain has an adverse effect on post-operative 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.


The occurrence of chronic pain after surgerycannot be predicted by the kind of surgical procedure performed. Furthermore, it has been estimated that chronic postsurgical pain occurs in 1 of every 10 surgical procedures and it becomes an unbearable condition in 1 of every 100 surgeries.


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.


Postoperative Cognitive Dysfunction (PCD)

Postoperative cognitive dysfunction (PCD), or impaired thought processing, is often seen in the elderly after surgery and hospitalization. Not unlike circumstances surrounding traumatic brain injury (TBI), a state of neuroinflammation can be initiated by surgical trauma even outside of the brain and central nervous system. Inflammatory mediators released in the surgical site can enter the nervous system and damage synapses and neurons. This has been proposed as a critical component of surgery-induced PCD. As with TBI, cerebral mast cells have been suggested to contribute to postoperative cognitive dysfunction and pain after surgical procedure-mediated neuroinflammation by promoting breakdown of the integrity of the blood-brain barrier (BBB). In addition, astrocyte participate in surgery-induced cognitive dysfunction and neuroinflammation via evoking microglia activation.


It follows that treatments directed at neuroinflammation for the reduction of post-operative pain may also reduce the incidence and/or severity of postoperative cognitive dysfunction (see below).

See: Traumatic Brain Injury (TBI)


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.

See Central Sensitization


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.

See Central Sensitization


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.

See Opioid-Induced Hyperalgesia (OIH)


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.


Multi-modal Approach

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.


Recent research that looks at the transitioning of acute pain to chronic pain has identified neuroinflammation as a likely contributor to the process. Neuroinflammation is an inflammatory condition within nerve tissue both peripherally and centrally, in the spinal cord and brain. Inflammatory cells, called glial cells are found within the tissue matrix adjacent to and surrounding nerves. These glial cells respond to nerve injury as may occur with trauma such as surgery and normally contribute to the healing process. Cells called mast cells play a role in the activation of glial cells. However, for reasons not entirely understood, the inflammatory response of glial cells may become poorly regulated leading to pathologic inflammation around the nerve which leads to chronification of pain that persists beyond the normal healing process.


A growing body of evidence suggests that regulation of mast cells and glial cells may facilitate the healing process and at the same time reduce chronic neuroinflammation thereby reducing the development of chronic pain. Unfortunately, at this point in time much of the research is preclinical and definitive answers to the prevention and treatment of chronic pain related to neuroinflammation is still in the early phases. The good news, however, is that some agents have been identified that research indicates are safe and effective in the management of glial cell regulation and very effective for neuroinflammatory pain.


Diet and Post-Operative Pain

Diet plays multiple roles in post-operative pain. To start with the obvious, it provides nutritional support for the healing process and as such should include nutrients favorable to repairing damaged tissues. It also plays a role in inflammation including, importantly, the resolution of the acute inflammatory process that is a normal and vital part of the healing process. A significant contributing factor in the evolution of chronic pain is the failure of the acute pain and inflammation associated with a tissue injury to resolve as part of the healing process. Instead, when the inflammatory process fails to resolve, the chronification of pain ensues. Recent research has identified some of the variables in this process of inflammation resolution and the role post-operative diet may have. More comimg soon…


Palmitoylethanolamide (PEA)

Perhaps the best agent currently recommended for neuroinflammatory pain is palmitoylethanolamide (PEA), a natural substance manufactured by glial cells and also found in foods such as milk and egg yolks. PEA has good evidence to support its benefit in regulating neuroinflammation through its stabilization of mast cells and glial cells. Another safe and potentially effective natural substance that may be effective in glial cell neuroinflammation is resveratrol.

See: Palmitoylethanolamide (PEA) & Resveratrol


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.


NMDA Antagonists

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 (a potent, short-acting synthetic opioid given to patients during surgery to relieve pain and as an adjunct to an anaesthesia.)  show increased NMDA receptor activity. NMDA activity has been shown to contribute to central sensitivity and the development of chronic pain, suggesting a role for the use of NMDA antagonists for potentially reducing both immediate post-operative pain as well as for reducing the risk of the chronification of post-operative pain.


While the clinical data on the use of NMDA antagonists is growing, no definitive regimens have been defined for their use in the post-operative setting despite increasing evidence for their benefits. So far, the only studies apparently available for the use of NMDA antagonists in the peri-operative setting focus on ketamine. In principle, however, other medications with excellent safety profiles and NMDA antagonist activity are available, prescription and non-prescription.  While the NMDA activity of some 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. While studies are lacking for efficacy, generally speaking the safety of these medications is well established.

See Neurobiology of Opioids



 NMDA antagonist activity of useful medications


Choice of Opioids for Perioperative Pain


Levorphanol is an opioid with special characteristics including potent NMDA antagonism that makes it a particularly attractive choice for perioperative pain management. While appropriate for use on an as-needed basis, it offers a longer half-life compared with usual short-acting opioids including hydrocodone, oxycodone and hydromorphone.  The use of levorphanol as a suggested approach to perioperative pain management would have strong merit. While methadone also offers some degree of NMDA antagonism, the multiple complexities of methadone management likely outweigh this benefit for most patients. Tramadol (Ultram) has weak NMDA antagonist activity and may offer some benefit.

 See: Levorphanol


Adjunctive NMDA Antagonists for Paim


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. A large study published in 2015 reviewing post-operative pain in adults confirmed the benefits of both ketamine and magnesium in reducing post-operative pain intensity and improved patient satisfaction.


Intra-operative use of intravenous ketamine has been shown to reduce opiate needs in the 48-hour post-operative period in opiate-dependent patients with chronic pain. Ketamine also likely reduces opioid consumption and pain intensity throughout the post-operative period in this same patient population. This benefit has been demonstrated without significant side effects.


Post-operative use of intravenous ketamine has been shown to be effective for reducing pain in a number of clinical studies published in the last few years. While the use of ketamine intravenously is limited to in-hospital treatment by physicians, prescription topical ketamine can be prescribed and may be useful in post-op pain.

See Ketamine


Dextromethophan (DXM)

Dextromethorphan (DXM) is a common ingredient in cough and cold remedies, including Delsym, Robitussin DM and many others. Structurally, DXM is structurally related to the opioid, levorphanol, although it is not itself considered an opioid. As an NMDA antagonist, dextromethorphan when used as an adjunctive to opioids for perioperative pain may useful in reducing pain, especially neuropathic pain, as well as preventing nerve damage and hyperalgesia. While research remains conflicting and still falls short of confirming definitive benefits and doses for supplementing with DXM, there are evidence-based arguments to consider the trial use of dextromethorphan in the management of peri-operative pain.

See: Dextromethorphan (DXM)


Orphenadrine (Norflex), a medication used for muscle spasm, also has weak NMDA activity and may offer benefit in reducing  the development of hyperalgesia. When there are indications for the use of a muscle relaxer in the perioperative period, orphenadrine may offer an advantage.


Memantine (Namenda)

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.



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:



Antioxidants and Oxidative Stress

Vitamin C

NRF2 Activators

Using the Mind

Anxiety  & Stress




Preventing Pain Related to Surgery – Overviews

  1. perioperative-pain-management- 2007 pubmed-ncbi
  2. Pharmacotherapy for the prevention of chronic pain after surgery in adults (Review) – 2013
  3. optimizing-pain-management-to-facilitate-enhanced-recovery-after-surgery-pathways 2015 -pubmed-ncbi
  4. development-of-a-management-algorithm-for-post-operative-pain-mapp-after-total-knee-and-total-hip-replacement-2014
  5. Post-operative Opioid-Induced Hyperalgesia – ICM Case Summaries – 2016
  6. The Complexity Model – A Novel Approach to Improve Chronic Pain Care – 2014
  7. Postoperative_pain_from_mechanisms_to_treatment.
  8. Mechanisms of acute and chronic pain after surgery: update from findings in experimental animal models. – PubMed – NCBI – 2018
  9. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception – 2015
  10. Age and preoperative pain are major confounders for sex differences in postoperative pain outcome – A prospective database analysis – 2017
  11. Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways. – PubMed – NCBI – 2015
  12. Reward Circuitry Plasticity in Pain Perception and Modulation – 2017


Preventing Pain Related to Surgery – Neuroinflammation, Glial Cells & Mast Cells

  1. Involvement of mast cells in a mouse model of postoperative pain. – PubMed – NCBI – 2011
  2. An Inflammation-Centric View of Neurological Disease – Beyond the Neuron – 2018


Preventing Pain Related to Surgery – Resolving Inflammation

  1. Vagus nerve controls resolution and pro-resolving mediators of inflammation – 2014
  2. The Resolution Code of Acute Inflammation – Novel Pro-Resolving Lipid Mediators in Resolution – 2015
  3. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. – PubMed – NCBI – 2018
  4. Resolvins and protectins – mediating solutions to inflammation – 2009
  5. Resolvins and inflammatory pain – 2011
  6. Resolution of inflammation – an integrated view – 2013
  7. Protectins and maresins – New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome – 2014
  8. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation – 2014
  9. Novel Pro-Resolving Lipid Mediators in Inflammation Are Leads for Resolution Physiology – 2014
  10. Novel Anti-Inflammatory — Pro-Resolving Mediators and Their Receptors – 2011
  11. Lipid Mediators in the Resolution of Inflammation – 2015
  12. PPARγ activation ameliorates postoperative cognitive decline probably through suppressing hippocampal neuroinflammation in aged mice. – PubMed – NCBI – 2017
  13. Postoperative cognitive dysfunction in the aged: the collision of neuroinflammaging with perioperative neuroinflammation. – PubMed – NCBI – 2018
  14. The Role of Neuroinflammation in Postoperative Cognitive Dysfunction – Moving From Hypothesis to Treatment – 2018
  15. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms – 2017
  16. Structural Elucidation and Physiologic Functions of Specialized Pro-Resolving Mediators and Their Receptors – 2017
  17. LPS is a Switch for Inflammation in the Gut and Beyond
  18. Identification of specialized pro-resolving mediator clusters from healthy adults after intravenous low-dose endotoxin and omega-3 supplementation – a methodological validation – 2018
  19. The Protectin Family of Specialized Pro-resolving Mediators – Potent Immunoresolvents Enabling Innovative Approaches to Target Obesity and Diabetes – 2018
  20. Protectins and Maresins – New Pro-Resolving Families of Mediators in Acute Inflammation and Resolution Bioactive Metabolome – 2014
  21. Functional Metabolomics Reveals Novel Active Products in the DHA Metabolome – 2012



Preventing Pain Related to Surgery – Diet

  1. High-fat diet exacerbates postoperative pain and inflammation in a sex-dependent manner. – PubMed – NCBI 2018


Preventing Pain Related to Surgery – Genetics

  1. genotyping-test-with-clinical-factors-better-management-of-acute-postoperative-pain-2015
  2. the-impact-of-genetic-variation-on-sensitivity-to-opioid-analgesics-in-patients-with-postoperative-pain-a-systematic-review-and-meta-analysis-2015
  3. Chronic postsurgical pain – is there a possible genetic link? – 2017



Preventing Pain Related to Surgery – Epigenetics

  1. Epigenetic-regulation-of-spinal-cord-gene-expression-controls-opioid-induced-hyperalgesia-2014
  2. Epigenetic-regulation-of-opioid-induced-hyperalgesia-dependence-and-tolerance-in-mice-2013
  3. Epigenetic-regulation-of-persistent-pain-2015
  4. Chronic-opioid-use-is-associated-with-increased-dna-methylation-correlating-with-increased-clinical-pain-pubmed-ncbi
  5. Could targeting epigenetic processes relieve chronic pain states? – PubMed – NCBI
  6. Epigenetic-mechanisms-of-chronic-pain-2015
  7. Telomeres and epigenetics – Potential relevance to chronic pain – 2012
  8. Epigenetics of chronic pain after thoracic surgery. – PubMed – NCBI
  9. Epigenetics-in-the-perioperative-period-2015


Preventing Pain Related to Surgery – Gabapentin & Pregabalin

  1. Do surgical patients benefit from perioperative gabapentin:pregabalin? A systematic review of efficacy and safety. – PubMed – NCBI
  2. Perioperative administration of gabapentin 1,200 mg day−1 and pregabalin 300 mg day−1 for pain following lumbar laminectomy and discectomy – 2011
  3. Preemptive use of gabapentin in abdominal hysterectomy: a systematic review and meta-analysis. – PubMed – NCBI
  4. The Effect of Gabapentin on Acute Postoperative Pain in Patients Undergoing Total Knee Arthroplasty – 2016
  5. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. – PubMed – NCBI
  6. The use of gabapentin in the management of postoperative pain after total hip arthroplasty – 2016
  7. The use of gabapentin in the management of postoperative pain after total knee arthroplasty – 2016
  8. Use of gabapentin for perioperative pain control – A meta-analysis – 2007
  9. The efficacy of gabapentin:pregabalin in improving pain after tonsillectomy: A meta-analysis. – PubMed – NCBI
  10. Effects of gabapentin on postoperative pain, nausea and vomiting after abdominal hysterectomy: a double blind randomized clinical trial. – PubMed – NCBI
  11. Gabapentin and postoperative pain – a systematic review of randomized controlled trials 2006 – PubMed Health
  12. Preoperative Preemptive Drug Administration for Acute Postoperative Pain – A Systematic Review And Meta-Analysis – 2016
  13. the-effects-of-preoperative-oral-pregabalin-and-perioperative-intravenous-lidocaine-infusion-on-postoperative-morphine-requirement-in-patients-undergoing-laparatomy-2015
  14. perioperative-pain-management- 2007 pubmed-ncbi
  15. optimizing-pain-management-to-facilitate-enhanced-recovery-after-surgery-pathways 2015 -pubmed-ncbi
  16. Treatment_of_Neuropathic_Pain_The_Role_of_Unique_Opioid_Agents_-_2016
  17. The Anti-Allodynic Gabapentinoids – Myths, Paradoxes, and Acute Effects – 2016 
  18. Gabapentinoids as a Part of Multi-modal Drug Regime for Pain Relief following Laproscopic Cholecystectomy: A Randomized Study – 2017
  19. Effects of pregabalin and gabapentin on postoperative pain and opioid consumption after laparoscopic cholecystectomy – 2017
  20. Do surgical patients benefit from perioperative gabapentin:pregabalin? A systematic review of efficacy and safety. – PubMed – NCBI
  21. Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis. – PubMed – NCBI
  22. Effects of pregabalin and gabapentin on postoperative pain and opioid consumption after laparoscopic cholecystectomy – 2017
  23. Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort – 2018


Preventing Pain Related to Surgery – Ketamine & NMDA Antagonists

  1. Role of Ketamine in Acute Postoperative Pain Management – A Narrative Review – 2015
  2. Perioperative ketamine for acute postoperative pain. – PubMed – NCBI
  3. Ketamine decreases postoperative pain scores in patients taking opioids for chronic pain: results of a prospective, randomized, double-blind study. – PubMed – NCBI
  4. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. – PubMed – NCBI
  5. Ketamine as an Adjunct to Postoperative Pain Management in Opioid Tolerant Patients After Spinal Fusions – A Prospective Randomized Trial – 2007
  6. The efficacy of N-methyl-D-aspartate receptor antagonists on improving the postoperative pain intensity and satisfaction after remifentanil-based a… – PubMed – NCBI
  7. The clinical role of NMDA receptor antagonists for the treatment of postoperative pain. – PubMed – NCBI
  8. Ketamine – an old drug revitalized in pain medicine – 2017
  9. Effect of ketamine combined with magnesium sulfate in neuropathic pain patients (KETAPAIN) – study protocol for a randomized controlled trial – 2017


Preventing Pain Related to Surgery – Magnesium

  1. Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. – PubMed – NCBI
  2. Peri-operative intravenous administration of magnesium sulphate and postoperative pain – a meta-analysis – 2013
  3. Effect of magnesium sulfate on morphine activity retention to control pain after herniorrhaphy. – PubMed – NCBI
  4. Effect of ketamine combined with magnesium sulfate in neuropathic pain patients (KETAPAIN) – study protocol for a randomized controlled trial – 2017


Preventing Pain Related to Surgery – Nefopam

  1. nefopam-after-total-hip-arthroplasty-role-in-multimodal-analgesia-pubmed-ncbi
  2. nefopam-analgesia-and-its-role-in-multimodal-analgesia-a-review-of-preclinical-and-clinical-studies-pubmed-ncbi
  3. preventive-analgesic-efficacy-of-nefopam-in-acute-and-chronic-pain-after-breast-cancer-surgery-2016
  4. neuronal-sensitization-and-its-behavioral-correlates-in-a-rat-model-of-neuropathy-are-prevented-by-a-cyclic-analog-of-orphenadrine-pubmed-ncbi


Preventing Pain Related to Surgery – Vitamin C

Chronic Regional Pain Syndrome (CRPS)/Reflex Sympathetic Dystrophy (RSD)

  1. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture – A systematic review and meta-analysis – 2017
  2. [Vitamin C and prevention of reflex sympathetic dystrophy following surgical management of distal radius fractures]. – PubMed – NCBI
  3. Complex regional pain syndrome – recent updates – 2013
  4. Give vitamin C to avert lingering pain after fracture – 2008
  5. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures – a randomised trial – 1999
  6. Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. – PubMed – NCBI – 2009


Preventing Pain Related to Surgery – Vitamin C

Lumbar Surgery

  1. The Efficacy of Vitamin C on Postoperative Outcomes after Posterior Lumbar Interbody Fusion: A Randomized, Placebo-Controlled Trial – 2017

Emphasis on Education


Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.


For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.


Please note also, that many of the benefits for medications described on this web site include “off-label” use for a medication. Off-label prescribing refers to the use of medication for a condition not named in its FDA approval. Physicians are free to prescribe any medication they want, as long as there is some evidence for usefulness. And remember that the lack of an FDA indication does not necessarily mean lack of efficacy—it sometimes means that no drug company has deemed the investment in clinical trials worth the eventual pay off.


Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.


For more information, please contact Accurate Clinic.


Supplements recommended by Dr. Ehlenberger may be purchased commercially online or at Accurate Clinic.

Please read about our statement regarding the sale of products recommended by Dr. Ehlenberger.

Accurate Supplement Prices