“It takes but one positive thought when given a chance to survive and thrive to overpower an entire army of negative thoughts. “
– Robert H. Schuller

Acute Pain: Initial Post-Injury


Aside from concerns regarding loss or impairment of function after being injured, most people’s primary concern revolves around their pain and it’s effective management. This is especially true for patients who, prior to their acute injury, already suffer from chronic pain and belong to a population that research has shown to be hypersensitive to pain.


Management of pain in the days and weeks after an injury is important in itself. But it is also important because how well that acute pain is managed can impact the ultimate duration and severity of that pain. The goal of pain management is not “zero pain” but pain that is tolerable and allows the patient to function. What is most important to understand, however, is that the most significant, consistent factor contributing to the risk of progression of acute to chronic post-injury pain is the duration of severe acute post-injury pain which can lead to peripheral and central sensitization (explained below).


This educational section is directed at addressing these concerns and reviews what can be done in the immediate post-injury time frame to improve short term as well as long term pain outcomes.



Acute Pain – Avoiding Transition to Chronic Pain

The Transition of Acute Post-Injury Opioid Use to Chronic Opioid Use


See also:

Central Sensitization

Neurobiology of Pain

Gabapentin & Lyrica

Palmitoylethanolamide (PEA)





see also:

Considering Spine Surgery?

Coordinating Post-Operative Pain Management with the Surgeon or Dentist


Definitions and Terms Related to Pain


Key to Links:

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Red text – another page on this website

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There are four primary goals in the management of acute post-injury pain:


(1) Reduce the severity and duration of the acute post-injury pain

(2) Reduce the risk of the acute post-injury pain from becoming chronic

(3) Enhance the individual’s coping skill relative to living with pain

(4) Facilitate improved engagement in daily activities and reduce functional impairment.



Considerations in the Management of Acute Post-Injury Pain

After one suffers significant trauma resulting in injury or injuries, it is common and expected to experience pain.  How effectively that pain is initially treated is very important because poorly controlled pain after an acute injury substantially increases the risk of that pain becoming chronic, defined as pain greater than 3 months duration. Therefore, a primary consideration when treating acute pain is to assess the likelihood of the painful condition becoming chronic. When circumstances suggest an increased risk for chronification of pain, a more aggressive treatment regimen should be engaged with emphasis on a multi-modal approach (See: Avoiding Transition to Chronic Pain).


When this risk is low, a more simple, less complex treatment plan may be engaged although whenever feasible steps to reduce the chronification of pain should be included. This education section emphasizes the components of the simple, less complex treatment plan for acute post-injury pain in patients estimated to be at low risk for chronification of their pain.



Acute Post-Injury Pain Management – Overview

In addition to contributing to the chronification of pain and impairment of quality of life, poorly controlled acute post-injury pain is associated with increased complications of pain including anxiety and depression along with the use of multiple medications and their potential side effects. So, how well one addresses their acute pain after an injury may be one of the most important influences on their future quality of life.


Reearch has taught us that the preferred means of reducing post-injury pain is to engage a comprehensive, multi-modal approach. A multi-modal approach can be defined as the use of more than one therapeutic approach including different pharmacological classes of analgesic medications targeting different receptors in various pain pathways with the goal of improving analgesia while reducing individual class-related side effects. It has been said that “a good multi-modal protocol is a checklist rather than a recipe,” one that allows for flexibility in the individual components based on the patient’s comorbidities, allergies and other medications.


Post-injury pain can be nociceptive (derived from damaged tissues), neuropathic (nerve based), mixed or psychogenic, depending on the patient and the injury. As such, medications from different classes may be required for successful pain reduction while at the same time reducing reliance on opioids and limiting the evolution of chronic pain.


A comprehensive approach for treating post-injury pain is a neccesity for obtaining the best outcome, one that includes not only reduced pain and suffering but also restoration of quality and enjoyment of life and a return to functionality. Engaging a comprehensive approach requires not just the use of physical treatments performed on someone or the use of analgesics and prescription medications. It should also include lifestyle changes for long-term therapeutic effectiveness. It is important to engage in regular stretching and relaxation exercises as well as strengthening exercises for maintaining good posture.


A nutritional approach must be included to support and enhance tissue healing through eating an appropriate diet and the use of nutriceutical supplements. Finally, the psyche of an injured individual must be supported to avoid or treat the stress, anxiety and depression that commonly accompany significant injury.


This educational section reviews evidence-based information from current research directed at treating acute post-injury pain. Considerations directed at reducing the risk and/or severity of developing chronic pain after an injury is deferred to another educational section (See: Avoiding Transition to Chronic Pain). Much of the information in this section is based on studies that evaluate post-surgical pain which does differ somewhat from post-trauma pain but shares many important considerations. The study of post-surgical pain has an advantage in that these studies may allow for control subject testing, providing more accurate study conclusions.


Its important to remember that pain is a multi-dimensional emotional and sensory experience and different patients respond to pain very differently based on physiologic and psychologic factors as well as the context in which the pain is experienced. For example, perhaps the greatest difference between post-surgical and post-injury pain is that the first is usually a planned and controlled trauma while post-injury pain is neither of these. As such, post-injury pain is potentially more subject to acute physical and emotional stress related to the circumstances surrounding the injury. Since stress is a worsening influence for pain it is especially important to emphasize stress and anxiety management related to post-injury pain.


Conditions That Contribute to the Severity and Duration of Post-Injury Pain

Aside from the nature and severity of the injury itself, there are other variables that contribute to pain after an injury.


(1) The Presence of Pain Before an Acute Injury

The presence of pain priory to injury, especially chronic pain, is a factor that contributes to both acute as well as chronic post-injury pain. There is evidence that the effectiveness of management of pre-injury pain may impact the severity of acute post-injury pain.


Additionally, certain pre-existing chronic pain conditions are more likely to be associated with increased post-injury pain including chronic migraine headaches, chronic neck or low back pain, knee arthritis, fibromyalgia, chronic pancreatitis, chronic regional pain syndrome (CRPS) and other conditions. These conditions are all associated with neuropathic pain and/or peripheral sensitization and central sensitization (see below).


 (A) Neuropathic pain

Neuropathic pain, which is based on dysfunctional or dysregulated nerves, is generally experienced as burning, electric shocking or shooting in nature. A dominant component of chronic pain, neuropathic pain can also occur acutely as a component of post-injury pain.

(See: Neuropathic Pain)


(B) Central and Peripheral Sensitization

Central and peripheral sensitization are conditions associated with many common chronic pain syndromes including chronic low back pain, neck pain and whiplash syndromes, arthritis, migraine headaches, irritable bowel syndrome (IBS), inflammatory bowel conditions and many other conditions.


Sensitization of the central nervous system (brain and spinal cord) and peripheral nervous system (outside the brain and spinal cord) are common conditions that are characterized by changes in nerves including pain receptors, nerve junctions and nerve pathways in the spine and brain that occur over time with continued pain. This sensitization results in the magnification of pain experiences where what should be a mild pain is experienced as moderate or severe pain or where sensations that are  not normally painful become painful.


Patients with central and peripheral sensitization are much more likely to experience increased severity of pain after an injury, even with those injuries that are not normally considered likely to be associated with significant pain. In turn, these patients are more vulnerable for having their acute pain becoming chronic. Patients with central and peripheral sensitization can be identified and treatment should be initiated ASAP after an acute injury to reduce the  severity of their acute post-injury pain as well as reduce the likelihood and severity of transition to chronic pain.

(See: Central Sensitization)


(2) Nutritional Status

An important variable that impacts the severity of post-injury pain is the nutritional status of the patient at the time of injury and in the post-injury time period. Vitamin and other nutritional deficiencies may contribute to poor or prolonged healing and enhance pain.


Additionally, studies suggest that diet and nutrition-based supplements reduce post-injury pain by promoting healing and reducing  inflammation. While inflammation is a natural process that is important in the healing of damaged tissue, it can also lead to problems when dysregulated and prolonged. Patients with increased systemic inflammation and oxidative stress (see below) associated with certain medical conditions and unhealthy diets are more at risk for increased post-injury pain.


(3)  Oxidative Stress

“Oxidative stress” is an imbalance in the body where there are excessive “oxidants” and insufficient “antioxidants.” Oxidants are chemically active agents such as free radicals and Reactive Oxidizing Species (ROS) acquired from the diet, produced in the body or encountered in the environment. Antioxidants are chemically active agents that are also obtained from the diet or produced by the body and include CoQ-10, vitamins C and E, and curcumin. Antioxidants neutralize oxidants to help prevent the tissue damage and caused by oxidants.


Lifestyles, stress, and environmental factors that may cause excessive free radical formation and oxidative stress include:

(1) Psychological stress

(2) Air pollution.

(3) Cigarette smoke

(4) Alcohol use

(5) Toxins

(6) High blood sugar levels

(7) High intake of polyunsaturated fatty acids

(8) Radiation, including excessive sunbathing.


Oxidative stress is capable of inducing harmful changes, particularly to the central nervous system ,and has been shown to play an important role in many mechanisms involved in pain modulation and central sensitization. Elevated spinal levels of oxidants (ROS and nitric oxide) can alter pain pathways and lead to the hyperexcitability of both the peripheral and central nervous system contributing to peripheral and central sensitization and the maintenance of pain symptoms.


The overabundance of oxidants associated with oxidative stress causes damage to cells, tissue and biomolecules, (lipids, proteins and nucleic acids including RNA & DNA). In addition to enhancing pain, these damages contribute to aging and chronic diseases including chronic inflammation, arthritis, atherosclerosis, cancer, diabetes, heart diseases and stroke. Maintaining a heathy diet and lifestyle, including exercise, are the best measures one can take to reduce oxidative stress and limit the evolution of pain.

(See: Oxidative Stress)


(4) Psychological and Psychiatric States

A patient’s psychological state, both before and after an injury, is a significant factor in predicting risk for increased post-injury pain. Psychological conditions that predispose to increased post-injury pain include depression, anxiety, PTSD and pain catastrophizing. Pain “catastrophizing” is a process where patients experience their symptoms out of proportion to the nature of their condition. It is often based on underlying fears related to previous experience which can be effectively treated with education and counseling including cognitive behavior therapy. It is very important to treat these underlying conditions to limit the severity and  duration of acute post-injury pain.


Treatment to Reduce the Severity and Duration of Acute Post-Injury Pain

Medication Management


Analgesics – Non-Opioid

Over-the-counter (OTC) Analgesic Medications

Treating acute pain can be relatively straight forward. Pain medicines  (analgesics) are likely the first step to obtain immediate relief. The usual initial analgesic is an over-the-counter (OTC) medication such as acetaminophen (Tylenol) or a non-steroid anti-inflammatory drug (NSAID) such as ibuprofen (Advil) or naproxen (Naprosyn). A prescription NSAID such as meloxicam (Mobic) may be prescribed. These medications are useful for mild to moderately severe pain.


Acetaminophen (Tylenol)

Acetaminophen is perhaps the safest of the OTC analgesics with its toxicity limited to excessive dosing. Its effectiveness is generally limited to mild pain but it offers this benefit with little risk of side effects compared with the NSAIDs which are contraindicated in those with gastric ulcers and bronchial asthma, pregnant women, nursing mothers, and children amongst others.


Up until recently, the mechanism by which acetaminophen works as an analgesic was largely unknown and poorly understood. It is now known that its pain benefits comes from the actions of its metabolites, p-aminophenol, which crosses the blood-brain barrier and gets metabolized by fatty acid amide hydrolase (FAAH) to  N-acylphenolamine (AM404). AM404 acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 (CB1) receptors in the brain and spinal cord which provide analgesia. Additionally, AM404 suppresses NF-kB activation of microglia, immune cells responsible for nerve pain and central sensitization which contribute to the chronification of acute to chronic pain.


In short, while acetaminophen may provide only weak analgesic benefit directly, it may offer a long term benefit by suppressing the transition of acute to chronic pain.


It has been reported that NSAIDs may slow or impair bone healing in the setting of bone fractures or surgery. Although isolated clinical investigations have provided limited evidence to withhold NSAIDs during fracture treatment, current research does not support the need to avoid NSAIDs because of fears about bone healing. Current guidelines for managing acute pain include the use of NSAIDs for mild to moderate pain in cases of bone injury.


While NSAIDs alone may often be sufficient to provide adequate pain relief, the addition of acetaminophen (Tylenol) will enhance the benefit from NSAIDs and reduce the need for opioids. Currently there are over-the-counter products that combine these two agents in one pill.


Adjunctive Medications

As part of the multi-modal approach, adjunctive pain medications may be prescribed to supplement  primary analgesics (NSAIDs and/or opioids) to provide synergistic benefits for improving pain and to allow for reduced dosing of primary analgesic medications.  These adjunctive pain medications are also commonly used independently to reduce pain. Neuromodulators and muscle relaxers are two common classes of adjunctive medications used in acute pain management.


Neuromodular Medications
“Neuromodulator” medications are those that act directly or indirectly on nerves to reduce nerve pain such as sciatica or neuropathy. Nerve pain is generally perceived as burning, electric, tingling or sharp and is often experienced as a pain referred from one location to another. Examples of neuromodulators include gabapentin (Neurontin), pregabalin (Lyrica), topiramate (Topamax), milnacaprin (Savella), duloxetine (Cymbalta), venlafaxine (Effexor), amitryptiline (Elavil), doxepin and others. These medications are usually tolerated well, especially when initially prescribed at low doses followed by slowly increasing the dose as tolerated. Because these medications reduce pain by different mechanisms than opioids, they can be very successful in reducing pain when used synergistically with opioids.


Many of the neuromodular medications that can be used to facilitate acute pain control are also helpful in reducing anxiety, improving sleep and possibly reducing opioid analgesic tolerance and centralization of pain. The most common of these prescription medications include gabapentin (Neurontin) and pregabalin (Lyrica).

(see Gabapenten and Lyrica)


Duloxetine (Cymbalta) is a medication that was initially prescribed to manage anxiety and depression but has been found to also be effective for nerve pain. It works on pain pathways that descend from the brain down the spinal cord to inhibit pain signalling ascending up to the brain and to conscious awareness. These descending pathways are implicated in the chronification of pain as well as the sensitization process that contributes to the severity of the pain experience.

See: Duloxetine (Cymbalta)


Nutriceutical Neuromodulator Supplements

There are a number of over-the-counter (OTC) supplements that have evidence for benefit in treating nerve pain and central sensitization. The use of these supplements is safe and round out a multi-modal approach to controlling acute pain. These analgesic supplements include palmitoylethanolamide (PEA), lipoic acid, acetyl L-carnitine and cannabidiol (CBD) among others.
See: Central Sensitization


Muscle Relaxers

Medications typically prescribed for muscle tightness, spasm and spasticity such as baclofen and tizanidine (Zanaflex) can also be helpful in reducing muscle pain. Another potent muscle relaxer, orphenadrine (Norflex, Norgesic  and  Orphengesic Forte), is an anti-cholinergic drug that is an analgesic used to treat painful muscle tightness and spasms. Due to its central nervous system (CNS) and peripheral actions, orphenadrine is useful for pain of many causes, including pain from radiculopathy, muscles, and headaches.


Analgesics – Opioids

The use of opioids may prove necessary to treat severe pain when initial medications above are ineffective or not tolerated. Due to current concerns regarding the “opioid epidemic” and recent research evaluating the tendency for opioids taken for acute pain to become chronically prescribed, the use of opioids for acute pain needs to be directed carefully by the prescribing physician. It is strongly recommended that patients should use the lowest effective dose of opioids for the shortest period possible. Additionally, the use of extended release opioids are generally avoided in the acute management of pain, in part because they may have a higher rate of abuse and diversion, and because they may contribute to the chronification of opioid use.


The use of opioids for acute pain in general should be initiated with short-acting opioids such as tramadol (Ultram) or hydrocodone (Norco). Codeine, which is about 15% as potent an analgesic as hydrocodone or oral morphine, may sometimes be considered for mild to moderate pain but it is frequently not tolerated due to its common side effect of nausea. Dihydrocodeine, which is a little more potent than codeine, may also be considered but is prescribed less frequently.

See: Opioids


An important consideration in the choice of which opioid to use for acute post-injury pain is presence of nerve pain and the degree of risk the patient may have for transitioning from acute to chronic post-injury pain. Patients with nerve pain or those at high risk for transitioning may benefit from the use of opioids with secondary mechanisms of action in addition to their basic action at the mu-opioid receptor which is shared by all opioids. These opioids include those with activity on the descending pain pathways (tramadol and tapentadol) and those with NMDA antagonism (levorphanol and methadone). These secondary actions provide greater benefit for nerve pain and may reduce the transition of acute to chronic pain.

See: Transitioning from Acute to Chronic Post-Injury Pain



Tramadol (Ultram)
Tramadol is frequently the first opioid prescribed for mild to moderate pain and it has the advantage of offering potentially more benefit for nerve pain compared with many other opioids due to its secondary activity on the descending pain pathways.  It has the disadvantage of being subject to genetic variants in which a patient may be unlikely to experience analgesic benefit (7% of Caucasians, about 1% of Orientals) or may have enhanced benefit with the potential for more side effects (about 2% of people).


Hydrocodone (Norco)
Hydrocodone is commonly prescribed for acute pain and is generally well-tolerated, offering the usual side effects of opioids including sedation, nausea, altered mentation and constipation. Hydrocodone offers no secondary mechanism of action for analgesic benefit. Short acting formulations of hydrocodone also contain acetaminophen (Tylenol) which provides a synergistic benefit for pain. The presence of acetaminophen however offers the potential for liver toxicity if taken in excessive amounts (>3000 mg/day).  Oral forms of hydrocodone have an analgesic potency equivalent to oral forms of morphine where 10 mgs of hydrocodone offers the same benefit for pain as does 10 mgs of morphine.


Oxycodone (Percocet and Prolate)
Another opioid sometimes used for managing acute pain is oxycodone, commonly in formulations also containing acetaminophen (Tylenol) such as Percocet (with 325 mg acetaminophen/tablet) and Prolate (with 300 mg acetaminophen/tablet). Prolate is a newer formulation with slightly less acetaminophen that offers the advantage of providing a slightly greater buffer against accidental acetaminophen toxicity. Like hydrocodone, oxycodone offers no secondary mechanism of action for analgesic benefit.


Oxycodone is 50% more potent than hydrocodone and oral morphine and is generally reserved for moderate to severe pain. While all opioids have the potential to trigger abuse and addiction, some physicians believe oxycodone to be somewhat more prone to abuse than tramadol or hydrocodone. Additionally, oxycodone may be more likely to develop analgesic tolerance more quickly than tramadol or hydrocodone. Analgesic tolerance is when the analgesic benefit provided by oxycodone slowly weakens over time, thus requiring stronger doses to achieve the same benefit. Analgesic tolerance to oxycodone typically takes months to years to develop.

See: Opioid Tolerance



Levorphanol is an opioid with special characteristics including potent NMDA antagonism that makes it a particularly attractive choice for acute post-injury pain management, especially in those at risk for transitioning to chronic pain. 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.

 See: Levorphanol


Newer Opioids

There are two opioids that are relatively new – buprenorphine (Butrans and Belbuca) and tapentadol (Nucynta). Each of these opioids offer unique advantages over traditional opioids in the management of acute pain, including the potential for greater benefit for nerve pain and for limiting the transition of acute to chronic pain.


Buprenorphine (Butrans and Belbuca)
Buprenorphine is an opioid that is considered to be a partial opiate agonist which imparts special properties not shared by traditional opioids. It has the advantage of providing up to 12 hours of analgesic benefit per dose in the case of Belbuca, a film strip that is applied to the inside cheek. In the case of Butrans, buprenorphine is formulated as a topical skin patch that can be worn for 7 days while providing consistent analgesic benefit 24 hours/day.


Additionally, buprenorphine offers greater benefit for nerve pain and it develops tolerance very slowly compared with most traditional opioids. Most importantly, it imparts no significant respiratory depression as a side effect which makes buprenorphine the safest opioid for avoiding accidental overdose.  Buprenorphine is a preferred opioid for patients who are elderly or for those with sleep apnea or prescribed other sedating medications.


Some physicians believe that because of buprenorphine’s special properties it should be preferentially considered for early or initial use in acute pain if initial management with usual short-acting opioids is ineffective, not tolerated or less safe compared with buprenorphine.

See: Buprenorphine for Pain


Tapentadol (Nucynta)
Tapentadol is a unique opioid that offers analgesic benefit based on two mechanisms of action. First, it acts on the same mu-opioid receptor in common with all opioids to provide analgesia. Additionally, it acts on the descending pain pathways in the central nervous system that provides greater secondary benefit for nerve pain compared with traditional opioids.


Because of tapentadol’s secondary  mechanism of action, it also offers less respiratory depression than comparable analgesic doses of other opioids with the exception of buprenorphine. This makes tapentadol potentially safer to use in patients with sleep apnea and for avoiding accidental overdose.


More potent than tramadol, tapentadol has analgesic potency in a comparable range to oxycodone when prescribed at usual, typical doses. Tapentadol offers fewer side effects at equipotent doses compared with other opioids with  slower development of tolerance and it also offers less risk for abuse.

See:  Tapentadol (Nucynta)


Nutrition and Post-Injury Pain

Based on studies of post-operative pain, there are a number of nutrition-based substances, both diet-based and supplementa (nutriceuticals) that may reduce post-injury pain, acute and chronic. Because the influence of diet is largely based on the long term, the role of diet is addressed further in the section  “Avoiding the Transition of Acute to Chronic Pain.” Supplements thought to be beneficial in reducing post-injury pain will be reviewed briefly here.


Vitamin B12

See:  Vitamin B12

Vitamin B12 is necessary for the maintenance and repair of the nerve sheath (myelin) that surrounds nerves and is important in their function. It has been shown that treatment with a combination of B-vitamins (including B1, B6, B12) may improve nerve injury. Research on nerve crush injuries have shown that vitamin B12 levels are altered after nerve injury and that vitamin B12 supplementation can reduce post-traumatic degenerative structural change in nerves.  These benefits may be enhanced by the use of nonsteroidal anti-inflammatory drugs ( NSAIDs).


Furthermore, it is estimated that 5% to 40% of individuals over the age of sixty have vitamin B12 deficiency, which may further contribute to post-injury pain. Studies suggest that in addition to raising B12 levels in those with suboptimal levels, higher B12 levels may also provide a therapeutic benefit to patients with nerve injuries.

Vitamin C

See: Vitamin C

There is growing research that suggests that Vitamin C is effective in reducing post-injury pain. The mechanism of Vitamin C for reducing pain intensity is not yet fully understood. Based on a review of literature, one factor in the generation of pain, especially persistent, recurrent, or neuropathic pain, is presence of reactive oxygen species (ROS) such as superoxide and certain free radicals (See: Oxidative Stress).


These compounds can be neutralized or reduced by antioxidants, including Vitamic C which has established neuroprotective and antioxidant effects.In a recently study published in 2017, a 1-year prospective, randomized, placebo-controlled, double-blind study evaluated the impact of Vitamin C on post-operative outcomes after lumbar fusion surgery. In this study Vitamin C treatment was initiated on the first postoperative day each following morning for 45 days. Remarkably, the dosage of Vitamin C was not reported but was “chosen to be consistent with 2 previous studies of vitamin C,” which used either 500 mg or 1000 mg doses. The study concluded that Vitamin C was associated with improvement of functional status after lumbar fusion surgery, especially during the first 3 post-operative months (although it was not significantly different at 1 year after surgery).


Other studies have been published regarding the use of Vitamin C that are supportive of benefit. Research has shown that supplementation with Vitamin C significantly reduces post-operative pain and decreases morphine consumption after laparoscopic cholecystectomy (gall bladder removal). In addition, it has been shown that the concentration of Vitamin C in the blood decreases after surgery, suggesting the requirement for Vitamin C increases after trauma.Other clinical and/or experimental reports have suggested that Vitamin C leads to functional improvements of damaged nerves. These observations can be explained by a greater demand for Vitamin C caused by increased oxidative stress. Therefore there is reasonable expection of benefit (and lack of significant risk for side effects) to recommend supplementation with Vitamin C, 500 mg – 1000 mg/day, in the post-injury period to reduce the intensity of pain and improve functional outcome.

See: Oxidative Stress

Vitamin D

See: Vitamin D and Pain


Vitamin D reduces systemic inflammation, modulates cell growth, and influences the immune and neuromuscular systems.  There  is a high prevalence of vitamin D deficiency in the U.S., estimated to be 20–50% of adults. This figure may even be higher in patients with chronic pain, up to 80%.


A 2019 study of supplementation with Vitamin D in low back pain patients undergoing lumbar spinal fusion surgery suggested that it may decrease the intensity of acute postopeative pain. The authors theorized that supplementation with vitamin D may reduce systemic inflammation and recommended that LBP patients undergoing spine surgery should use vitamin D perioperatively as a supplement. The dose of Vitamin D employed in the study was 3200 IU/day but no correlation was reported regarding baseline serum levels of the patients Vitamin D.


The authors did indicate that their findings were consistent with another study demonstrating that patients with Vitamin D deficiency before spinal fusion experienced greater pain and had higher disability scores. Another study on Vitamin D blood level normalization showed decreased pain intensity and improved muscular strength in Vitamin D deficient women were achieved after 3 months of vitamin D and calcium supplementation.


For healthy adults, blood levels of 25(OH)D concentration <30 nmol/l (<12 ng/ml) indicate vitamin D deficiency, whereas 25(OH)D concentrations of 30–50 nmol/l (12–20 ng/ml) suggests insufficiency. Serum 25(OH)D concentrations above 50 nmol/l (>20 ng/ml) are considered sufficient vitamin D levels, however concentrations over >125 nmol/l (50 ng/ml) may be toxic.



See: Magnesium


Magnesium, at higher doses, has been shown to decrease opioid requirements in the perioperative setting through it mechanism of NMDA antagonism.




Physiotherapy Treatments to Reduce Acute Post-Injury Pain

The most common sources of post-injury pain are muscle, tendons and ligaments. Muscle pain arises from both the muscle  tissue itself as well as the fibrous tissue encapsulating muscle, the fascia, together referred to as myofascial pain. Myofascial pain syndrome (MPS) is the most common cause of back and neck pain, both acute post-injury pain  as well as chronic back and neck pain. Because myofascial pain is so pervasive, it is important to understand myofascial pain to provide context to understanding the various treatments recommended here.



Myofascial Pain

Myofascial pain is characterized by the presence of painful trigger points in muscles as well as muscle spasm and tightness, reduced range of motion and weakness. It can be caused by trauma or overuse of muscles and is associated frequently with cervial or lumbar spine injuries as well as extremity or joint injuries, especially shoulders.

See: Myofascial Pain


MPS starts as a localized central area of muscle contraction but evolves to include the development of myofascial trigger points (MTrP). MTrPs are taut bands of muscle that are tender to palpation but over time may evolve into sources of spontaneous pain that mo longer require triggering by palpation or movement to generate pain. Furthermore, MTrPs can develop patterns of referred pain, in which the pain can be felt distant to the MTrP itself. In fact, the referral pain patterns of some MTrPs can mimic radicular pain such as sciatica which can lead to inaccurate diagnoses and treatment. The main objective in the treatment of MPS is to resolve the spasm, reduce the pain, and inactivate the trigger points.

See: Trigger Points Therapy


Within a few weeks of developing myofascial pain, peripheral and central sensitization can develop, inducing spread of the perceived pain to larger areas than the original area of perceived pain. Furthermore, myofascial pain and MTrPs can lead to the development of peripheral and central sensitization, in which the myofascial pain becomes magnified in severity and more easily elicited with simple touch or otherwise by stimulation that would normally be considered only slightly painful.

See:Central Sensitization


Non-invasive Physiotherapy Treatments

Non-invasive treatment modalities to reduce acute post-injury pain include transcutaneous electrical stimulation, therapeutic ultrasound, manual therapy including various massage techniques and heat packs. Preferred invasive treatment methods include dry needling, local anesthetics, and botulinum injections (Botox).


Heat Therapy and Application of Hot Packs
See: Heat and Cold Therapy


The therapeutic application of heat to injured tissues with the use of hot packs or soaks is as old as time and continues to be a recommended treatment. It decreases joint stiffness and promotes muscle relaxation. Hot packs cause dilation of blood vessels in superficial tissues but may reflexly also enhance blood circulation in the deeper tissues (including improved oxygenation and nutrient delivery). This increased blood flow enhances tissue healing by delivering nutrients needed for tissue repair and removing toxins associated with the injury and repair process.


Hot packs are generally coupled with therapeutic ultrasound to provide synergistic benefit. In a 2015 study, the authors evaluated the treatment sequence of hot packs followed by therapeutic ultrasound or vice versa, therapeutic ultrasound followed by hot packs.


The results of the study revealed that the application of hot packs followed by therapeutic ultrasound provides a greater beneficial effect for pain. The authors theorized that increasing blood circulation in the trigger points with the hot packs allowed for the therapeutic ultrasound to be more effective because of increased tissue density induced by the increased blood flow.


Cryotherapy – Application of Ice and Cold Gel

See: Heat and Cold Therapy

Cryotherapy (Cold Therapy) is the application of an external cold source in order to drop tissue temperature. Cold applications include ice bags, cold gel packs, ice massage, cold water submersion, gaseous cryotherapy, and continuous-flow cryotherapy devices with and without pneumatic compression. Multiple research studies have cemonstrated significant benefit for pain control with cryotherapy after orthopedic surgery including the knee, hip, shoulder, foot and ankle, wrist and hand.


Several biologic effects occur with cold therapy. A reduction in tissue temperature results in decreased tissue swelling and less vascular permeability which reduces release of inflammatory mediators that contribute to inflammation.  Cold application causes constriction of blood vessels which reduces blood flow that results in a decrease in tissue metabolic demand and subsequent hypoxic injury. A decrease in tissue temperature increases the threshold of painful stimuli and increases tolerance to pain.


Manual Therapy

Manual therapy is often an important intervention in post-injury pain. The most common manual techniques include spinal mobilization, soft-tissue mobilization, massage, and manual traction. Manual techniques can be directed at articular structures (joint mobilization and traction) and muscle. The use of spinal manipulation (“cracking” the neck or back) has little to no benefit in the management of acute post-injury pain.


Other physical modalities can be used to reduce acute post-injury pain including transcutaneous electrical stimulation, ultrasound therapy and chiropractic manipulation.


Massage Therapy

Massage plays an important role in the treatment of pain. Massage treatment improves circulation, relieves muscle spasm, decreases pain and stress, increases relaxation, and promotes generalized relaxation and feelings of well-being that decreases perceptions of pain. Additional intervention with stretching and range of joint movement exercises increase the effectiveness of massage. Massage is thought to improve physiologic and clinical outcomes by reducing pain through physical and mental relaxation, and decrease pain through the release of endorphins.


Transcutaneous Electrical Stimulation

Systematic review studies indicate that TENS, when applied using strong, subpainful frequencies, is an effective adjunct to modulate acute orthopedic injury and postoperative pain. Transcutaneous electrical stimulation is widely used to promote analgesia and healing, reduce swelling and modify the activity of the autonomic system. TENS  modulates pain through delivery of low-voltage electric currents over the skin from a small portable device. The stimulation of large diameter peripheral afferent nerve fibers is believed to reduce pain by activating endogenous opioids and by stimulating inhibitory pain pathways. In addition, treatment with TENS promotes peripheral blood flow and facilitates the repair of nerves, tendons, ligaments and bone.


The Orthopaedic Trauma Association strongly recommends the use of TENS as an adjunctive therapy for pain relief following orthopaedic injury. The skin of the area to be treated is cleaned with soap and water to reduce electrical resistance and electrodes are placed. Electrical stimulation is typically applied to targeted areas for about 15 minutes to achieve reduced pain and swelling. Similarly, areas of dysregulated autonomic nerve activity associated with vasodilation can be treated.




Therapeutic Ultrasound Therapy

Therapeutic ultrasound is a non-invasive, painless treatment that can be engaged to promote healing and decrease pain by providing deep heating to soft tissue to improve blood flow to tendons, muscle and other tissue. It reduces muscle spasm and potentially accelerates the healing of muscle and tendon injuries. It also has a micromassage effect which enables the movement of interstitial fluid in the tissues to help reduce swelling.


Therapeutic ultrasound may have a positive effect on the inflammatory response and in the case of injured muscle, it stimulates the production of new muscle fibres rather than scar tissue.  It is used to treat conditions such as myofascial pain, trigger points, bursitis and tendonitis.


Therapeutic ultrasound for treating trigger points has been used clinically for years and is well supported by clinical experience. An early 2007 study demonstrated therapeutic ultrasound significantly reduced the short-term pain pressure sensitivity of myofascial trigger points an average 44.1% from a trigger point within the trapezius muscle after a 5-min therapeutic treatment with ultrasound. A 2018 study showed therapeutic ultrasound to be an important deep-heating treatment for myofascial pain and muscle spasms as well as for improving psychological state.


To engage therapeutic ultrasound a hand-held transducer is applied to the treatment area with a gel and moved in a circular motion over the injured or painful area with treatment sessions lasting from 5-20 minutes.


Invasive Treatment

Myofascial Trigger Point (TrP) Injections and Dry Needling

 The treatment of TrPs is typically provided in the form of either vigorous focal massage or via “dry needling,” which involves stimulation of the TrP for a few seconds with a very fine acupuncture needle but without any injected material. While the process may sound intimidating and painful, the fact is that the use of the very fine acupuncture needles is usually considered to be quite tolerable and significantly less painful than receiving a tatoo. TrPs can also be treated with a localized injection of small amounts of saline, lidocaine (an anesthetic) cortisone or botox.


For many clinicians, dry needling is the preferred method because it is less expensive and it is thought to be equally effective compared to the other techniques and it has less potential for side effects or complications. It remains controversial as to which technique is superior.


Botox for Myofascial Pain

Botulinum toxin (Botox) is a potent chemical that blocks the communication between nerves and muscles and inhibits muscle contractions in the muscles where the trigger points are located. Injecting Botox may result in pain relief when it is injected into the area. Use of Botox for the treatment of myofascial pain is still an off-label use and may be considered appropriate only for patients with a condition that does not respond to, or is judged inappropriate for, more conservative treatment.





Physical therapists prescribe many specific types of exercise with the key to successful management of post-injury pain, especiallt low back pain, is physical activity. The benefits of exercise are numerous, extending from direct  benefits to specific tissues but also to most systems in the body, including cardiovascular and digestive systems, even psychiatric conditions. Exercise is especially valuable to combat the inactivity inherent in the post-injury conditions.


Some of  the most frequently prescribed specific exercises include core stabilization involving deep spinal muscles with the main objective to enhance stiffness in the spine. Other exercises include strengthening and stretching exercises.  Stretching, exercises are often focused primarily on the lumbar spine such as the knees to chest exeercise. Aerobic exercises, especially walking, are very important.




Acute Post-Injury Pain – Overviews

  1. Preventing chronic pain following acute pain – risk factors, preventive strategies, and their efficacy – 2011
  2. Ohio Guideline for the Management of Acute Pain Outside of Emergency Departments – 2016
  3. Clinical Practice Guidelines for Pain Management in Acute Musculoskeletal Injury – 2019
  4. Medical Management of Acute Pain – 2019
  5. Pain Management Best Practices Inter-Agency Task Force Report – 2019
  6. Medical Management of Acute Pain – 2019
  7. Treatments for Acute Pain – A Systematic Review – 2020
  8. Best Practices Guidelines for Acute Pain Management in Trauma Patients – 2020
  9. chronic post-hernia repair pain-2023


Acute Post-Injury Pain – Acetaminophen (Tylenol)

  1. AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain – 2006
  2. AM404, paracetamol metabolite, prevents prostaglandin synthesis in activated microglia by inhibiting COX activity – 2017
  3. First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid – 2017
  4. Acetaminophen metabolites p-aminophenol and AM404 inhibit microglial activation 2018
  5. Pharmacological Management of Adults with Chronic Non-Cancer Pain in General Practice – 2020
  6. Analgesic Effect of Acetaminophen – A Review of Known and Novel Mechanisms of Action – 2020


Acute Post-Injury Pain – Oxidative Stress

  1. Roles of Reactive Oxygen and Nitrogen Species in Pain – 2011
  2. Clinical Relevance of Biomarkers of Oxidative Stress – 2015
  3. The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease – Potential Role of Autonomic Regulation and Epigenetic Mechanisms – 2020
  4. Neuropathic Pain – Delving into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels – 2018


Acute Post-Injury Pain – Massage

Massage for Low Back Pain – 2009


Acute Post-Injury Pain – Ultrasound Therapy

  1. Overview of Therapeutic Ultrasound Applications and Safety Considerations – 2012
  2. Randomized controlled study of the antinociceptive effect of ultrasound on trigger point sensitivity novel applications in myofascial therapy? – PubMed – 2007
  3. Effectiveness of ultrasound therapy for myofascial pain syndrome – a systematic review and meta-analysis – 2017
  4. Effect of Therapeutic Sequence of Hot Pack and Ultrasound on Physiological Response Over Trigger Point of Upper Trapezius – 2015
  5. Effectiveness of Ultrasound Therapy on Myofascial Pain Syndrome of the Upper Trapezius – Randomized, Single-Blind, Placebo-Controlled Study – 2018




Acute Post-Injury Pain – Muscle Relaxers

  1. Randomized-controlled trial of methocarbamol as a novel treatment for muscle cramps in cirrhotic patients – PubMed – 2019
  2. Randomized placebo-controlled study of baclofen in the treatment of muscle cramps in patients with liver cirrhosis – PubMed – 2016
  3. Pilot study of orphenadrine as a novel treatment for muscle cramps in patients with liver cirrhosis – 2018


Acute Post-Injury Pain – Myofascial Pain

  1. Effectiveness of Ultrasound Therapy on Myofascial Pain Syndrome of the Upper Trapezius – Randomized, Single-Blind, Placebo-Controlled Study – 2018
  2. Myofascial Pain Syndrome in the Elderly and Self-Exercise – A Single-Blind, Randomized, Controlled Trial – 2016
  3. Effect of Therapeutic Sequence of Hot Pack and Ultrasound on Physiological Response Over Trigger Point of Upper Trapezius – 2015
  4. Effectiveness of ultrasound therapy for myofascial pain syndrome – a systematic review and meta-analysis – 2017
  5. Randomized controlled study of the antinociceptive effect of ultrasound on trigger point sensitivity novel applications in myofascial therapy? – PubMed – 2007


Myofascial Pain – Muscle Cramps

  1. Association Between Long-term Quinine Exposure and All-Cause Mortality – 2017
  2. Muscle Cramps Do Not Improve With Correction of Vitamin D Insufficiency – 2019
  3. Criteria in diagnosing nocturnal leg cramps – a systematic review – 2017
  4. Treatment of nocturnal leg cramps by blockade of the medial branch of the deep peroneal nerve after lumbar spine surgery – 2015
  5. Nocturnal Cramps in Patients with Lumbar Spinal Canal Stenosis Treated Conservatively – A Prospective Study – 2014
  6. Magnesium – Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency – 2021
  7. What is the role of magnesium for skeletal muscle cramps? A Cochrane Review summary with commentary – 2021
  8. Magnesium for skeletal muscle cramps – PubMed – 2020
  9. Non‐drug therapies for lower limb muscle cramps – 2012
  10. Non-drug therapies for the secondary prevention of lower limb muscle cramps – PubMed – 2021
  11. Nocturnal leg cramps in older people – 2002
  12. Assessment – symptomatic treatment for muscle cramps (an evidence-based review) report of the therapeutics and technology assessment subcommittee of the American academy of neurology – PubMed – 2010
  13. A scoping review to identify and map the multidimensional domains of pain in adults with advanced liver disease – 2020
  14. Randomized-controlled trial of methocarbamol as a novel treatment for muscle cramps in cirrhotic patients – PubMed – 2019
  15. Randomized placebo-controlled study of baclofen in the treatment of muscle cramps in patients with liver cirrhosis – PubMed – 2016
  16. Pilot study of orphenadrine as a novel treatment for muscle cramps in patients with liver cirrhosis – 2018


Reducing Acute Post-Injury Pain – Physical Therapy

  1. Physiotherapy and Low Back Pain in the Injured Worker – An Examination of Current Practice During the Subacute Phase of Healing


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
  13. Surgically-Induced Neuropathic Pain (SNPP) – Understanding the Perioperative Process – 2013
  14. Preventing Chronic Pain following Acute Pain – Risk Factors, Preventive Strategies, and their Efficacy – 2011
  15. Regular physical activity prevents development of chronic pain and activation of central neurons – 2013
  16. Regional anaesthesia to prevent chronic pain after surgery – a Cochrane systematic review and meta-analysis – 2013
  17. Pharmacotherapy for the prevention of chronic pain after surgery in adults – 2017
  18. A systematic review of therapeutic interventions to reduce acute and chronic post-surgical pain after amputation, thoracotomy or mastectomy. – 2015
  19. Analysis of perioperative pain management in vascular surgery indicates that practice does not adhere with guidelines – a retrospective cross-sectional study – 2017
  20. Efficacy and safety of multimodal analgesic techniques for preventing chronic postsurgery pain under different surgical categories – a meta-analysis – 2017
  21. Postoperative pain—from mechanisms to treatment – 2017
  22. Local anaesthetics and regional anaesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children – 2018
  23. Chronic postsurgical pain – current evidence for prevention and management – 2018
  24. Preventive analgesia and novel strategies for the prevention of chronic post-surgical pain. – (2015)
  25. Poorly controlled postoperative pain – prevalence, consequences, and prevention – 2017
  26. Designing the ideal perioperative pain management plan starts with multimodal analgesia – 2018
  27. Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive … – PubMed – NCBI – 2017
  28. Chronic pain patient and anaesthesia – 2019
  29. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults – 2017
  30. Multimodal Analgesia, Current Concepts, and Acute Pain Considerations. – PubMed – NCBI -2017
  31. Recent Advances in Postoperative Pain Management – 2010
  32. Effect of perioperative systemic alpha2-agonists on postoperative morphine consumption and pain intensity – systematic review of randomized controlled trials- 2011
  33. Cannabinoids for Postoperative Pain – 2007
  34. Educating Patients Regarding Pain Management and Safe Opioid Use After Surgery – 2020



Preventing Pain Related to Surgery – Phantom Limb Pain

  1. Strategies for prevention of lower limb post-amputation pain: A clinical narrative review – 2018
  2. Optimized perioperative analgesia reduces chronic phantom limb pain intensity, prevalence, and frequency: a prospective, randomized, clinical trial. – PubMed – NCBI – 2011
  3. Chronic post-amputation pain – peri-operative management – Review 0- 2017


Reducing Acute Post-Injury Pain – Physical Therapy

  1. Physiotherapy and Low Back Pain in the Injured Worker – An Examination of Current Practice During the Subacute Phase of Healing


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
  3. Rescue of Noradrenergic System as a Novel Pharmacological Strategy in the Treatment of Chronic Pain – Focus on Microglia Activation – 2019


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 – Alpha-2 Agonists

  1. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of rando… – PubMed – NCBI – 2012


Preventing Pain Related to Surgery – Buprenorphine

  1. Role of buprenorphine in acute postoperative pain – 2016
  2. Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol:Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery – 2017
  3. Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion a double-blind, randomized, active-controlled trial – 2017


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
  10. A systematic review and meta-analysis of ketamine for the prevention of persistent post-surgical pain. – PubMed – NCBI – 2014
  11. Ketamine for pain – 2017
  12. Ketamine for pain management – 2018
  13. Butorphanol and Ketamine Combined in Infusion Solutions for Patient-Controlled Analgesia Administration – A Long-Term Stability Study – 2015
  14. Multimodal Analgesia, Current Concepts, and Acute Pain Considerations. – PubMed – NCBI -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 – NSAIDs


  1. Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity? – PubMed – NCBI – 2013
  2. Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of ‘sulfa’ allergy. – PubMed – NCBI 2001


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 – Tapentadol (Nucynta)

  1. Role of preemptive tapentadol in reduction of postoperative analgesic requirements after laparoscopic cholecystectomy – 2016



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


Preventing Pain Related to Surgery – Vitamin D

  1. The Preoperative Supplementation With Vitamin D Attenuated Pain Intensity and Reduced the Level of Pro-inflammatory Markers in Patients After Posterior Lumbar Interbody Fusion – 2019
  2. Vitamin D and Its Potential Interplay With Pain Signaling Pathways – 2020
  3. Vitamin D for the treatment of chronic painful conditions in adults – 2014
  4. Vitamin D in Pain Management – 2017
  5. Is there a role for vitamin D in the treatment of chronic pain? – 2017
  6. Vitamin D Deficiency and Pain – Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States- 2015


 Opioids – Transitioning from Short Term to Long Term Use

  1. How acute pain leads to chronic opioid use – 2018
  2. Characteristics of initial prescription episodes and likelihood of long-term opioid use – United States, 2006-2015
  3. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults – 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.


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