Accurate Education – Journavx (suzetrigine)

Acute Pain:

Journavx (suzetrigine)

Released in January 2025, Journavx (suzetrigine) is a new non-opioid medication for the treatment of moderate to severe acute pain,  although not yet FDA approved for chronic pain. Journavx  is the first of a new class of pain medications {Selective Nav1.8 inhibitors). This is the first new class of medicines to treat acute pain in over twenty years. 

Of note, Journavx may also be useful for acute exacerbations of chronic pain. It is hoped that this new pain medication will offer an opportunity to not only lessen the experience of acute pain but also reduce the transition from acute to chronic pain. Additionally, there is is reason to believe that it may also reduce peripheral and central sensitization, two driving forces for chronic pain.

See:

• Acute Pain – Avoiding Transition to Chronic Pain
• The Transition of Acute Post-Injury Opioid Use to Chronic Opioid Use
• Omega 3 Fatty Acids

 

See also:

• Central Sensitization
• Neurobiology of Pain
• Gabapentin & Lyrica
• Palmitoylethanolamide (PEA)
• Dextromethorphan
• Ketamine
• Levorphanol

 

see also:

• Considering Spine Surgery?
• Coordinating Post-Operative Pain Management with the Surgeon or Dentist

 

Definitions and Terms Related to Pain

 

Key to Links:

• Grey text – handout
• Red text – another page on this website
• Blue text – Journal publication

What is Journavx (suzetrigine)?

Journavx (suzetrigine) is a first-in-its-class, new medication that relieves moderate to severe pain by a mechanism that is different from how other analgesic pain medications work, including acetaminophen (Tylenol),  NSAIDs (ibuprofen, Aleve, Mobic etc.) and opioids.  It works by inhibiting pain signals generated by pain receptors, for example when triggered by acute tissue damage, from being transmitted to the central nervous system and brain so as to reduce the perception of pain. 

Since Journavx works via a unique mechanism, it can be taken along with other pain medications for added analgesic benefit. Because Journavx works on nerves in the peripheral nervous system and never enters the central nervous system or brain,  it has no potential for addiction or contribution to accidental overdose if combined with opioids.  Whether off-label use for chronic pain is effective has not been fully studied and it has not been approved for chronic pain at this time.

Although Journavx is currently FDA approved only for acute pain, is important to point out that it may actually have multiple benefits with respect to pain that as of yet have not been fully explored:

1. Possible reduction of acute pain and acute exacerbation of chronic pain
2. Possible suppression of transitioning of acute pain to becoming chronic
3. Possible suppression of Peripheral and Central Sensitization

 

1. Acute Pain and Acute Exacerbation of Chronic Pain

Acute pain is the first response to damaged tissue, followed by inflammation that triggers swelling of the area and promotes tissue repair.  However, if the pain persists for more than 3 months, it is defined as chronic and it becomes a pathological condition in itself.  This temporal parameter is used to define the distinction between acute and chronic pain because there are no biomarkers or measurable physiological conditions that distinguish acute from chronic pain.

Acute pain is most commonly experienced after surgery and after significant trauma. Therefore, Journavx should be considered as a potential treatment option for these pain conditions. It has been noted, however, that although Journavx has not yet been approved for acute exacerbation of chronic pain it could be considered under those circumstances as well. As a newly approved medication, there is a limited number of clinical studies demonstrating its benefits for pain.

Early Clinical Experience with Journavx for acute pain – The following studies have assessed Journavx treatment of a variety of acute pains:

(1) Acute surgical and 34 nonsurgical pain – A study of 222 surgical and 34 nonsurgical participants aged 18 to 80 who were experiencing moderate to severe acute pain from a broad range of surgical and non-surgical causes. Surgical cases were predominantly orthopedic (41.9%), plastic (37.4%), and ENT (10.8%), while nonsurgical cases included sprains and strains. Participants received suzetrigine (100 mg loading dose, then 50 mg every 12 hours), for up to 14 days or until their pain resolved.

At the end of treatment, 83.2% of participants rated suzetrigine as good, very good, or excellent for pain relief based on the patient global assessment. Suzetrigine was generally safe; most Side effects were mild to moderate – most commonly headache, occurring in 7% of patients.

(2) Ttummy tuck and bunionectomy – Two phase 2 clinical trials of Journavx have’been conducted involving participants with acute pain after abdominoplasty (tummy tuck) or bunionectomy. As compared to placebo, Journavx was found to be effective over 48 hours for the acute pain associated with these conditions. Reported side effects were only mild to moderate in severity but included headache, nausea, diarrhea or constipation,  dizziness, and muscle spasms . (ClinicalTrials.gov numbers, NCT04977336 and NCT05034952).

 

Proposed benefits for acute exacerbations of chronic pain

(1) Acute Exacerbation of Chronic Osteoarthritis Pain – Osteoarthritis (OA) is a currently incurable, chronic, progressive, and debilitating musculoskeletal condition. One of its hallmark symptoms is chronic nociceptive (pain derived from tissue damage) and neuropathic (nerve) pain, which significantly reduces the quality of life of patients with OA. Although research into the mechanisms of OA pain is ongoing and several pain pathways are well understood, the true source of OA pain remains unclear. Voltage-gated sodium ion channels are key mediators of OA pain and are involved in all major synovial joint tissues in the context of pain generation. As such, this new class of medication may have the potential to target pain in patients with OA.

(2) Acute Exacerbation of Chronic Rotator Cuff Pain Chronic pain in biceps tendinopathy, characterized by pain and weakness in the tendon of the long head of biceps brachii muscle, is presumed to arise from neurogenic inflammation, central pain sensitization, excitatory nerve augmentation, inhibitory nerve loss, and/or dysregulation of supraspinal structures.  Multiple ion channels are involved in these pain pathways including TRPV1 and 3, TRPA1, TRPM8, Nav1.7, Nav1.8, and Nav1.9, suggesting potential benefit of suzetrigine for acute rotator cuff injury. 

2. Possible suppression of transitioning of acute pain to becoming chronic

To understand how Journavx may possibly contribute to the suppression of peripheral and sensitization, it is necessary to understand some of the details of how Journavx works.

How Journavx Works: NaV1.8 Sodium Channels and Pain Signaling

The experience of pain originates when pain receptors (nociceptors) at the site of injury are triggered and these receptors send signals along peripheral nerves in the form the form of action potentials. These action potentials propagate signals through the nerves in the peripheral nervous system (PNS), where they then enter the spinal cord and into the central nervous system (CNS). In the dorsal horn of the spinal cord these pain signals are then propagated to several brain regions resulting in the perception of pain.

The propagation of nerve signals is driven by voltage-gated sodium channels, or “NaV“s. In nerves, sodium channels are specialized membrane proteins that allow sodium ions to pass through the cell membrane. Sodium channels are primarily voltage-gated channels, meaning they open or close in response to changes in the electrical potential (voltage) across the cell membrane. These channels are crucial for generating and propagating action potentials, the electrical signals that allow nerve cells to communicate. They are found in excitable cells like neurons, muscle cells, and endocrine cells.

Following pain receptor stimulation, these sodium channels in pain-sensing nerves open, allowing an influx of sodium ions which generates action potentials (nerve impulses) that are transmitted to the brain. There are nine NaV subtypes distributed throughout the body and some of them are predominantly found in the CNS, while others are found in the heart or muscle.

Three NaV subtypes that are related to pain and are predominantly found in peripheral pain nerves are:

1. 1. NaV1.7 which are associated with certain neuropathies. Congenital absence of this channel manifests as lack of pain perception
   2. NaV1.8 which are associated with the transmission of nerve impulses from damaged or inflamed tissues and plays a crucial role in transmitting pain signals in the peripheral nervous system. It is found primarily in small-diameter sensory neurons in the dorsal root ganglion and trigeminal ganglion, which are involved in pain perception.
   3. NaV1.9 which are been associated with episodic pain syndromes.

After nerve injury or inflammation, Nav1.8 expression (population) increases in sensory nerves, further exacerbating neuronal hyperactivity and pain.Nav1.8 is responsible for the majority of sodium current during the upstroke of action potentials in nociceptors. Its fast recovery from inactivation allows sustained firing, which drives hyperexcitability and sensitization.

Journavx is highly selective for the inhibition of NaV1.8 relative to other NaV channels. NaV1.8 is a sodium channel that is mostly found in peripheral pain-sensing nerves (nociceptors), whose role is to transmit pain signals (action potentials) along peripheral nerve pathways, transmitting pain signals from the periphery to the spinal cord where the signals are then transmitted to the brain. By inhibiting the NAV 1.8 sodium channel. the transmission of pain signals is reduced by Journavx.

Other available sodium channel blockers are non-specific, meaning they block all sodium channels. For example, Novocain, lidocain or Bupivacaine, are non-specific and block all sodium channels on nerve cells. However, nonspecific sodium channel blockers have a major problem: they affect sodium channels in the brain which can cause loss of balance, double vision, sleepiness, and confusion.

Unlike non-specific sodium channel blockers (e.g., lidocaine),  Journavx is is highly selective for Nav1.8 only, peripherally acting only and does not impact the brain. As a result, Journavx avoids CNS side effects such as sedation, respiratory depression and abuse or addiction risk. Who she

 

How Journavx may suppress the development of peripheral and central sensitization

Research continues in an effort to understand how NaV1.8 inhibitors such as Journavx may reduce the hypersensitivity to pain associated with the development of peripheral and central sensitization, including inflammatory and neuropathic (nerve) pain.

Peripheral vs Central Sensitization

Symptoms of peripheral sensitization can overlap with those of central sensitization. One difference between peripheral and central sensitization can be identified easily: peripheral sensitization becomes heat-sensitive whereas central sensitization does not.

Peripheral sensitization can be characterized by:

• • Increased responsiveness and lowered firing thresholds of peripheral pain receptors
  • activation of silent pain receptors (nociceptors) that increases the nociceptive receptor field

Primary hyperaglesia:

• • Associated redress and swelling
  • Heat hyperalgesia
  • Pain may be responsive to NSAIDs

Signs that indicate peripheral sensitization is likely:

• • Distribution of symptoms is within a discreet area of tissue damage
  • Hyperalgesia at or close to the site of tissue damage
  • Pain described as burning or deep and achy
  • Pain worsens with heat
  • Pain often present at night

Central sensitization can be characterized by:

Sensitization occurs at the spinal cord level, resulting in increased receptor field size and increased responsiveness/lowered threshold to noxious and non-noxious stimuli

Secondary hyperalgesia:

• • Allodynia
  • Diffuse, widespread pain (non-dermatomal)
  • Temporal summation
  • Pain is more responsive to anti-epileptic (gabapentin, Lyrica) or anti-depressant (Cymbalta) medications

  

References:

Suzetrigine

1. Vertex Announces FDA Acceptance of New Drug Application for Suzetrigine for the Treatment of Moderate-to-Severe Acute Pain – 2024
2. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain – PubMed – 2023
3. Sodium Channels in Pain – 2024
4. www.sodiumchannels.com
5. Nav1.7 and Nav1.8- Role in the pathophysiology of pain – 2019
6. A Phase 3, Single-Arm Study of Suzetrigine, a Non-Opioid, Pain Signal Inhibitor For Treatment of Acute Pain From Surgical and Non-surgical Conditions 2024

 

Regulation of pain & ion channels

1. Peripheral mechanisms of peripheral neuropathic pain – 2023
2. Communicating pain – emerging axonal signaling in peripheral neuropathic pain – 2024
3. Pain Management Strategies in Osteoarthritis – 2024
4. Regulation of pain neurotransmitters and chondrocytes metabolism mediated by voltage-gated ion channels- A narrative review – 2023
5. Ion channels involved in inflammation and pain in osteoarthritis and related musculoskeletal disorders – 2023
6. Ion channels in osteoarthritis_ emerging roles and potential targets – PubMed – 2024

 

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
22. Anti-Inflammatory and Pro-Resolving Lipid Mediators – 2009

 

   

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

See: 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.

 

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.

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