Peri-operative Pain Management: 

Module 3:

POST-Operative Dietary & Nutritional Management

This section covers Module 3 of the Peri-operative Pain Protocol — POST-Operative Dietary & Nutritional Management — as part of a comprehensive approach to the management of pain associated with upcoming, planned surgical procedures. These procedures include those for the management of chronic joint, neck and back pain such as spinal fusions, artificial disc replacements, total joint replacements as well as less invasive procedures.

  • Perioperative – Before, During and After Surgery
  • Preoperative – Before Surgery
  • Postoperative – After Surgery

This guide is not intended to replace appropriate nutritional guidance that should be provided by a dietitian regarding perioperative dietary management. Please consult with your surgeon for dietary guidance including referral to a dietitian.

 

See:  

Peri-Operative Pain Management (P-OPM)

 

  

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Definitions and Terms Related to Pain

 

Module 3:

POST-Operative Dietary & Nutritional Management

Introduction – The Peri-operative Pain Management Protocol

The goal of the peri-operative pain protocol is to manage pain starting with the pre-operative period (4–6 weeks before surgery) through the post-operative period (up to 12 weeks after surgery. This protocol includes dietary & nutritional management as well as the use of nutraceuticals during both the pre-operative and post-operative periods. It is designed to reduce not only post-operative pain, but importantly, to also reduce the transitioning of post-operative pain from becoming chronic pain.

This peri-operative pain management protocol applies the principles of the 4-D chronic pain management protocols described here.The 4-D protocols engage lifestyle management as well as the use of prescription medications and therapeutic nutraceuticals based on the anti-inflammatory diet.

Strategic Framework for Protocol Development – A Modular Approach

Protocol Structure and Development Sequence

The peri-operative protocol is divided into the pre-operative period (4–6 weeks before surgery) and the post-operative period ((0–12 weeks after surgery). The pre-operative and post-operative protocols are each divided into two modules (1) Dietary & Nutritional Management and (2) Nutraceutical Management.

The four modules are presented in this order, as each builds on the prior:

   Pre-operative Management (4–6 weeks before surgery)

  • Module 1: Dietary and Nutritional Management
  • Module 2: Nutraceutical Management

   Post-operative Management (0–12 weeks after surgery)

  • Module 3: Dietary and Nutritional Management
  • Module 4: Nutraceutical Management

Outlined in the protocol are breakdowns of the responsibilities for both the surgical team and the pain management team regarding the assessment and management of the patient’s pain. Topics include pre-operative and post-operative dietary & nutritional management and recommended nutraceutical management.

Peri-operative Considerations for Patients on Chronic Opioid Management

Of note, this protocol has been established to facilitate appropriate and effective peri-operative pain management specifically directed at those pain patients who have been taking opioids chronically for their pain. Both the presence of chronic pain, as well as the long-term use of opioids, introduces significant variables that impact appropriate choices for managing the patient’s pain. An additional section is forthcoming for the management of peri-operative pain management directed at those patients with acute pain and/or non-opioid dependent pain.

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Module 3: Dietary & Nutritional Management

(0–12 Weeks Post-Operative)

OVERVIEW AND RATIONALE

This module establishes a structured post-operative dietary & nutritional management protocol following elective orthopedic surgery. The protocol spans from the immediate postoperative period through 12 weeks post-surgery, aligned with the wound healing timeline, the acute-to-chronic pain transition window, and the patient’s ~30-day clinic visit schedule.

Emphasis has been placed on support for chronic pain patients, including those on long-term opioid therapy

The rationale is grounded in three key principles:

1. Surgery triggers a catabolic stress response characterized by increased protein breakdown, insulin resistance, elevated inflammatory cytokines, and micronutrient depletion — all of which are compounded in patients with pre-existing chronic pain and chronic opioid use.[1][2][3]

2. Postoperative nutritional intake is often inadequate, particularly after hospital discharge. The ASER/POQI consensus emphasizes that post-discharge oral nutrition supplements are critical yet frequently overlooked.[1]

3. Diet directly modulates postoperative pain resolution. Preclinical evidence demonstrates that a pro-inflammatory (high-fat, standard American) diet prolongs postoperative pain and delays recovery, while dietary intervention — even initiated after surgery — can restore normal pain sensitivity and rescue chronic pain states.[4][5][6]

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SECTION 1:

POSTOPERATIVE RECOVERY PHASES AND NUTRITIONAL PRIORITIES

The 12-week postoperative period is organized into three recovery phases, each with distinct nutritional priorities aligned with wound healing biology and pain trajectory:

   Phase 1 – Acute Recovery: Days 0–14

   Inflammatory and Early Proliferative Phase

Wound healing biology: Hemostasis (hours), followed by the inflammatory phase (days 0–3) with neutrophil and macrophage infiltration, then transition to the proliferative phase (days 4–21) with fibroblast activity, angiogenesis, and early collagen deposition.[7][8]

Nutritional priorities:

    1. Immediate resumption of oral nutrition (within hours of surgery per ERAS protocols)[1][2]
    2. Protein delivery is the single most important macronutrient priority — more important than total calorie delivery[1]
    3. Target 105–140 g protein/day (for a 70 kg patient: 1.5–2.0 g protein/kg/day) during the acute catabolic phase (higher than preoperative target due to surgical stress)[9][2]
    4. Hydration: ≥64 oz/day (critical for wound healing and opioid-related constipation management)
    5. Micronutrient support for the inflammatory-to-proliferative transition (see Section 3)

Practical considerations for this population:

    1. Appetite suppression and opioid-related nausea are common in the immediate postoperative period, particularly with dose escalation for acute surgical pain
    2. Small, frequent, protein-dense meals are better tolerated than large meals
    3. Liquid protein supplements (whey protein shakes, clear protein drinks) may be necessary when solid food intake is limited
    4. Constipation management is critical — increased fiber, adequate hydration, stool softeners, and consideration of peripherally acting mu-opioid receptor antagonists (methylnaltrexone, naloxegol) if standard measures fail

—

   Phase 2 – Subacute Recovery: Weeks 2–6

   Proliferative and Early Remodeling Phase

Wound healing biology: Continued collagen deposition, wound contraction by myofibroblasts (from ~day 5), granulation tissue maturation, and transition to remodeling with type III to type I collagen replacement.[7][8][10]

Nutritional priorities:

    1. Maintain elevated protein (dietary and whey) intake: 1.2–1.5 g/kg/day[9][2]
    2. Transition from liquid supplements to whole-food protein sources as appetite recovers
    3. Anti-inflammatory dietary pattern intensification — this is the critical window for dietary modulation of the acute-to-chronic pain transition
    4. Essential amino acid (EAA) supplementation: Continue or initiate 9 g/day EAA. An RCT demonstrated that EAA supplementation (9 g/day from 1 week preop through 2 weeks postop) preserved rectus femoris muscle area (134% vs. 114% of baseline at 2 years) and quadriceps strength (159% vs. 125% at 2 years) after TKA.[11] This seperate and supplemental to whey protein supplements
    5. Vitamin C for collagen synthesis support and Complex Regional Pain Syndrome (CRPS) prevention (see Section 3)

This phase coincides with the first postoperative clinic visit (~4 weeks), providing an opportunity for dietary assessment and adjustment.

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Phase 3 – Rehabilitation and Transition Prevention: Weeks 6–12

Remodeling Phase and Chronic Pain Transition Window

  • Wound healing biology: Mature remodeling with collagen cross-linking and scar maturation (continues up to 1 year).[8][10]
  • Pain transition biology: Chronic postsurgical pain (CPSP) is defined as pain persisting beyond the expected healing period (≥2 months after most surgical procedures). The prevalence of CPSP causing substantial functional impairment is approximately 10% after all surgeries, with higher rates after certain orthopedic procedures. Preoperative pain, opioid use, and psychological factors are among the strongest predictors.[12][13]

Nutritional priorities:

    1. Transition protein intake toward long-term maintenance: 1.0–1.2 g/kg/day
    2. Full anti-inflammatory dietary pattern as the primary nutritional strategy
    3. Continued micronutrient optimization based on repeat biomarker assessment
    4. Dietary strategies to support opioid taper (if applicable) — adequate tryptophan-rich foods for serotonin synthesis, magnesium-rich foods for NMDA modulation
    5. Gut microbiome restoration — fermented foods, prebiotic fiber, diverse plant-based foods to counteract opioid-induced dysbiosis

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SECTION 2:

PROTEIN SUPPLEMENTATION STRATEGIES

   2A. Essential Amino Acid (EAA) Supplementation

EAA supplementation is the best-studied protein intervention specific to orthopedic surgery recovery:

    1. Dose: 20 g EAA twice daily between meals (total 40 g/day), starting 1 week preoperatively through 2 weeks postoperatively[14]
    2. Alternative protocol: 9 g/day from 1 week pre-op through 2 weeks post-op (lower dose, longer-term benefit demonstrated at 2 years)[11]
    3. Mechanism: EAA supplementation attenuates the p53-mediated apoptotic signaling and cytokine-cytokine receptor pathway upregulation that drives post-TKA muscle atrophy[15]
    4. Clinical outcomes: In the landmark RCT by Dreyer et al., EAA-treated patients showed -3.4% quadriceps atrophy at 2 weeks vs. -14.3% in placebo (p = 0.036), and -6.2% vs. -18.4% at 6 weeks (p = 0.001). EAA patients also performed significantly better on functional mobility tests at both timepoints.[14]

   2B. Whey Protein Supplementation

  1. Dose: 20–40 g/day, ideally as a between-meal supplement
  2. Mechanism: Whey protein increases intracellular glutathione (GSH), which neutralizes reactive oxygen species and blunts surgical stress-induced inflammation. Whey protein also provides all essential amino acids for tissue repair.[16][17][18]
  3. Particularly relevant for this population: Whey protein’s glutathione-boosting effect directly supports the 4D Protocol’s oxidative stress domain during the postoperative period when oxidative stress is maximal

   2C. HMB (β-Hydroxy-β-Methylbutyrate) Supplementation

  1. Dose: 3 g/day HMB, often combined with arginine and glutamine
  2. Evidence: HMB combined with arginine and glutamine may suppress postoperative quadriceps strength loss after TKA[19][9]
  3. Particularly relevant for sarcopenic patients or those with significant preoperative muscle wasting
  4. Protein supplementation to goal (1.2–1.9 g/kg), along with EAA augmented with HMB and resistance training, has shown benefit especially in sarcopenic patients[9]

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SECTION 3:

POST-OPERATIVE MICRONUTRIENT MANAGEMENT

   3A. Vitamin C

   Vitamin C is the single most evidence-supported micronutrient for postoperative orthopedic recovery:

  1. Dose: 500 mg–1,000 mg daily for at least 45–50 days after surgery[20][21]
  2. Complex Regional Pain Syndrome (CRPS) prevention: A propensity-matched study of 960 TKAs found that vitamin C prophylaxis (1 g daily for 40 days postoperatively) reduced CRPS incidence from 11.0% to 6.9% (OR 0.59, p = 0.024). In patients with a history of CRPS, vitamin C reduced recurrence from 71% to 19% (OR 0.09, p = 0.02).[22]
  3. A meta-analysis of three RCTs in wrist fracture patients showed a 46% risk reduction for CRPS with 500 mg vitamin C daily for 50 days.[23][21]
  4. Additional benefits: Collagen synthesis support (vitamin C is an essential cofactor for prolyl and lysyl hydroxylase), decreased inflammatory markers, and direct analgesic effects[19][7]
  5. The American Academy of Pain Medicine CRPS guidelines note that the evidence for vitamin C in CRPS prevention remains “unproven” based on a more recent large RCT showing no effect at later timepoints, though earlier meta-analyses were positive. Given the favorable safety profile and low cost, supplementation is reasonable.[20]

   3B. Vitamin D3

  1. Continue maintenance dose (2,000 IU/day) established preoperatively
  2. Orthopedic surgery itself causes acute vitamin D depletion; maintaining adequate levels supports bone healing, immune function, and muscle recovery[19]
  3. Recheck 25(OH)D at the 4-week postoperative visit; if <30 ng/mL, resume loading protocol (50,000 IU weekly × 4 weeks)

   3C. Magnesium

  1. Continue oral magnesium (glycinate or L-threonate) at preoperative dose (400–800 mg elemental Mg/day)
  2. Orthopedic surgery causes acute serum magnesium depletion — 40% of knee arthroplasty patients had low serum magnesium by postoperative day 1 (vs. 14% preoperatively)[24]
  3. Postoperative magnesium supports NMDA receptor antagonism (central sensitization prevention), vitamin D activation, and collagen stability[19][25]
  4. IV magnesium sulfate administered perioperatively by the surgical/anesthesia team reduces postoperative opioid consumption by approximately 7.4–10.5 mg morphine equivalents over 24 hours and reduces postoperative nausea, vomiting, and shivering[26][27][28]

   3D. Iron

  1. Assess for postoperative anemia, particularly after procedures with significant blood loss (spinal fusion, TJA)
  2. If ferritin <30 ng/mL or hemoglobin drops >2 g/dL from baseline, initiate iron supplementation
  3. Iron absorption is enhanced by concurrent vitamin C supplementation (already part of the protocol)

   3E. Zinc

  1. Zinc is required for DNA and protein synthesis, cell division, and immune function during wound healing[7][29][30]
  2. Dose: 15–30 mg elemental zinc/day during the acute recovery phase (Phases 1–2)
  3. Avoid doses >40 mg/day to prevent copper depletion

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SECTION 4:

BIOFLAVONOID SUPPLEMENTATION FOR POSTOPERATIVE SWELLING (TKA-SPECIFIC)

For patients undergoing total knee arthroplasty, bioflavonoid supplementation represents a high-quality, evidence-based intervention:

   Diosmin/Hesperidin (Micronized Purified Flavonoid Fraction)

  1. Dose: Diosmin 900 mg twice daily for 14 consecutive days, starting postoperative day 1[31]
  2. Evidence: A Level I multicenter RCT (330 patients, 13 centers) demonstrated that diosmin significantly reduced lower-extremity swelling at all postoperative timepoints (days 1, 2, 3, and 14) and reduced pain during motion, with no increase in complications.[31]
  3. A second RCT confirmed that diosmin/hesperidin combination increased knee flexion (78.8° vs. 53.9° on POD 1; 104.9° vs. 91° on day 14, p < 0.001) and reduced swelling at all measurement sites.[32]
  4. A systematic review of 140 studies on swelling management after TKA identified diosmin as a “promising strategy” alongside tranexamic acid, tourniquet minimization, knee flexion, and cryotherapy.[33]
  5. This intervention aligns with the 4-D Protocol’s use of quercetin and other flavonoids, though diosmin/hesperidin is a distinct compound with specific postoperative evidence

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SECTION 5:

ANTI-INFLAMMATORY DIETARY PATTERN — POSTOPERATIVE ADAPTATION

The anti-inflammatory dietary pattern initiated pre-operatively (Module 1) should be continued and intensified postoperatively, with specific adaptations for the recovery context:

   Phase 1 Adaptations: Days 0–14

  1. Prioritize easily digestible, protein-dense foods: bone broth, Greek yogurt, eggs, smoothies with whey protein
  2. Include anti-inflammatory spices in tolerable forms: turmeric in warm beverages (golden milk), ginger tea
  3. Avoid pro-inflammatory foods even when appetite is poor — processed snacks, sugary drinks, and fast food are common defaults during recovery but directly prolong postoperative pain[5][6]
  4. Omega-3-rich foods: canned salmon, sardines (convenient, no cooking required)

   Phase 2 Adaptations: Weeks 2–6

  1. Transition to full anti-inflammatory diet (Mediterranean-style) as mobility and cooking ability improve
  2. Emphasize colorful fruits and vegetables (≥5 servings/day) for polyphenol and vitamin C content
  3. Include fermented foods daily (yogurt, kefir, sauerkraut, kimchi) for gut microbiome restoration
  4. Adequate fiber (25–35 g/day) for constipation management — critical in opioid-treated patients

   Phase 3 Adaptations: Weeks 6–12

  1. Full anti-inflammatory dietary pattern as long-term maintenance
  2. Dietary Inflammatory Index (DII) reassessment if available
  3. Begin addressing any weight management goals deferred during the acute recovery period
  4. Dietary strategies to support physical rehabilitation: adequate carbohydrate intake around physical therapy sessions for energy, protein within 2 hours of exercise for muscle protein synthesis

 

Opioid-Specific Dietary Considerations Throughout:

  1. Chronic opioid use causes endocrine disruption, metabolic derangements, and gut dysbiosis that persist and may worsen with postoperative dose escalation
  2. Constipation is the most common and functionally limiting opioid side effect postoperatively — aggressive dietary management (fiber, hydration, fermented foods) should be paired with pharmacologic bowel regimens
  3. Sweet/convenient food cravings associated with chronic pain should be anticipated and addressed with prepared healthy alternatives

—

SECTION 6:

POSTOPERATIVE BIOMARKER MONITORING

Aligned with the ~30-day clinic visit schedule:

   Visit 1 ( 4 weeks postoperative):

  1. Prealbumin (responsive marker of nutritional recovery; half-life ~2 days)
  2. Serum magnesium (assess for postoperative depletion)
  3. 25(OH) Vitamin D (assess for surgical depletion)
  4. CBC with differential (assess for anemia, infection)
  5. hs-CRP (track resolution of surgical inflammatory response; compare to preoperative baseline from 4D Protocol)
  6. Dietary intake assessment: Is the patient meeting protein targets? Adhering to anti-inflammatory pattern?

   Visit 2 ( 8 weeks postoperative):

  1. Repeat hs-CRP (should be trending toward preoperative baseline; persistent elevation suggests ongoing inflammation or complication)
  2. OmegaCheck/Omega-3 Index (assess maintenance of anti-inflammatory fatty acid status)
  3. Assess for signs of acute-to-chronic pain transition: pain not improving as expected, new pain characteristics (burning, allodynia), sleep disruption, mood changes
  4. Dietary adherence reassessment

   Visit 3 ( 12 weeks postoperative):

  1. Full 4-D Protocol biomarker panel reassessment (compare to preoperative baseline)
  2. Nutritional screening tool readministration (MNA-SF)
  3. Transition to chronic pain management nutritional protocol
  4. Assess whether dietary modifications have been sustained and can be maintained long-term

—

SECTION 7:

INTEGRATION WITH THE 4D PROTOCOL DOMAINS

The post-operative dietary and nutritional interventions map to the 4-D Protocol domains as follows:

  • Systemic Inflammation  (Domain 1): Anti-inflammatory dietary pattern, omega-3-rich foods, vitamin C, protein optimization to support resolution of surgical inflammation
  • Neuroinflammation (Domain 2): Tryptophan-rich foods (turkey, eggs, dairy) for serotonin synthesis, magnesium for NMDA modulation, B-vitamin-rich foods for neurotransmitter support, fermented foods for gut-brain axis optimization
  • Oxidative Stress (Domain 3): Whey protein for glutathione synthesis, vitamin C, polyphenol-rich fruits and vegetables, zinc for SOD cofactor support
  • Mitochondrial Dysfunction (Domain 4): Adequate caloric intake to prevent mitochondrial energy deficit, magnesium and B vitamins as electron transport chain cofactors, CoQ10-rich foods (organ meats, sardines, peanuts) during the period when CoQ10 supplementation is held

References

  1. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway. Wischmeyer PE, Carli F, Evans DC, et al. Anesthesia and Analgesia. 2018;126(6):1883-1895. doi:10.1213/ANE.0000000000002743.
  2. ESPEN Guideline on Clinical Nutrition in Surgery – Update 2025. Weimann A, Bezmarevic M, Braga M, et al. Clinical Nutrition (Edinburgh, Scotland). 2025;53:222-261. doi:10.1016/j.clnu.2025.08.029.
  3. Perioperative Nutrition: Recommendations From the ESPEN Expert Group. Lobo DN, Gianotti L, Adiamah A, et al. Clinical Nutrition (Edinburgh, Scotland). 2020;39(11):3211-3227. doi:10.1016/j.clnu.2020.03.038.
  4. Effects of a Standard American Diet and an Anti-Inflammatory Diet in Male and Female Mice. Totsch SK, Meir RY, Quinn TL, et al. European Journal of Pain (London, England). 2018;22(7):1203-1213. doi:10.1002/ejp.1207.
  5. High-Fat Diet Exacerbates Postoperative Pain and Inflammation in a Sex-Dependent Manner. Song Z, Xie W, Strong JA, et al. Pain. 2018;159(9):1731-1741. doi:10.1097/j.pain.0000000000001259.
  6. Post-Operative Pain in Mice Is Prolonged by Diet-Induced Obesity and Rescued by Dietary Intervention. Guillemot-Legris O, Buisseret B, Mutemberezi V, et al. Brain, Behavior, and Immunity. 2018;74:96-105. doi:10.1016/j.bbi.2018.07.022.
  7. Nutrition in Wound Healing: Investigation of the Molecular Mechanisms, a Narrative Review. Palmieri B, Vadalà M, Laurino C. Journal of Wound Care. 2019;28(10):683-693. doi:10.12968/jowc.2019.28.10.683.
  8. Wound healing complications in gender‐affirming surgery. Weinstein B, Schechter L. Neurourology and Urodynamics. 2023;42(5):990-995. doi:10.1002/nau.25116.
  9. Nutritional Considerations in Hip and Knee Arthroplasty: A Critical Analysis of Current Evidence. Arapovic AE, Nham FH, Darwiche H, El-Othmani M. JBJS Reviews. 2024;12(8):01874474-202408000-00002. doi:10.2106/JBJS.RVW.24.00033.
  10. Assessment and Nutritional Aspects of Wound Healing. Campos AC, Groth AK, Branco AB. Current Opinion in Clinical Nutrition and Metabolic Care. 2008;11(3):281-8. doi:10.1097/MCO.0b013e3282fbd35a.
  11. Perioperative Essential Amino Acid Supplementation Facilitates Quadriceps Muscle Strength and Volume Recovery After TKA: A Double-Blinded Randomized Controlled Trial. Ueyama H, Kanemoto N, Minoda Y, Taniguchi Y, Nakamura H. The Journal of Bone and Joint Surgery. American Volume. 2023;105(5):345-353. doi:10.2106/JBJS.22.00675.
  12. Transition From Acute to Chronic Pain After Surgery. Glare P, Aubrey KR, Myles PS. Lancet (London, England). 2019;393(10180):1537-1546. doi:10.1016/S0140-6736(19)30352-6.
  13. Treatment of Acute Postoperative Pain. Wu CL, Raja SN. Lancet (London, England). 2011;377(9784):2215-25. doi:10.1016/S0140-6736(11)60245-6.
  14. Essential Amino Acid Supplementation in Patients Following Total Knee Arthroplasty. Dreyer HC, Strycker LA, Senesac HA, et al. The Journal of Clinical Investigation. 2013;123(11):4654-66. doi:10.1172/JCI70160.
  15. Essential Amino Acid Supplementation Alters the P53 Transcriptional Response and Cytokine Gene Expression Following Total Knee Arthroplasty. Muyskens JB, Winbush A, Foote DM, Turnbull DW, Dreyer HC. Journal of Applied Physiology (Bethesda, Md. : 1985). 2020;129(4):980-991. doi:10.1152/japplphysiol.00022.2020.
  16. Presurgery Exercise-Based Conditioning Interventions (Prehabilitation) in Adults Undergoing Lower Limb Surgery for Peripheral Arterial Disease. Palmer J, Pymer S, Smith GE, et al. The Cochrane Database of Systematic Reviews. 2020;9:CD013407. doi:10.1002/14651858.CD013407.pub2.
  17. Cysteine/Cystine-Rich Undenatured Whey Protein Supplement in Patients’ Pressure Ulcers Outcomes: An Open Label Study. Gutman JBL, Kongshavn PAL. Journal of Wound Care. 2019;28(Sup7):S16-S23. doi:10.12968/jowc.2019.28.Sup7.S16.
  18. Whey Protein Enhances Normal Inflammatory Responses During Cutaneous Wound Healing in Diabetic Rats. Ebaid H, Salem A, Sayed A, Metwalli A. Lipids in Health and Disease. 2011;10:235. doi:10.1186/1476-511X-10-235.
  19. Perioperative Nutritional Optimization in Total Joint Arthroplasty: From Screening to Supplementation. Siddiqi A, Yousuf KM, Chen AF, Jacob PB, Wickline A. The Journal of Arthroplasty. 2026;:S0883-5403(26)00313-X. doi:10.1016/j.arth.2026.03.088.
  20. Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition. Harden RN, McCabe CS, Goebel A, et al. Pain Medicine (Malden, Mass.). 2022;23(Suppl 1):S1-S53. doi:10.1093/pm/pnac046.
  21. Complex Regional Pain Syndrome: Advances in Epidemiology, Pathophysiology, Diagnosis, and Treatment. Ferraro MC, O’Connell NE, Sommer C, et al. The Lancet. Neurology. 2024;23(5):522-533. doi:10.1016/S1474-4422(24)00076-0.
  22. Prophylaxis Against Complex Regional Pain Syndrome Recurrence With Vitamin C in Total Knee Arthroplasty: A Propensity Score-Matched Analysis of 960 Cases. Hernigou J, Chahidi E, Everaert J, et al. The Journal of Bone and Joint Surgery. American Volume. 2025;:00004623-990000000-01567. doi:10.2106/JBJS.24.01584.
  23. Complex Regional Pain Syndrome. Goebel A. The New England Journal of Medicine. 2025;393(23):2338-2348. doi:10.1056/NEJMcp2415752.
  24. The Relation Between Acute Changes in the Systemic Inflammatory Response and Circulating Thiamine and Magnesium Concentrations After Elective Knee Arthroplasty. Maguire D, Catchpole A, Sheerins O, et al. Scientific Reports. 2021;11(1):11271. doi:10.1038/s41598-021-90591-y.
  25. Clinical Efficacy of Magnesium in Perioperative Pain Management: A Narrative Review. Ahmadzadeh S, Wentling JG, Ford BM, et al. Current Pain and Headache Reports. 2025;29(1):117. doi:10.1007/s11916-025-01422-y.
  26. Adjunctive Intravenous Magnesium Sulfate for Postoperative Pain and Opioid Reduction in Lower Extremity Orthopedic Surgery: A Double-Blind Randomized Controlled Trial. Muhammad AR, Sukmono RB, Tantri AR, Wiyarta E. Journal of Clinical Medicine. 2026;15(5):2055. doi:10.3390/jcm15052055.
  27. The Use of Intravenous Magnesium Sulfate on Postoperative Analgesia in Orthopedic Surgery: A Systematic Review of Randomized Controlled Trials. Peng YN, Sung FC, Huang ML, Lin CL, Kao CH. Medicine. 2018;97(50):e13583. doi:10.1097/MD.0000000000013583.
  28. Perioperative Systemic Magnesium to Minimize Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials. De Oliveira GS, Castro-Alves LJ, Khan JH, McCarthy RJ. Anesthesiology. 2013;119(1):178-90. doi:10.1097/ALN.0b013e318297630d.
  29. The Role of Macronutrients and Micronutrients in Wound Healing: A Narrative Review. Penny H, Flores R, Pennington E, Pedersen A, Tran S. Journal of Wound Care. 2022;31(Sup5):S14-S22. doi:10.12968/jowc.2022.31.Sup5.S14.
  30. Evidence-Based Nutritional Interventions in Wound Care. Saeg F, Orazi R, Bowers GM, Janis JE. Plastic and Reconstructive Surgery. 2021;148(1):226-238. doi:10.1097/PRS.0000000000008061.
  31. Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial. Wang Q, Jin Q, Cai L, et al. The Journal of Bone and Joint Surgery. American Volume. 2024;106(6):492-500. doi:10.2106/JBJS.23.00854.
  32. Is a Combination of Diosmin and Hesperidin Effective on Swelling, Pain, and Range of Motion After Total Knee Arthroplasty?. Girgin AB, Duman E. The Journal of Arthroplasty. 2026;41(7):2043-2050. doi:10.1016/j.arth.2025.10.058.
  33. Swelling Management in Total Knee Arthroplasty: A Systematic Review. McGarry L, Kearney J, Rotaru J, Gunaratne R. JBJS Reviews. 2025;13(9):01874474-202509000-00005. doi:e25.00109.

Emphasis on Education

 

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