Acute Pain: 

Preventing Acute Pain from Developing into Chronic Pain

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Definitions and Terms Related to Pain

 

Preventing Acute Pain from Developing into Chronic Pain

When managing acute pain, it is important to understand peripheral and central sensitization and their role in reducing the transition from acute to chronic pain.

Peripheral Sensitization

See: Central Sensitization

  Definition

Peripheral sensitization is the increased responsiveness and reduced activation threshold of peripheral nociceptors due to inflammatory, chemical, or tissue injury stimuli, resulting in heightened pain perception localized to the affected area.

  Role in Acute-to-Chronic Pain Transition

Peripheral sensitization drives the transition from acute to chronic pain by sustaining nociceptor hyperactivity, which, if unresolved, amplifies pain signaling and triggers central nervous system changes, including central sensitization (Woolf, 2010). Persistent peripheral input from inflammation or injury (e.g., postoperative or traumatic pain) can lead to chronic pain states like chronic postsurgical pain (CPSP) or complex regional pain syndrome (CRPS) (Parisien et al., 2022). Early intervention to reduce nociceptor excitability, such as with selective NaV1.8 inhibitors like suzetrigine, is critical to prevent this progression. See: Acute-to-Chronic Pain Transition

  Symptoms and Signs Peripheral Sensitization

  • Localized Pain: Intense, burning, or throbbing pain at the injury site.
  • Hyperalgesia: Exaggerated pain response to noxious stimuli in the affected area.
  • Allodynia: Pain from non-noxious stimuli (e.g., light touch) at the injury site.
  • Erythema and Swelling: Local inflammation with warmth or edema.
  • Spontaneous Pain: Ongoing burning or stinging pain without stimuli.

  Mechanisms of Development of Peripheral Sensitization

1.  Inflammatory Mediators: Prostaglandins, bradykinin, histamine, and cytokines (e.g., IL-1β, TNF-α) lower nociceptor thresholds via activation of receptors (e.g., TRPV1, ASIC), perpetuating pain signaling (Woolf, 2010).

2.  Ion Channel Modulation: Upregulation of sodium channels (e.g., NaV1.7, NaV1.8) and TRPV1 on nociceptors increases excitability, sustaining pain (Basbaum et al., 2009).

3.  Neurotransmitter Release: Substance P and CGRP amplify local inflammation, further sensitizing nociceptors (Ji et al., 2018).

4.  Nerve Growth Factor (NGF): NGF activates TrkA receptors, promoting channel expression and synaptic signaling, which can persist if inflammation is unresolved (Woolf, 2010).

Therapeutic Measures to Reduce Peripheral Sensitization and Prevent Chronic Pain

The following treatments target peripheral sensitization to reduce acute pain intensity and prevent sustained nociceptive input from triggering central sensitization and chronic pain. Suzetrigine is included as a novel option due to its selective NaV1.8 inhibition, which directly addresses nociceptor excitability.

1.  Traditional Prescription Medications:

  • Suzetrigine (Journavx):
    1. Mechanism: A highly selective oral NaV1.8 inhibitor that binds to the second voltage-sensing domain (VSD2) of NaV1.8 channels on peripheral nociceptors, stabilizing the closed state and reducing pain signal transmission (action potentials) in dorsal root ganglion (DRG) neurons (Hu et al., 2025). NaV1.8 is expressed exclusively in peripheral pain-sensing neurons, avoiding CNS side effects or addictive potential (Lechner et al., 2025).
    2. Role in Chronic Pain Prevention: By selectively inhibiting NaV1.8, suzetrigine reduces peripheral nociceptor hyperactivity in acute pain settings (e.g., postoperative, traumatic), decreasing the risk of central sensitization. Its efficacy in reducing pain intensity within 48 hours post-surgery (e.g., abdominoplasty, bunionectomy) suggests it can interrupt the peripheral-to-central pain amplification that drives chronicity, offering a non-opioid alternative to reduce reliance on addictive analgesics (Jones et al., 2023; Corrigan-Curay, 2025).
    3. Protocol: Oral loading dose of 100 mg, followed by 50 mg every 12 hours for up to 14 days or until pain resolves, starting within 24–48 hours post-injury or surgery.
    4. Evidence: Phase 3 trials (NAVIGATE 1 and 2) demonstrated significant pain reduction (SPID48: 48.4 points for abdominoplasty, 36.8 points for bunionectomy vs. placebo; P < .001) with a favorable safety profile (no serious AEs related to suzetrigine). Efficacy was comparable to hydrocodone/acetaminophen, with fewer discontinuations (9.2% vs. 27.6% for abdominoplasty) (Jones et al., 2023). A single-arm phase 3 study showed 83.2% of patients with surgical/nonsurgical acute pain rated suzetrigine as good to excellent (Lechner et al., 2025).
    5. Considerations: Common side effects include itching, muscle spasms, elevated creatine phosphokinase, and rash. Contraindicated with strong CYP3A inhibitors; avoid grapefruit. May temporarily reduce female fertility during treatment.
    6. Cost ($15.50 per 50 mg pill) may limit access compared to generic opioids (NCThirdAge, 2025)

 

    1. Mechanism: Bind to α2δ subunit of calcium channels, reducing neurotransmitter release (e.g., substance P, glutamate) from sensitized nociceptors.
    2. Role in Chronic Pain Prevention: Decreases peripheral input to prevent central sensitization, particularly in postoperative and neuropathic pain.
    3. Protocol:
      1. Gabapentin 300–600 mg 3x/day,, titrated to 1800–3600 mg/day; P
      2. Pregabalin 75–150 mg 2x/day, for 2–4 weeks.
    1. Evidence: Reduces postoperative pain and CPSP risk (Chou et al., 2016).
    2. Considerations: Monitor for sedation, dizziness; taper to avoid withdrawal

 

  • NSAIDs (e.g., Ibuprofen, Celecoxib):
    1. Mechanism: Inhibit COX enzymes, reducing prostaglandin-mediated nociceptor sensitization.
    2. Role in Chronic Pain Prevention: Short-term use controls acute inflammation, reducing chronicity risk; prolonged use may impair resolution (Parisien et al., 2022).
    3. Protocol: Ibuprofen 400 mg 3x/day, or celecoxib 100 mg 2x/day, for 3–7 days.
    4. Evidence: Effective in acute musculoskeletal and postoperative pain (Serhan et al., 2008).
    5. Considerations: Limit duration; avoid in renal or GI disease.

2. Topical Medications

  • Lidocaine:
    1. Mechanism: Lidocaine blocks sodium channels
    2. Role in Chronic Pain Prevention: Reduces localized nociceptor activity, minimizing central amplification (Derry et al., 2014).
    3. Protocol: Lidocaine 5% patch 12 hours/day;
    4. Evidence: Effective for localized neuropathic pain (Derry et al., 2014).
    5. Considerations: Inconsistent coverage by insurance
  • Capsaicin:
    1. Mechanism: Capsaicin desensitizes TRPV1 receptors.
    2. Role in Chronic Pain Prevention: Reduces localized nociceptor activity, minimizing central amplification (Derry et al., 2014).
    3. Protocol: Capsaicin 0.025–0.075% cream TID.
    4. Evidence: Effective for localized neuropathic pain (Derry et al., 2014).
    5. Considerations: Capsaicin may cause initial burning.

3.  Complementary Alternative Treatments:

    1. Mechanism: Modulates nociceptor activity via opioid release and autonomic regulation.
    2. Role in Chronic Pain Prevention: Reduces peripheral pain signaling, lowering central sensitization risk (Vickers et al., 2018).
    3. Protocol: 1–2 sessions/week for 4–6 weeks.
    4. Evidence: Effective in acute musculoskeletal pain (Vickers et al., 2018).
    5. Considerations: Requires trained practitioners.
    6. See: Acupuncture- Transition of Acute to Chronic Pain:
    1. Mechanism: Reduces inflammation and nerve conduction, decreasing nociceptor excitability.
    2. Role in Chronic Pain Prevention: Controls acute inflammation, preventing prolonged sensitization (Bleakley et al., 2012).
    3. Protocol: Cold packs 10–20 min every 2 hours for 48 hours.
    4. Evidence: Effective in acute trauma (Bleakley et al., 2012).
    5. Considerations: Avoid prolonged use.

•  Transcutaneous Electrical Nerve Stimulation (TENS):

    1. Mechanism: Inhibits nociceptive input via gate control theory.
    2. Role in Chronic Pain Prevention: Reduces peripheral input, preventing central changes (Johnson et al., 2015).
    3. Protocol: 30–60 min daily for 2–4 weeks.
    4. Evidence: Moderate evidence for acute pain (Johnson et al., 2015).
    5. Considerations: Variable efficacy.

4.  Nutrient-Based Treatments:

    1. Mechanism: Promote resolvins, reducing inflammatory mediators.
    2. Role in Chronic Pain Prevention: Facilitates inflammation resolution, preventing chronicity (Calder, 2017).
    3. Protocol: 1–3 g/day for 8–12 weeks.
    4. Evidence: Reduces inflammatory pain in postoperative models (Calder, 2017).
    5. Considerations: Monitor for bleeding risk.

•  Curcumin:

    1. Mechanism: Inhibits NF-κB and COX-2, reducing sensitization.
    2. Role in Chronic Pain Prevention: Controls inflammation, reducing central sensitization risk (Daily et al., 2016).
    3. Protocol: 500–1000 mg/day for 4–8 weeks.
    4. Evidence: Effective in postoperative pain (Daily et al., 2016).
    5. Considerations: Use bioavailable formulations.

•  Palmitoylethanolamide (PEA):

    1. Mechanism: Modulates mast cells, reducing inflammation.
    2. Role in Chronic Pain Prevention: Decreases nociceptor excitability, preventing chronic pain (Paladini et al., 2016).
    3. Protocol: 600 mg 2x/day, for 4–8 weeks.
    4. Evidence: Reduces postoperative pain (Paladini et al., 2016).
    5. Considerations: Limited availability

References:

  1. Woolf, C. J. (2010). Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 152(3 Suppl), S2–S15.
  2. Basbaum, A. I., et al. (2009). Cellular and molecular mechanisms of pain. Cell, 139(2), 267–284.
  3. Ji, R. R., et al. (2018). Pain regulation by non-neuronal cells and inflammation. Science, 354(6312), 572–577.
  4. Parisien, M., et al. (2022). Acute inflammatory response via neutrophil activation. Science Translational Medicine, 14(644), eabj9954.
  5. Serhan, C. N., et al. (2008). Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators. Nature Reviews Immunology, 8(5), 349–361.
  6. Chou, R., et al. (2016). Management of postoperative pain. The Journal of Pain, 17(2), 131–157.
  7. Derry, S., et al. (2014). Topical lidocaine for neuropathic pain in adults. Cochrane Database of Systematic Reviews, (7), CD010958.
  8. Vickers, A. J., et al. (2018). Acupuncture for chronic pain. The Journal of Pain, 19(5), 455–474.
  9. Bleakley, C. M., et al. (2012). Cold-water immersion for muscle soreness. Cochrane Database of Systematic Reviews, (2), CD008262.
  10. Johnson, M. I., et al. (2015). Transcutaneous electrical nerve stimulation for acute pain. Cochrane Database of Systematic Reviews, (6), CD006142.
  11. Calder, P. C. (2017). Omega-3 fatty acids and inflammatory processes. Biochemical Society Transactions, 45(5), 1105–1115.
  12. Daily, J. W., et al. (2016). Efficacy of turmeric extracts. Journal of Medicinal Food, 19(8), 717–729.
  13. Paladini, A., et al. (2016). Palmitoylethanolamide in chronic pain. Pain Physician, 19(2), 11–24.
  14. Hu, S., et al. (2025). Suzetrigine: The first NaV1.8 inhibitor approved for moderate to severe acute pain. Drug Discovery and Therapeutics, 19(1), 80–82.
  15. Lechner, S. M., et al. (2025). Suzetrigine, a non-opioid NaV1.8 inhibitor with broad applicability for moderate-to-severe acute pain. Pain and Therapy.
  16. Jones, J., et al. (2023). Selective inhibition of NaV1.8 with VX-548 for acute pain. New England Journal of Medicine, 389(5), 393–405.
  17. Corrigan-Curay, J. (2025). FDA approves suzetrigine for treatment of acute pain. Drug Topics.
  18. NCThirdAge. (2025). Post on X regarding suzetrigine cost.

Central Sensitization

  Definition

Central sensitization is a heightened state of excitability in the central nervous system (spinal cord and brain), where dorsal horn neurons or higher pain-processing centers amplify pain signals, leading to widespread pain perception and reduced pain thresholds beyond the initial injury site.

  Role in Acute-to-Chronic Pain Transition

Central sensitization is a key mechanism in chronic pain development, transforming acute pain into a persistent, amplified state that outlasts tissue healing. Prolonged peripheral input from peripheral sensitization or intense acute pain (e.g., surgery, trauma) triggers synaptic plasticity and glial activation in the CNS, leading to maladaptive changes that sustain pain independently of peripheral stimuli (Woolf, 2010). This is evident in fibromyalgia, CPSP, and CRPS. Suzetrigine’s role in reducing peripheral nociceptive input may indirectly mitigate central sensitization by decreasing the peripheral drive that initiates CNS amplification, particularly in acute pain settings (Lechner et al., 2025).

See: Acute-to-Chronic Pain Transition

  Symptoms and Signs

  • Widespread Pain: Diffuse or bilateral pain beyond the injury site.
  • Hyperalgesia: Exaggerated pain response across multiple regions.
  • Allodynia: Pain from non-noxious stimuli in a wider area.
  • Sensory Amplification: Increased sensitivity to light, sound, or temperature.
  • Fatigue and Mood Changes: Associated with CNS dysfunction, often with anxiety or depression.
  • Quantitative Sensory Testing (QST) Findings: Reduced pain thresholds, temporal summation, or impaired conditioned pain modulation.

Therapeutic Measures to Reduce Central Sensitization and Prevent Chronic Pain

The following treatments target central sensitization to reduce amplified pain signaling and prevent chronic pain. Suzetrigine is included due to its potential to indirectly reduce central sensitization by decreasing peripheral nociceptive input, though its primary action is peripheral.

1.  Traditional Prescription Medications:

    1. Mechanism: Selectively inhibits NaV1.8 channels in peripheral nociceptors, reducing pain signal transmission to the CNS. By decreasing peripheral input, suzetrigine may prevent the initiation or maintenance of central sensitization driven by sustained nociceptive barrage (Lechner et al., 2025).
    2. Role in Chronic Pain Prevention: Suzetrigine’s ability to reduce acute pain intensity within 48 hours (e.g., SPID48 reductions in phase 3 trials) limits peripheral drive to the CNS, potentially preventing synaptic plasticity and glial activation that lead to chronic pain. Its non-opioid nature reduces reliance on addictive analgesics, which can exacerbate central sensitization via opioid-induced hyperalgesia. However, its direct effect on established central sensitization is limited, as NaV1.8 is not expressed in the CNS (Hu et al., 2025; Waxman, 2025).
    3. Protocol: Oral loading dose of 100 mg, followed by 50 mg every 12 hours for up to 14 days, starting within 24–48 hours post-injury or surgery.
    4. Evidence: Phase 3 trials showed significant pain reduction in postoperative pain (abdominoplasty: 48.4% SPID48 vs. placebo; bunionectomy: 36.8%; P < .001), comparable to hydrocodone/acetaminophen, with 83.2% of patients in a single-arm study reporting good to excellent outcomes (Jones et al., 2023; Lechner et al., 2025). Phase 2 data in diabetic peripheral neuropathy suggest some efficacy in neuropathic pain, but a phase 2 trial in lumbosacral radiculopathy (sciatica) showed no benefit over placebo, indicating limited efficacy for chronic pain with central components (Dolgin, 2025).
    5. Considerations: Side effects include itching, muscle spasms, elevated creatine phosphokinase, and rash. Contraindicated with strong CYP3A inhibitors; avoid grapefruit. Cost ($15.50 per pill) and lack of CNS activity may limit its role in chronic pain with central sensitization. Ongoing phase 3 trials in diabetic peripheral neuropathy may clarify its neuropathic pain role (Vertex, 2025).
    1. Mechanism: Reduce dorsal horn excitability by inhibiting glutamate release.
    2. Role in Chronic Pain Prevention: Prevents synaptic plasticity and glial activation, reducing chronic pain risk (Chou et al., 2016).
    3. Protocol:
      • Gabapentin 300–600 mg 3x/day, titrated to 1800–3600 mg/day;
      • Pregabalin (Lyrica) 75–150 mg 2x/day, for 4–12 weeks.
    4. Evidence: Effective in fibromyalgia and postoperative pain (Chou et al., 2016).
    5. Considerations: Monitor for sedation; taper slowly.

•  Low-Dose Naltrexone (LDN):

    1. Mechanism: Inhibits microglial activation, reducing neuroinflammation.
    2. Role in Chronic Pain Prevention: Prevents glial-driven chronic pain (Younger et al., 2014).
    3. Protocol: 1–2 mg nightly, titrated to 3–4.5 mg for 4–12 weeks.
    4. Evidence: Reduces pain in fibromyalgia and CRPS (Younger et al., 2014).
    5. Considerations: Off-label; avoid in opioid-dependent patients.

:•  Ketamine

    1. Mechanism: NMDA receptor antagonist, reducing synaptic plasticity.
    2. Role in Chronic Pain Prevention: Prevents chronic pain in high-risk settings (Cohen et al., 2018).
    3. Protocol: Low-dose IV (0.1–0.5 mg/kg over 40 min) for 1–3 sessions.
    4. Evidence: Effective in acute trauma and CPSP prevention (Cohen et al., 2018).
    5. Considerations: Requires specialized setting.

•  Cymbalta (Duloxetine) or Amitriptyline:

    1. Mechanism: Enhance descending inhibition via serotonin/norepinephrine reuptake.
    2. Role in Chronic Pain Prevention: Restores pain modulation, preventing chronicity (Finnerup et al., 2015).
    3. Protocol: Duloxetine 30–60 mg/day; amitriptyline 10–25 mg nightly for 4–12 weeks.
    4. Evidence: Effective in fibromyalgia and neuropathic pain (Finnerup et al., 2015).
    5. Considerations: Monitor for side effects.

2.  Complementary Alternative Treatments:

•  Cognitive Behavioral Therapy (CBT):

    1. Mechanism: Reduces pain catastrophizing, modulating descending pathways.
    2. Role in Chronic Pain Prevention: Addresses psychosocial drivers, preventing central sensitization (Ehde et al., 2014).
    3. Protocol: 4–8 sessions over 4–12 weeks.
    4. Evidence: Reduces chronic pain risk in acute settings (Ehde et al., 2014).
    5. Considerations: Requires trained therapists.

•  Mindfulness-Based Interventions:

    1. Mechanism: Decreases stress-induced pain amplification.
    2. Role in Chronic Pain Prevention: Mitigates neuroinflammatory triggers (Hilton et al., 2017).
    3. Protocol: Meditation or yoga 10–20 min/day for 4–8 weeks.
    4. Evidence: Reduces pain in fibromyalgia (Hilton et al., 2017).
    5. Considerations: Ensure engagement.

•  Biofeedback:

    1. Mechanism: Controls autonomic responses, reducing CNS excitability.
    2. Role in Chronic Pain Prevention: Reduces stress-driven chronicity (Nestoriuc et al., 2008).
    3. Protocol: 4–6 sessions over 4–8 weeks.
    4. Evidence: Moderate evidence for fibromyalgia (Nestoriuc et al., 2008).
    5. Considerations: Requires equipment.

3.  Nutrient-Based Treatments:

•  Omega-3 Fatty Acids (EPA/DHA):

    1. Mechanism: Reduce neuroinflammation via resolvins.
    2. Role in Chronic Pain Prevention: Prevents glial-driven sensitization (Calder, 2017).
    3. Protocol: 2,000–3, 000 mg/day for 8–12 weeks.
    4. Evidence: Reduces pain in fibromyalgia (Calder, 2017).
    5. Considerations: Monitor anticoagulant interactions.

•  Magnesium:

    1. Mechanism: Blocks NMDA receptors, reducing excitability.
    2. Role in Chronic Pain Prevention: Inhibits synaptic plasticity (Na et al., 2011).
    3. Protocol: 400–600 mg/day for 4–8 weeks.
    4. Evidence: Reduces pain in migraines (Na et al., 2011).
    5. Considerations: Avoid in renal failure.

•  N-Acetylcysteine (NAC):

    1. Mechanism: Reduces oxidative stress and neuroinflammation.
    2. Role in Chronic Pain Prevention: Prevents sensitization (Pimentel et al., 2020).
    3. Protocol: 600–1200 mg/day for 4–8 weeks.
    4. Evidence: Reduces fibromyalgia pain (Pimentel et al., 2020).
    5. Considerations: Well-tolerated.

•  Vitamin D:

    1. Mechanism: Modulates neuroinflammation.
    2. Role in Chronic Pain Prevention: Reduces sensitization in deficiency states (Helde-Frankling & Björkhem-Bergman, 2021).
    3. Protocol: 2000–4000 IU/day for 8–12 weeks.
    4. Evidence: Reduces fibromyalgia pain (Helde-Frankling & Björkhem-Bergman, 2021).
    5. Considerations: Monitor calcium levels.

Mechanisms of Development of Central Sensitization

  • Synaptic Plasticity: Repeated nociceptive input induces long-term potentiation in dorsal horn neurons via NMDA receptor activation (Woolf, 2010).
  • Glial Activation: Microglia and astrocytes release cytokines (e.g., IL-1β, TNF-α), enhancing neuronal excitability (Ji et al., 2018).
  • Loss of Inhibitory Control: Reduced GABA or glycine inhibition increases pain transmission (Basbaum et al., 2009).
  • Neuroinflammation: Systemic or central inflammation triggers glial priming, perpetuating sensitization (Hutchinson et al., 2010).
  • Descending Facilitation: Enhanced descending pain pathways amplify pain perception (Woolf, 2010).

References:

  1. Woolf, C. J. (2010). Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 152(3 Suppl), S2–S15.
  2. Basbaum, A. I., et al. (2009). Cellular and molecular mechanisms of pain. Cell, 139(2), 267–284.
  3. Ji, R. R., et al. (2018). Pain regulation by non-neuronal cells and inflammation. Science, 354(6312), 572–577.
  4. Hutchinson, M. R., et al. (2010). Non-stereoselective reversal of neuropathic pain. European Journal of Neuroscience, 28(1), 20–29.
  5. Younger, J., et al. (2014). Low-dose naltrexone for fibromyalgia. Arthritis & Rheumatology, 66(6), 1453–1461.
  6. Cohen, S. P., et al. (2018). Ketamine for chronic pain. Regional Anesthesia & Pain Medicine, 43(7), 733–744.
  7. Finnerup, N. B., et al. (2015). Pharmacotherapy for neuropathic pain. Lancet Neurology, 14(2), 162–173.
  8. Chou, R., et al. (2016). Management of postoperative pain. The Journal of Pain, 17(2), 131–157.
  9. Ehde, D. M., et al. (2014). Cognitive-behavioral therapy for chronic pain. American Psychologist, 69(2), 153–166.
  10. Hilton, L., et al. (2017). Mindfulness meditation for chronic pain. Annals of Behavioral Medicine, 51(2), 199–213.
  11. Nestoriuc, Y., et al. (2008). Biofeedback treatment for headache disorders. Applied Psychophysiology and Biofeedback, 33(3), 125–140.
  12. Calder, P. C. (2017). Omega-3 fatty acids and inflammatory processes. Biochemical Society Transactions, 45(5), 1105–1115.
  13. Na, H. S., et al. (2011). The role of magnesium in pain. Magnesium in the Central Nervous System.
  14. Pimentel, M., et al. (2020). N-acetylcysteine in fibromyalgia. Clinical Rheumatology, 39(5), 1613–1621.
  15. Helde-Frankling, M., & Björkhem-Bergman, (2021). Vitamin D in pain management. International Journal of Molecular Sciences, 18(20), 10986.
  16. Hu, S., et al. (2025). Suzetrigine: The first NaV1.8 inhibitor approved for moderate to severe acute pain. Drug Discovery and Therapeutics, 19(1), 80–82.
  17. Lechner, S. M., et al. (2025). Suzetrigine, a non-opioid NaV1.8 inhibitor with broad applicability for moderate-to-severe acute pain. Pain and Therapy.
  18. Jones, J., et al. (2023). Selective inhibition of NaV1.8 with VX-548 for acute pain. New England Journal of Medicine, 389(5), 393–405.
  19. Dolgin, E. (2025). FDA appro Waxman, S. G. (2025). Suzetrigine: A milestone in non-opioid pain management. New England Journal of Medicine.
  20. Vertex Pharmaceuticals. (2025). FDA approval of Journavx (suzetrigine). Vertex Press Release.

Summary and Integration into Acute-to-Chronic Pain Prevention

•  Peripheral Sensitization:

  1. Contribution to Chronic Pain: Sustained nociceptor hyperactivity drives central sensitization, increasing chronic pain risk (e.g., CPSP, CRPS).
  2. Suzetrigine’s Role: As a selective NaV1.8 inhibitor, suzetrigine reduces peripheral nociceptor excitability, decreasing pain intensity within 48 hours and limiting peripheral input that triggers central changes. Its efficacy in postoperative pain (comparable to opioids) and non-addictive profile make it a promising tool to reduce chronicity risk, particularly in surgical and traumatic settings (Jones et al., 2023).
  3. Other Therapies: Gabapentinoids, NSAIDs, topical agents, acupuncture, cold therapy, and nutraceuticals (omega-3s, curcumin, PEA) complement suzetrigine by further reducing inflammation and nociceptor activity.

•  Central Sensitization:

  1. Contribution to Chronic Pain: CNS amplification sustains pain beyond tissue healing, driving chronic conditions like fibromyalgia and CPSP.
  2. Suzetrigine’s Role: Suzetrigine indirectly mitigates central sensitization by reducing peripheral nociceptive input, preventing the initiation of CNS amplification. However, its lack of CNS activity limits its direct effect on established central sensitization, making it most effective in early acute pain management (Lechner et al., 2025). Its role in neuropathic pain is under investigation, but current evidence suggests limited efficacy for chronic pain with central components (Dolgin, 2025).
  3. Other Therapies: Gabapentinoids, LDN, ketamine, duloxetine, CBT, mindfulness, and nutraceuticals (omega-3s, magnesium, NAC, vitamin D) directly target CNS mechanisms, complementing suzetrigine’s peripheral action.

Multimodal Protocol:

•  Post-Traumatic Pain:

    1. Combine suzetrigine (100 mg loading, 50 mg q12h for 7–14 days),
    2. Gabapentinoids, NSAIDs (3–7 days), omega-3s, PEA, and cold therapy to control peripheral sensitization, adding LDN and CBT for high-risk patients to prevent central sensitization.

•  Postoperative Pain:

    1. Use preoperative suzetrigine (100 mg), gabapentin, LDN, omega-3s, and curcumin to preemptively reduce sensitization,
    2. Continuing postoperatively with suzetrigine, PEA, and mindfulness to minimize CPSP risk.

•  Suzetrigine’s Advantages: Non-addictive, comparable efficacy to opioids, and favorable safety profile (no serious AEs in trials) make it a foundational option for acute pain, reducing opioid reliance and chronicity risk (Corrigan-Curay, 2025).

    1. Limitations: High cost ($15.50/pill), limited efficacy in chronic pain (e.g., sciatica), and potential AEs (e.g., itching, rash) require careful patient selection and monitoring (NCThirdAge, 2025).

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.

 

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