Chronic pain affects an estimated 24.3% of U.S. adults, and 8.5% experience high-impact chronic pain that frequently limits daily life or work — yet for many of those individuals, standard pharmaceutical approaches such as opioids, anticonvulsants, and nerve blocks provide incomplete or diminishing relief over time (Lucas & Sohi, 2024). If you are living with complex regional pain syndrome, neuropathic pain, fibromyalgia, or another condition that has resisted conventional treatment, you are not alone in your frustration, and there are reasons rooted in neuroscience to explain why standard analgesics often fall short. At our Princeton, NJ location, we offer IV ketamine therapy as a medically supervised option for appropriate chronic pain conditions.
Why Chronic Pain Is So Difficult to Treat
Pain is not simply a signal from an injured tissue — it is a dynamic, complex experience shaped by the central nervous system itself. In many chronic pain conditions, a process called central sensitization occurs, in which the nervous system becomes hyperexcitable and begins amplifying pain signals far beyond what the peripheral injury, if any, would predict (Woolf, 2011). This central amplification explains why so many chronic pain patients experience pain that is disproportionate to visible tissue damage and why targeting the periphery alone with standard analgesics often provides only partial relief.
Characteristics of centrally sensitized chronic pain:
Allodynia: Normally non-painful stimuli — light touch, clothing contact — are perceived as painful.
Hyperalgesia: Painful stimuli produce an exaggerated pain response.
Temporal summation: Repeated stimuli produce progressively greater pain responses.
Widespread pain: Sensitivity spreads beyond the original injury site.
Comorbid depression and anxiety: Central sensitization shares overlapping neural mechanisms with mood disorders, which is why pain and depression so frequently co-occur.
This neurological underpinning is precisely why ketamine — a drug that acts centrally on specific receptors — has been studied as a treatment for chronic pain conditions that have a central sensitization component. One barrier to accessing ketamine for pain is awareness: many patients and even their pain specialists may not know that IV ketamine is an option.
How Ketamine Addresses Central Sensitization
Ketamine’s primary mechanism of action — antagonism of the NMDA receptor in the glutamate system — is directly relevant to central sensitization. NMDA receptors in the dorsal horn of the spinal cord and in supraspinal pain-processing centers are central to the “wind-up” phenomenon that drives sensitization (Cohen et al., 2018). When ketamine blocks these receptors, it may help interrupt the cycles of amplification that perpetuate chronic pain independent of ongoing tissue damage.
Beyond acute NMDA blockade, subanesthetic ketamine infusions also appear to interact with multiple receptor systems and neuroinflammatory pathways implicated in chronic pain states (Cohen et al., 2018). This multi-modal pharmacological profile may explain why ketamine reaches pain conditions that more targeted agents do not. IV ketamine for chronic pain is an off-label use for most conditions — while it is used in clinical practice based on an evidence base and physician judgment, it has not received a formal FDA indication specifically for chronic pain management. Results vary by individual, and realistic expectations are essential.
To better understand how ketamine infusions work at the neurological level, see our overview of ketamine infusions for chronic pain in Princeton.
What the Research Shows for Specific Pain Conditions
The evidence base for IV ketamine in chronic pain varies by condition. For complex regional pain syndrome (CRPS), the evidence is among the strongest. A randomized controlled trial by Sigtermans et al. (2009) found that continuous subanesthetic ketamine infusions reduced pain intensity in CRPS patients compared to placebo, with effects lasting beyond the infusion period. Consensus guidelines on IV ketamine for chronic pain also note stronger support for CRPS than for several other chronic pain indications, while emphasizing that evidence varies by condition and dose range (Cohen et al., 2018).
For fibromyalgia, a condition characterized by widespread musculoskeletal pain with strong central sensitization features, the literature suggests possible short-term benefit, though long-term durability and optimal protocols remain less certain (Pastrak et al., 2021). For neuropathic pain from conditions such as diabetic neuropathy, post-herpetic neuralgia, and phantom limb pain, controlled trials and systematic reviews have shown variable but sometimes meaningful analgesic benefits (Orhurhu et al., 2019). Discuss with your provider whether the current evidence supports pursuing ketamine for your particular diagnosis and what realistic outcomes might look like for your situation.
The IV Ketamine Experience for Pain at Allevate Health Princeton
Managing chronic pain with ketamine involves a somewhat different protocol than managing depression. Pain infusions may use different dosing schedules, longer infusion durations, or a different number of sessions compared to standard psychiatric protocols. At our Princeton, NJ location at 707 State Road Suite 105, we build each treatment plan around your diagnosis, response, medical history, and goals for function.
What to expect in your care:
Complimentary consultation: We review your pain history, diagnosis, prior treatments, including opioids, nerve blocks, physical therapy, and other interventions, and your goals for pain management.
Individualized protocol: Dosing, infusion duration, and the number and frequency of sessions are tailored to your specific condition and response.
Vital sign monitoring: Blood pressure, heart rate, and oxygen saturation are monitored during each infusion; ketamine can transiently elevate blood pressure, which our team is trained to manage.
Medication review: We review current pain medications and coordinate with your pain management specialist or primary care provider when appropriate.
A second common barrier for chronic pain patients is concern about the interaction between ketamine and existing opioid medications. Notably, some research suggests ketamine may help reduce opioid requirements in certain settings, but this requires careful medical management — do not adjust opioid doses without explicit guidance from your providers.
If depressive symptoms are also part of your clinical picture, we can discuss whether a mood-focused option such as SPRAVATO® treatment in Princeton, NJ or another treatment may be appropriate. SPRAVATO® is FDA-approved for treatment-resistant depression and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior; it is not FDA-approved for chronic pain (U.S. Food and Drug Administration, 2025). To learn more about our services and schedule your complimentary consultation, please contact us or call 640-252-9785.
Frequently Asked Questions
Q: Is IV ketamine approved by the FDA for chronic pain?
A: IV ketamine for chronic pain is an off-label use. Ketamine is FDA-approved as an anesthetic agent, and its use in subanesthetic doses for pain management is based on clinical evidence and physician judgment outside of formal FDA-approved pain indications (DailyMed, n.d.). SPRAVATO® is FDA-approved for treatment-resistant depression and certain depressive symptoms, not pain.
Q: Which chronic pain conditions respond best to IV ketamine?
A: The strongest evidence exists for CRPS and some neuropathic pain conditions with a significant central sensitization component. Fibromyalgia and some phantom limb pain conditions also have supporting evidence, though the strength of evidence varies. Response depends on the individual, diagnosis, and treatment protocol.
Q: How long do the pain-relieving effects last after a ketamine infusion series?
A: Duration of benefit varies considerably. Some patients report relief for weeks to months after a series; others experience shorter windows. Maintenance infusions may be an option for patients with a good initial response. Results vary by individual.
Q: Will ketamine help with pain if I am currently taking opioids?
A: Opioids do not necessarily prevent a ketamine response, and ketamine has been studied as an adjunct in pain care. However, opioid interactions require careful management. A thorough medication review at your consultation is essential.
Q: Is ketamine treatment for pain covered by insurance?
A: Coverage for ketamine for chronic pain is variable, and IV ketamine for pain is often not covered because it is off-label. We discuss financial considerations and available options during your complimentary consultation so you can make an informed decision.
Key Takeaways
Chronic pain affects an estimated 24.3% of U.S. adults, and central sensitization underlies many treatment-resistant cases where conventional analgesics fall short (Lucas & Sohi, 2024; Woolf, 2011).
Ketamine’s NMDA receptor antagonism targets mechanisms involved in central sensitization — a different approach from opioids and many conventional analgesics.
Randomized controlled evidence supports IV ketamine for CRPS, while supporting evidence for fibromyalgia, neuropathic pain, and other central sensitization conditions continues to evolve (Cohen et al., 2018; Sigtermans et al., 2009).
IV ketamine for chronic pain is off-label; individual results vary, and treatment protocols differ from psychiatric applications.
At our Princeton, NJ location, we provide individualized IV ketamine treatment for chronic pain in a medically supervised setting, beginning with a complimentary consultation.
References
Cohen, S. P., Bhatia, A., Buvanendran, A., Schwenk, E. S., Wasan, A. D., Hurley, R. W., Viscusi, E. R., Narouze, S., Davis, F. N., Ritchie, E. C., Lubenow, T. R., & Hooten, W. M. (2018). Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia and Pain Medicine, 43(5), 521–546. https://doi.org/10.1097/AAP.0000000000000808
Lucas, J. W., & Sohi, I. (2024). Chronic pain and high-impact chronic pain in U.S. adults, 2023. National Center for Health Statistics Data Brief, No. 518. Centers for Disease Control and Prevention. https://doi.org/10.15620/cdc/169630
Orhurhu, V., Orhurhu, M. S., Bhatia, A., & Cohen, S. P. (2019). Ketamine infusions for chronic pain: A systematic review and meta-analysis of randomized controlled trials. Anesthesia & Analgesia, 129(1), 241–254. https://doi.org/10.1213/ANE.0000000000004185
Pastrak, M., Abd-Elsayed, A., Ma, F., Vrooman, B., & Visnjevac, O. (2021). Systematic review of the use of intravenous ketamine for fibromyalgia. The Ochsner Journal, 21(4), 387–394. https://doi.org/10.31486/toj.21.0038
Sigtermans, M. J., van Hilten, J. J., Bauer, M. C., Arbous, M. S., Marinus, J., Sarton, E. Y., & Dahan, A. (2009). Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain, 145(3), 304–311. https://doi.org/10.1016/j.pain.2009.06.023
U.S. Food and Drug Administration. (2025). SPRAVATO® (esketamine) nasal spray, CIII prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf
Woolf, C. J. (2011). Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 152(3 Suppl), S2–S15. https://doi.org/10.1016/j.pain.2010.09.030
Medical Disclaimer
The information in this blog is for educational purposes only and does not constitute medical advice. Ketamine therapy, SPRAVATO®, and treatment should only be pursued under the supervision of a licensed provider familiar with your full medical and psychiatric history. Individual results vary. If you are experiencing a mental health crisis or thoughts of self-harm, please call or text 988 to reach the Suicide and Crisis Lifeline or go to your nearest emergency room.