Chronic Pain

The short version

●Chronic pain is pain that persists beyond about three months — past normal tissue healing — and often involves changes in how the nervous system processes pain (central sensitization), not just ongoing tissue damage.
●It is bidirectionally linked with depression and anxiety: chronic pain raises the risk of depression, and depression amplifies pain, so treating one without the other often fails.
●First-line care is multimodal: physical therapy and movement, pain-focused psychotherapy (CBT, ACT), non-opioid medications (SNRIs, gabapentinoids, topicals), and interventional options depending on the cause.
●Ketamine is an NMDA-receptor antagonist that targets central sensitization directly; professional consensus guidelines support intravenous ketamine for certain treatment-resistant chronic pain conditions.
●Ketamine is most relevant for centralized or neuropathic pain that hasn't responded to standard care, and for the depression that so often accompanies chronic pain.
●It is not a first-line painkiller and not a substitute for treating the underlying cause; it is one option within a comprehensive plan.

Clinical definition

Chronic pain is generally defined as pain persisting or recurring for more than three months, beyond the expected period of tissue healing. ICD-11 distinguishes chronic primary pain (pain that is itself the condition, such as fibromyalgia or chronic primary low back pain, where central nervous system processing is central) from chronic secondary pain (pain arising from another condition — cancer, neuropathy, osteoarthritis, surgery). A defining feature of much chronic pain is central sensitization: the nervous system becomes hyperresponsive, amplifying pain signals and sometimes generating pain without ongoing tissue damage. This is why chronic pain often does not behave like acute pain and does not respond to the same treatments. Chronic pain is among the most common reasons people seek medical care and is tightly interwoven with mood: depression and anxiety are both common consequences and amplifiers of persistent pain, and the two share overlapping neurobiology.

How it differs from related conditions

vs. Acute pain

A normal, protective response to injury that resolves as tissue heals; chronic pain persists beyond healing and involves nervous-system changes that make it a condition in its own right.

vs. Fibromyalgia

A specific chronic primary pain syndrome of widespread pain with fatigue, sleep, and cognitive symptoms, driven by central sensitization; a subtype of the broader chronic-pain picture.

vs. Neuropathic pain

Pain caused by damage or disease of the nervous system itself (diabetic neuropathy, post-herpetic neuralgia, nerve injury); often burning or electric, and a frequent target for ketamine.

vs. Depression

Chronic pain and depression co-occur so often that each should be screened for when the other is present; pain can be a somatic presentation of depression, and depression worsens pain perception.

First-line treatments

Active physical rehabilitation

Graded exercise, physical therapy, and movement-based approaches are foundational; deconditioning and avoidance worsen chronic pain over time.

Pain-focused psychotherapy (CBT, ACT)

Strong evidence for reducing pain interference and disability by changing the pain-fear-avoidance cycle, independent of changing the pain intensity itself.

Non-opioid medications

SNRIs (duloxetine), gabapentinoids (gabapentin, pregabalin), tricyclics, and topical agents target neuropathic and centralized pain; choice depends on the pain type.

Interventional and procedural options

Injections, nerve blocks, neuromodulation (spinal cord stimulation), and treatment of the underlying structural cause where one exists.

When standard treatments fail

When multimodal care does not control pain, the path forward is to reassess the pain mechanism (is it primarily nociceptive, neuropathic, or centralized?), optimize the rehabilitation and psychological components (often the under-used parts), rotate or combine non-opioid agents, and consider interventional options matched to the diagnosis. Opioids are de-emphasized for chronic non-cancer pain because of limited long-term benefit and significant harms. For centralized and neuropathic pain that remains refractory — and for the depression that frequently accompanies it — rapid-acting glutamatergic options including ketamine enter the conversation, guided by professional consensus.

Where ketamine fits

Ketamine has a more established place in chronic pain than in most psychiatric conditions. As an NMDA-receptor antagonist, it directly targets central sensitization — the amplified nervous-system pain processing that drives many refractory pain states — and professional bodies have issued consensus guidelines supporting intravenous ketamine infusions for certain treatment-resistant chronic pain conditions (Cohen 2018), with the strongest signals in neuropathic pain and complex regional pain syndrome. For Tovani specifically, ketamine's dual relevance matters: many chronic-pain patients also carry a treatment-resistant depression, and ketamine can address both the centralized pain and the mood disorder through related mechanisms. Ketamine is not a first-line analgesic, does not fix structural causes, and is delivered within a comprehensive plan that keeps rehabilitation and psychological care central. The evidence is strongest for centralized and neuropathic pain; for purely nociceptive or structural pain, other treatments are the better fit.

Where this fits with Tovani

Tovani treats chronic pain when it is centralized or neuropathic and has not responded to standard multimodal care, and especially when it co-occurs with treatment-resistant depression — a very common pairing. Eligibility screening captures the pain type, prior treatments, and mood symptoms, and patients are encouraged to continue physical rehabilitation and pain-focused therapy alongside ketamine, because those remain the backbone of durable improvement. Patients whose pain is primarily acute, structural, or surgical are usually better served by treating the underlying cause first; ketamine is for the refractory, centralized end of the spectrum.

Check eligibility How Tovani treats Chronic Pain Find treatment options The science behind ketamine

Frequently asked

Does ketamine actually work for chronic pain?

For certain kinds, yes. Professional consensus guidelines support intravenous ketamine for some treatment-resistant chronic pain conditions, with the best evidence in neuropathic pain and complex regional pain syndrome, because ketamine targets the central sensitization behind those states. It is not a first-line painkiller and works best within a comprehensive plan.

What types of pain respond best?

Centralized and neuropathic pain — pain driven by an over-amplified nervous system or by nerve damage — respond best to ketamine. Purely structural or mechanical pain is usually better treated by addressing its cause.

I have chronic pain and depression — can ketamine help both?

That is a particularly good fit. Chronic pain and treatment-resistant depression frequently coexist and share neurobiology, and ketamine can address both through related mechanisms. Tovani screens for this overlap.

Will I still need physical therapy and other treatments?

Yes. Ketamine does not replace rehabilitation, psychological care, or treatment of the underlying cause — those remain the backbone of durable improvement. Ketamine is one option within the plan, not the whole plan.

References

Cohen SP et al. 2018, Regional Anesthesia and Pain Medicine — Multi-society consensus guidelines on the use of intravenous ketamine infusions for chronic pain. (PMID 29870458)
Sanacora G et al. 2017, JAMA Psychiatry — APA consensus on ketamine's use and safety, relevant to the depression that frequently accompanies chronic pain. (PMID 28249076)
Murrough JW et al. 2013, American Journal of Psychiatry — Ketamine RCT in treatment-resistant depression, the comorbidity that so often coexists with chronic pain. (PMID 23982301)

Last reviewed by Dr. Ben Soffer, DO on May 31, 2026. This page is educational and not a substitute for clinical evaluation. A physician determines whether ketamine therapy is appropriate for your specific situation.