Ketamine and Chronic Pain

Ketamine is a medication that has traditionally been used in surgery and emergency medicine as an anesthetic (a medicine that helps people to be put to sleep during surgery and when they feel severe pain) and analgesic. In recent years, it has also been explored as an option for those living with various chronic pain conditions.

For some patients, ketamine may help reduce pain that has not improved with other treatments. However, it may not be appropriate or safe for everyone, as each person’s body and brain respond differently to this therapy.

 

What Is Ketamine?

Ketamine was developed in the early 1960s and is commonly used in hospitals for anesthesia. In more recent times, ketamine has been explored as a treatment for chronic pain and various mood conditions. Ketamine works differently from other pain medications, and it is usually considered when other options have not provided enough relief.

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How Ketamine Works?

Ketamine may help reduce chronic pain by working on the brain and nervous system in ways that are different from most other pain treatments. One of its main effects is blocking a specific receptor in the nervous system called the N-methyl-D-aspartate (NMDA) receptor, which plays a key role in how pain signals are processed. In people with chronic pain, this system can become overly active, causing the brain to become more sensitive to pain. By calming this overactivity, ketamine may help reduce the intensity and frequency of pain.

It also helps the brain “turn down” pain using natural pain control pathways. These are sometimes called top-down pathways or descending pain pathways, meaning the brain sends signals down the spinal cord to reduce pain coming from the body. In people with long-term pain, this system often stops working well. Ketamine may help “reboot” this system so the body can better manage pain on its own.

In addition, ketamine may lower nerve inflammation and improve mood by affecting certain brain chemicals related to both pain and emotional well-being. Together, these effects can make it easier to manage chronic pain, especially when other treatments have not been effective.

What Conditions It May Help?

Ketamine has been studied and safely used for many years to treat short-term severe (acute) pain, especially after surgery or in emergency settings. It can help reduce pain quickly and may lower the need for opioids in these situations although evidence is still limited.

In recent years, ketamine has also been explored for chronic (long-lasting) pain, particularly in people who have not found relief with other treatments. While research is still ongoing, some people may benefit from ketamine in specific situations, including:

Neuropathic pain and complex regional pain syndrome (CRPS): These conditions share the common feature of an increased activation of NMDA receptors in the nervous system thereby causing an increase in pain

*Ketamine is not commonly used for muscle or joint pain and is not a cure for chronic pain. As with other chronic pain medications, ketamine may be considered in combination with other management strategies such as self-management strategies, psychological interventions and movement.    

How Is Ketamine Given?

Ketamine is typically offered under careful medical supervision in specialized clinics or hospitals. Different ways of giving ketamine include:

  • PAIN: High Dose IV Infusion

    This is the most common and studied route for administering this medication. Prior to being considered for high dose IV ketamine, a thorough clinical assessment of your medical and psychological history by pain physician and psychologist is required to ensure that IV ketamine is safe for you.  It is delivered slowly through a vein over a few hours in a controlled clinical setting with close monitoring. Close monitoring is required to manage any potential side effects from the infusion such anxiety, hallucinations, high blood pressure and rapid heart rate. The infusions may be repeated in some situations.

  • Low Dose Short Duration IV Infusions

    The evidence for pain benefits using this type of infusion is limited.

  • Other

    There are also oral and topical ketamine formulations, although the evidence around them is limited and not frequently used.  Oral formulations have limitation in that the body has a harder time absorbing it and only a small amount actually makes it into your system. Ketamine is a controlled substance, and requires a written prescription for oral ketamine.

    A specific form of ketamine called esketamine (brand name Spravato®) is approved in Canada for treatment‑resistant depression.

 

 

Risks and Side Effects?

While some people may experience meaningful pain relief with ketamine, it can also cause side effects. The likelihood and severity depend on the dose, how often it is used, and your past medical history.

  • Common Short-Term Effects

    These effects may occur shortly after a dose is given, even at low doses and usually subside within a few hours:

    • Dizziness or lightheadedness
    • Feeling “disconnected", "floaty” or having vivid dreams or hallucinations
    • Stomach discomfort (i.e., nausea, vomiting, diarrhea)
    • Blurred vision or dry mouth

  • Less Common But Serious Effects

    • Kidney/Liver: Urinary tract infections, and/or liver dysfunction
    • Allergic: anaphylaxis and angioedema.
    • Cardiovascular: Transient increases or decreases in blood pressure, worsening of heart failure in patients with heart failure, and irregular heart rhythms
    • Gastrointestinal: Loss of appetite, nausea, and vomiting.
    • Muscular: Muscle stiffness and spasms or tonic-clonic movements resembling seizures and enhanced skeletal muscle tone
    • Ophthalmologic: double vision, uncontrollable eye movements, and increased intraocular pressure.
    • Psychiatric: Amnesia, anxiety, confusion, depression, disorientation, dysphoria, dissociative state, hallucinations, flashbacks, unusual thoughts, extreme fear, excitement, irrational behavior, and insomnia. 
    • Respiratory: Apnea, increased laryngeal and tracheal secretions, laryngospasm, and respiratory depression.
    • Skin: Injection site reactions (infrequent), local pain, rash.
    • Other: Dependance and misuse
 

 

Harms Reduction with Ketamine

Driving: Driving or operating machinery while under the influence of ketamine can increase the risk of injury to the user and to others.  Ketamine can reduce your reaction time, impair your psychomotor and visual function.  As such it is recommended that one not drive the day of ketamine.

Who Might Benefit?

Ketamine treatment is not for everyone, but it may be offered to people whose pain and health profile match specific clinical criteria.

Here's who’s may be considered for Ketamine:

  • Refractory neuropathic pain
  • Complex Regional Pain Syndrome (CRPS)

Here are health conditions where Ketamine may be unsafe or not effective:

  • Active substance use disorder
  • Unstable mental health (i.e active suicidality or self-harm behavior, schizophrenia, psychosis, PTSD)
  • Generalized pain condition (fibromyalgia or myofascial pain syndrome)
  • Unstable cardiac disease
  • Severe liver dysfunction
  • Glaucoma
  • Hyperthyroidism
  • Pregnancy or breast feeding
  • Poorly controlled blood pressure
 

 

Self-Management and Other Supports

Ketamine is not a cure for chronic pain. For most people, it provides temporary relief and works best when combined with other strategies that support long-term well-being. These include:

  • Physiotherapy
  • Cognitive Behavioural Therapy (CBT), mindfulness, or pain coping strategies
  • Sleep support and routine-building
  • Pain education and pacing strategies
  • Nutrition, peer support, and goal setting
 

 

References and Resources

76 Grenville St. Toronto, ON M5S 1B2 Canada

TAPMI Hub Clinic

Phone: 416-323-6269 Office Fax: 416-323-2666 Hours: 8:00 a.m. – 4:00 p.m. Monday – Friday

Administration

Dr. Tania Di Renna, Medical Director Sandra Robinson, Administrative Director