Ketamine for Chronic Pain: Is It Beneficial?

Chronic pain is a leading cause of disability, but there is currently a lack of effective treatments. Doctors may prescribe antidepressants, anti-seizure drugs, or opioids, but these only provide adequate relief in 30–40% of cases.

This shortcoming has led scientists to investigate alternatives, including ketamine for chronic pain. So, can it offer any additional benefits in comparison to traditional painkillers? Let’s take a look.

Ketamine Treatment for Chronic Pain

There is a growing body of research on the topic of ketamine and chronic pain. Although the evidence is still somewhat inconclusive, studies suggest that it may be helpful in some cases. It appears that ketamine could be especially useful for pain with a neuropathic component.

This is due to the way that ketamine interacts with the central nervous system. It inhibits receptors known as N-methyl-D-aspartate (NMDA) receptors. They are densely concentrated in the brain and spinal cord and bind with the neurotransmitter glutamate. Glutamate is the primary excitatory neurotransmitter, meaning that it increases nervous system activity.

NMDA receptors play a vital role in the pathology of chronic pain. One of their functions is passing nerve signals between the body and the brain. In chronic pain, NMDA receptors become upregulated, meaning that their activity increases. This increased activity amplifies the intensity of pain signals; a phenomenon called central sensitization.

One of the ways ketamine works is by temporarily blocking NMDA receptor activity. Some experts believe that it allows the nervous system to ‘reset’ itself, reducing central sensitization.

It seems that ketamine could provide further benefits by binding with other receptors, including opioid receptors, to relieve pain. Moreover, it could help to reduce opioid tolerance.

It also affects receptors called innate repair receptors, which influence tissue repair and inflammation.

Finally, ketamine exhibits potent antidepressant properties. Since chronic pain and depression often exist side by side, improving one may significantly benefit the other. For example, reducing depression may alter individuals’ pain perception and make it easier to cope. Likewise, alleviating pain symptoms may help to reduce depression.

What Is Ketamine Infusion for Chronic Pain?

There are several different ketamine administration methods. One of the most common is intravenous infusion. It involves slowly injecting ketamine into a vein over several hours.

Ketamine infusion for chronic pain appears to be superior to other administration methods. For example, oral ketamine has low bioavailability, meaning that the body cannot absorb it efficiently. Furthermore, injection into the spinal cord can cause neurotoxicity and damage the nervous system.

However, there are some significant drawbacks to ketamine infusion therapy for chronic pain. For example, research suggests that treatment is most effective when individuals receive a course of low-dose infusions over several days.

There are a growing number of ketamine clinics across the USA, offering infusions on an outpatient basis. Nevertheless, visiting a clinic daily for hours at a time is not particularly convenient.

There are a growing number of ketamine clinics across the USA, offering infusions on an outpatient basis.

Moreover, although low-dose ketamine is well-tolerated in clinical settings, the risk of side effects increases with higher doses. Ketamine’s possible side effects include:

  • Sedation
  • Paranoia
  • Anxiety
  • Dizziness
  • Vertigo
  • Blurred vision
  • Nausea and vomiting
  • Abnormal speech and movement
  • Vivid dreams or nightmares
  • Memory problems
  • Increased heart rate and blood pressure
  • Elevated liver enzymes
  • Liver damage

Unfortunately, there is no consensus regarding the optimal ketamine infusion dose for chronic pain. Therefore, prospective patients must carefully weigh the risk of side effects against the potential benefits.

Ketamine for Chronic Pain: Panacea or Snake Oil?

There are several questions surrounding the effectiveness of ketamine treatment for chronic pain.

There is no standard dosage, and the ketamine infusion for chronic pain success rate is highly variable. There are several published reviews on the subject, but most have failed to reach a definitive conclusion.

Most studies show that ketamine’s pain-relieving properties peak during the infusion itself. It may be possible to extend these effects over several days or weeks with repeated infusions. However, the number of infusions necessary to achieve this is unclear.

Some studies suggest that 10 hours of infusions could provide some benefit. Meanwhile, others state that as many as 100 hours may be necessary to achieve favorable results.

Far more research is necessary before we can confirm ketamine’s effectiveness for chronic pain. Below is a summary of the evidence that is currently available.

Ketamine in Chronic Pain Management: An Evidence-Based Review

Researchers have investigated ketamine for the treatment of numerous chronic pain conditions. So far, it seems to only be truly effective for one or two.

To date, ketamine infusion for chronic pain research has focused on:

  • Chronic neuropathy
  • Complex regional pain syndrome (CRPS)
  • Peripheral nerve injury
  • Spinal cord injury
  • Limb ischemia
  • Migraine
  • Fibromyalgia

According to guidelines published in 2018, ketamine may be most effective for CRPS. The document presents moderate evidence that 4–10 days of infusions could provide up to 12 weeks of pain relief.

It also states that there is weak evidence that ketamine could provide short-term relief for spinal cord injury. However, there is currently not enough evidence to support ketamine use for the remaining conditions.

The document also provides an overview of the existing evidence relating to infusion time, stating:

  • 2 hours: Unlikely to provide pain relief for more than 48 hours
  • Over 10 hours: 95% chance of 50% pain relief for more than 48 hours
  • Over 30 hours: 99% chance of 50% pain relief for more than 48 hours

However, it is unclear whether these figures relate to cumulative or continuous hours. The authors suggest that performing repeat infusions before the effects of the previous one dissipate may be useful.

A 2019 systematic review and meta-analysis concluded that ketamine infusions provide significant but short-term pain relief. Its authors suggest that physicians assess patients on a case-by-case basis to determine whether ketamine may be beneficial.

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