Ketamine for Chronic Pain: How it Works

Ketamine, developed more than 50 years ago as a replacement for phencyclidine as a dissociative anesthetic, is the center of attention in various clinical trials for other applications. Studies are finding ketamine to be successful in treating mood disorders, PTSD, as well as moderate to severe acute and chronic pain.

The various success stories involving ketamine makes it one of the most versatile drugs available in anesthesia and possibly in all of medicine, according to published studies. Ketamine is the center of attention in psychiatry as a treatment for depression, a medication to ease various symptoms of anxiety, an option for veterans living with PTSD, as well as one of many alternative treatment options available in psychedelic therapy.

Aside from being at the forefront of new treatment options for addition and mental health conditions, the ability of ketamine to treat a variety of pain disorders is promising. This is especially true in the emergency department as healthcare professionals seek alternatives in the age of the opioid epidemic.

The use of ketamine for pain can extend far beyond the walls of the emergency room. American Society of Anesthesiologists President Dr. John Abenstein once touted ketamine as a miracle drug when administered properly.

What is Chronic Pain?

According to the American Academy of Pain Medicine, more than 1.5 billion people around the world have chronic pain. It’s the most common cause of long-term disability in the United States, affecting nearly 100 million people. There are several ways to classify and categorize chronic pain, but perhaps the most meaningful method is by its type or location. To begin with, pain is considered to be chronic if it lasts more than 12 weeks. Acute pain is a normal sensation triggered in the nervous system to alert you to possible injury and the need to take care of yourself, such as a burn, scrape, cut, broken bone, and more. A severe injury can still be considered acute pain if it is effectively treated, healed, and the pain dissipates. Chronic pain occurs when pain signals keep firing in the nervous system for weeks, months, or in the worst case several years.

Causes of Chronic Pain

Chronic pain is usually caused by an initial injury, such as a sprained back, serious infection, or pulled muscle. Chronic pain can develop from this injury if the nerves become damaged, also known as neurogenic pain. It is also possible for people to experience chronic pain without any initial injury, prior disease, or visible signs of damage to the nervous system. This type of chronic pain is known as psychogenic pain.

Common chronic pain complaints:

• Headache
• Lower back pain
• Pain due to cancer
• Arthritic pain

Common chronic pain causes:

• Chronic fatigue syndrome
• Fibromyalgia
• Interstitial cystitis
• Temporomandibular joint dysfunction (TMJ)
• Inflammatory bowel disease
• Phantom limb pain

Treatment Options for Chronic Pain

Nonsteroidal anti-inflammatory drugs (NSAIDs) are scientifically considered to be ineffective for neuropathic pain. Some of the most common NSAIDs are aspirin, ibuprofen, naproxen, and meloxicam. Ketamine and gabapentinoids (gabapentin and pregabalin) are usually considered to be more effective for neuropathic pain than they are for nonneuropathic pain, according to various studies. However, reality is different than theory. Medications previously considered to be useful for only one type of pain have been shown in clinical trials to be effective for other types of pain. This includes several studies demonstrating ketamine having an analgesic benefit in inflammatory and other types of pain which are not considered to be neuropathic.

In July of 2018, the American Society of Regional Anesthesia and Pain Medicine released its first consensus guidelines for IV ketamine in the treatment of chronic pain. A recent review found the strongest evidence for IV ketamine to be for the treatment of neuropathic pain and complex regional pain syndrome, although the nonneuropathic pain condition they compared them to was fibromyalgia—which is not considered to be a neuropathic pain condition. In addition to fibromyalgia being a particularly challenging condition to treat, the studies cited also utilized lower dosages. There is anecdotal evidence which supports intermediate-term benefit for ketamine infusions for nonneuropathic pain conditions such as headaches and back pain.

How Ketamine Treats Chronic Pain

Ketamine acts on several pathways in the brain that play important roles in pain and mood regulation. Along with the neuropathic pain pathways that ketamine has shown to be beneficial in treating, these other pathways may explain why ketamine may be beneficial in nonneuropathic pain conditions and provide a rationale for its use as a topical pain relief agent. As research from the Yale School of Medicine has found, ketamine triggers glutamate production, prompting the brain to form new neural connections. This could allow the brain to be more adaptable and to create new pathways, which would in turn provide an opportunity to create more positive thoughts and behaviors.

Ketamine may also reduce signals in inflammation (which has been linked to mood disorders in past studies) or help aid communication within certain areas of the brain. A study conducted in 2012 that lasted five years focused on whether or not outpatient IV ketamine infusions were satisfactory for pain relief in patients suffering from various chronic pain syndromes. The authors concluded that for patients with severe refractory pain from multiple causes or conditions, subanesthetic ketamine infusions improved their symptoms. In approximately half of the patients, relief lasted for up to three weeks with minimal side effects.

This potential for a long-term benefit is one of the reasons so many in the field consider ketamine therapy a breakthrough treatment.