February 14, 2024

The Science Behind Ketamine Therapy for Pain

Ketamine Therapy for Pain



The cause of pain is extremely complex, involving overlapping mechanisms and multiple sources. That’s why it’s important to understand the different types of pain. This includes, but is not limited to, acute (short-term) vs chronic (long-term), and whether the pain is caused by things like tissue damage (nociceptive) or nerve issues (neuropathic).


In IV ketamine clinics, the main goal is to assist in the treatment of chronic pain, which is defined as pain persisting for at least three months, in contrast to acute pain, which may result from a direct injury and is more immediate. While ketamine is commonly employed in hospital settings for acute pain management, our mission at Mind Body Centers is to help relieve chronic pain. Thus, this article will focus on chronic pain.


Pain is further classified by the source of damage causing the pain. For example, pain caused by tissue damage is called nociceptive pain. Nociceptive pain is then divided into two categories, either somatic (related to injuries to muscles, bones and connective tissues) or visceral (related to organ injury). In contrast, pain resulting from nerve damage is called neuropathic pain. Keep in mind that some pain diagnoses, i.e. fibromyalgia, can have involvement of both neuropathic sources and nociceptive sources. Since the majority of nociceptive pain is acute, we will focus on chronic neuropathic pain for this article.

Nociceptive vs Neuropathic

Ketamine Decreases Nociceptive and Neuropathic Pain Through The NMDA Receptor

If you read part-one about how ketamine improves mental health, you will see many parallels in what it does for pain. For starters, ketamine improves pain by antagonizing the NMDA receptor, resulting in a surge of glutamate. The NMDA receptor is present on the spinal cord and also in the brain, specifically the hippocampus. With chronic pain, studies have shown there is over activation of the NMDA receptor causing increased pain signals to the brain (also called “central sensitization”). However, by blocking the NMDA receptor, ketamine halts the significant increase in pain signals reaching the brain, thereby reducing pain.


What This Means For Your Specific Pain Diagnosis

The NMDA receptor plays a major role in chronic pain. In this article, we will examine how ketamine affects certain pain diagnoses, focusing on the three most common conditions treated in our clinic: fibromyalgia, migraine headaches, and CRPS (Complex Regional Pain Syndrome).


Fibromyalgia is a chronic musculoskeletal pain or nociceptive hypersensitivity including symptoms like fatigue, pain and stiffness. The exact etiology of fibromyalgia is unknown, but studies have shown a relationship between fibromyalgia and activation of the NMDA receptor. This hypersensitivity can be stopped in its tracks through ketamine’s ability to antagonize the NMDA receptor.


While migraine headaches can develop without a diagnosis of fibromyalgia, patients with fibromyalgia can also develop migraine headaches, another form of chronic pain that we commonly treat at Mind Body Centers. By blocking neurotransmitters from reaching the NMDA receptors, pain signals related to migraine headaches cannot be sent and therefore the pain severity decreases significantly.


Another pain diagnosis commonly treated by our clinic is CRPS, or Complex Regional Pain Syndrome. This condition is characterized by chronic, excruciating pain, typically affecting one arm or leg. Additional symptoms include skin color changes, swelling (edema), nail or hair changes, and limitations in movement. CRPS pain typically arises following an injury to a peripheral nerve (known as CRPS type II) or after a traumatic injury that doesn’t involve obvious peripheral nerve damage (known as CRPS type I). The overactivity of nerve fibers in CRPS is believed to be linked to the activation of the NMDA receptor. Therefore, given that ketamine is known to block this receptor and inhibit its firing, it leads to a decrease in pain.


Pain Pathways

Outside of the NMDA receptor, ketamine also reduces pain signals through inhibiting the descending pain pathway. In order to describe this pathway, I have provided an example:


Let’s say a person falls off their bike and injures their right arm. Because of this injury, cells become damaged and release “prostaglandins” or hormone-like molecules that affect different body functions. These prostaglandins then carry a signal up the ascending pathway to the spinal cord, and then the signal is transferred from one neuron to another, up to the brainstem and brain. Once in the brain, a sensation of pain is felt.


The descending pathway basically controls, or inhibits, the ascending pathway from causing the stimulus to travel up to the brain resulting in the sensation of pain. By acting on neurons in the brainstem and spinal cord, pain signals are stopped from traveling up to the brain and therefore the sensation of pain does not occur.


Ketamine for Pain pathway

FUN FACT: the pain stimulus always occurs on the opposite side of the brain for where the pain actually stems from (i.e. the left side of your brain will receive a stimulus after you injure your right arm)


Decreasing Pain Through Inhibitory Pathways & Opioid Receptors

Patients struggling with chronic pain are often unable to activate the descending pain inhibition pathway, and are therefore unable to stop this sensation of pain. Interestingly, one way opioids act to reduce pain signals is also by activating these inhibitory descending pathways.


Another, more commonly understood method through which opioids reduce pain is by activating opioid receptors. Interestingly, ketamine also acts on certain opioid receptors.


The advantages of ketamine over opioids for pain treatment include its non-daily administration, lack of demonstrated physical and psychological dependence, far fewer side effects, and ketamine’s potential to repair damaged neurons, whereas opioids merely just “numb the pain”.


Anti-inflammatory Effects

Finally, inflammation in the body requires a very well balanced homeostatic system. Some inflammation is good for fighting off disease and wound healing, but too much inflammation can be harmful. With chronic pain, there are often high levels of “bad” inflammation. Fortunately, ketamine has been shown to reduce inflammation through balancing cytokine (mediators of inflammation) response, without affecting the local inflammatory process, making it a great medication choice for pain management.


Pain and Mental Health Overlap

Unfortunately, individuals with chronic pain are also at an increased risk for depression and other related mental health disorders. A study from the American Psychiatric Association reported approximately 35-45% of individuals with chronic pain also reported experiencing depression. While that number may seem high, other studies have reported upwards of 85%. A benefit of ketamine compared to other pain management techniques, is that it targets depression and mental health disorders as well. Specifically, See part one for a detailed explanation of ketamine for mental health disorders.




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