Ketamine Therapy for Chronic Pain


Chronic pain and depression have a lot of characteristics in common: they cause enormous socioeconomic burden, they have similar prevalence, and share common treatments.  Chronic pain affects 20% of people worldwide and accounts for up to 20% of physician visits.1

Fibromyalgia and CRPS

Common examples include fibromyalgia and Complex Regional Pain Syndrome.  Fibromyalgia is a condition characterized by widespread musculoskeletal pain thought to be caused by repeated, amplified nerve stimulation that is accompanied by fatigue, sleep, memory, and mood issues.  Complex Regional Pain Syndrome (CRPS) is a form of chronic pain that usually affects an arm or a leg that typically develops after an injury, surgery, stroke, or heart attack.  It is characterized by prolonged or excessive pain and changes in skin color, temperature, and/or swelling in the affected area.  CRPS is divided into 2 categories:  Type 1 (previously known as reflex sympathetic dystrophy syndrome) occurs after an illness or injury that didn’t directly damage the nerves in your affected limb (more common version) and Type 2 (previously known as causalgia) occurs after a distinct nerve injury.  Categorization of chronic pain is important for determining diagnoses and guiding treatment.

Role of Ketamine

While the primary mechanism of action appears to be NMDA receptor antagonism, ketamine also acts on a variety of opioid receptors, antagonizes nicotinic and muscarinic cholinergic receptors, activates D2 dopamine receptors, and facilitates GABA-A signalling.2  A recent review of the published literature found the strongest evidence for intravenous ketamine in the treatment of neuropathic pain and CRPS, where longer durations increased the duration of pain relief.3  Ketamine is ideal for treating posttraumatic and procedure-related pain because it combines unique properties of hypnosis, analgesia, and amnesia. 

The American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists created the Ketamine Guidelines Committee to provide an overview on the use of ketamine infusions to treat acute and chronic pain and establish a framework for standardization.  The consensus guidelines concluded that there was weak evidence supporting ketamine for spinal cord injury (grade C), weak or no evidence for mixed neuropathic pain (including postherpetic neuralgia, phantom limb pain, fibromyalgia, and ischemic pain – grade D), but moderate evidence supporting use in CRPS (grade B).2   

Intravenous ketamine therapy for chronic pain holds much promise.  Based on the above studies, intravenous ketamine therapy for chronic pain follows a separate protocol from mood disorders.  In order to apply the longest possible infusion duration over multiple outpatient visits,  each session is over a period of 4 hours – this maximizes the total dose without causing excessive sedation, and adjunct medications may be used to decrease psychotomimetic side effects.  The latest literature suggests ketamine treatment will not be equally efficacious in all chronic pain conditions.  Unlike other centers, we do not advocate intravenous ketamine for all patients with chronic pain.  Patients with conditions that are less favorable for response can consult with our staff to help examine the cost to benefit ratio in order to determine if intravenous ketamine therapy is appropriate for you.  While these treatments are revolutionary, we recognize that ketamine therapy for chronic pain and psychiatric disorders represent only one part of the multi-modal treatment plan.  We will integrate care with your pain specialist and/or primary care provider to promote the best possible results.

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Awakenings Infusion Center of North Carolina

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  1. Treede R, Rief W, et al. A Classification of Chronic Pain for ICD-11. Pain. 2015 Jun; 156(6): 1003–1007.
  2. Cohen S, Bhatia A, et al. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018; 43: 521-546.
  3. Maher D, Chen L, et al. Intravenous Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization. Anesth Analg. 201; 124: 661-674.