Ketamine in Acute and Chronic Pain Management

Acute and chronic pain remain important health problems in the United States and worldwide. With the rise in the prevalence of many chronic degenerative diseases across the globe, the distribution and absolute numbers of persons experiencing acute and chronic pain have continued to increase. As a result, pain management has come to the forefront of the public health community. The manifestation of pain itself typically involves the peripheral and central nervous systems. Pain can be classified as nociceptive, neuropathic, or nocicplastic in origin. Nociceptive pain, also known as physiologic pain, results from the activation of primary nociceptive afferents by actual or potential tissue-damaging stimuli. In nociceptive pain, large nerve integrity remains preserved as sensory receptors are stimulated within visceral and somatic structures. In contrast to nociceptive pain, neuropathic pain results from direct injury or disease affecting the somatosensory system and tends to be more disabling than nociceptive pain.  Neuropathic pain subdivides into peripheral (e.g., diabetic neuropathy) and central (e.g., spinal cord injury or central poststroke pain), while nociceptive pain subcategorizes into somatic or visceral (e.g., inflammatory bowel disease). Recently, the International Association for the Study of Pain added a third category to the pain classification of taxonomy for conditions that do not neatly fit into neuropathic or nociceptive categories. Nociplastic pain refers to pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage or evidence of a disease or lesion directly affecting the somatosensory system. Conditions considered to be nocicplastic pain include fibromyalgia, complex regional pain syndrome (CRPS) type I, and irritable bowel syndrome. One should keep in mind that several pain conditions, such as failed back surgery syndrome, contain elements of more than one pain category and can be classified as “mixed” pain states. In addition, conditions clearly classified as nociceptive and neuropathic often contain overlapping mechanisms with nocicplastic pain in that they involve abnormal nociceptive processing (e.g., amplified pain signals, expansion of receptive fields, decreased descending modulation).  Pain can also categorize as acute, chronic, or a combination of these types (e.g., sickle cell crisis). Acute pain arises from a specific disease or injury, and its duration is typically self-limited. Acute pain is considered a protective biological purpose and is often associated with muscle spasms and sympathetic nervous system activation. In contrast, chronic pain may be regarded as a disease state, with its duration outlasting the normal healing time associated with disease or injury. Chronic pain may also stem from psychological states and does not serve an apparent biological purpose. Unlike the self-limited nature of acute pain, chronic pain often does not have a recognizable endpoint. Ketamine is an N-methyl-D-aspartate (NMDA) antagonist. It was approved for use as a dissociative anesthetic agent to provide analgesia in acute pain. In recent years it has been used as a non-opiate alternative for chronic pain syndromes such as complex regional pain syndrome (CRPS), neuropathic pain, and other intractable chronic pain states. Ketamine use has also been expanded to nonanalgesic uses as well. The United States Food and Drug Association approved intranasal ketamine to treat resistant unipolar depression and suicidal ideations. Ketamine has also been used for its bronchodilatory properties in patients with severe asthma exacerbation as a temporizing measure to prevent mechanical ventilation. Ketamine use, however, is not without issues. Ketamine toxicity is a well-documented phenomenon, and hepatobiliary dysfunction has been reported with recurrent ketamine use. This activity will review the indications and clinical issues to consider when using ketamine to manage acute and chronic pain.