Ketamine in Chronic Pain Management

In recent decades, chronic pain has increasingly been diagnosed, resulting in many patients seeking medical attention. Both pharmacologic and non-pharmacologic therapies are used to treat chronic pain, and an individualized approach tends to be based on trial and error. Irrespective of treatment option, only 30-40% of patients report adequate pain relief. Many patients benefit most from a tailored combination of drugs that target more than one metabolic pathway. Combining therapies can reduce dose requirements of each medication, resulted in fewer side effects and improved analgesia.

Low dose ketamine is being explored for use in treating chronic pain syndromes, especially those with a neuropathic component. Based on a number of clinical trials, many chronic pain syndromes may benefit from ketamine, including migraines, whiplash, fibromyalgia, non-cancer pain, central neuropathic pain, phantom limb pain, complex regional pain syndrome, painful limb ischemia, peripheral nerve injury, neuropathy from chemotherapy, post-herpetic neuralgia, spinal cord injury, temporomandibular pain, and trigeminal neuralgia.

Ketamine was found to produce profound analgesia and amnesia after it was developed in the 1960s as a safer alternative to phenycyclidine. Ketamine is an NMDA receptor antagonist with effects on opioid, muscarinic, and monoaminergic receptors. The mechanism for development of chronic neuropathic pain development includes activation and upregulation of the NMDA receptor from prolonged nociceptive stimulation. As a result, ketamine can produce intense analgesia in syndromes in which neuropathic pain predominates. NMDA antagonists such as ketamine can slow or even stop the excessive barrage of nociceptive input to the brain. Although the potential benefits are clear, there is no consensus on how the drug should be administered for chronic pain management. Duration of infusion may determine the duration of analgesia; therefore, prolonged infusions may be necessary for prolonged effects. Ketamine could be used to reduce or avoid the development of chronic pain syndromes in the first place, such as postoperative pain.

The most effective approaches to treating chronic pain are usually multimodal. Ketamine is usually prescribed and administered in conjunction with opioid analgesics. As an adjunctive treatment, it can reduce opioid requirements, limit nausea and vomiting, and result in improved pain control from opioids. Ketamine is itself an analgesic on its own and can produce synergistic effects when administered with opioids. It also has been shown to help with symptoms of depression, which many chronic pain patients suffer from. Although there are many known potential benefits of ketamine for use in chronic pain management, more evidence from clinical trials is needed to determine its efficacy and administration protocol. Until that is explored further, only after first- and second-line agents such as opioids and antidepressants are shown to be insufficient should ketamine be used for chronic pain patients.

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