Over the last few decades, chronic pain has become one of the most common reasons people seek medical attention including anesthesia services. Treatment for chronic pain includes both pharmacologic and non-pharmacologic therapies and tends to be based on a trial and error approach applied to each individual patient. Unfortunately, regardless of which treatment is selected, only 30-40% of patients demonstrate adequate-to-good pain relief. For many patients, using a combination of drugs that target more than one pain pathway can reduce dose requirements of each drug and result in better analgesia with fewer adverse effects. Ketamine in low doses can be used to treat chronic pain syndromes, especially those with a neuropathic component. Based on several randomized controlled trials, chronic pain syndromes that may benefit from ketamine usage include the following: migraines, breakthrough non-cancer pain, central neuropathic pain, chemotherapy-induced neuropathy, complex regional pain syndrome, fibromyalgia, painful limb ischemia, peripheral nerve injury, phantom limb pain, post-herpetic neuralgia, spinal cord injury, temporomandibular pain, trigeminal neuropathic pain, and whiplash.
Ketamine was first developed in the 1960s as a safer alternative to phenycyclidine and subsequently was found to produce profound analgesia and amnesia. Ketamine acts as an NMDA receptor antagonist with some effects on opioid, muscarinic, and monoaminergic receptors. An important mechanism of chronic neuropathic pain development includes activation and upregulation of the NMDA receptor from prolonged nociceptive stimulation; thus, ketamine can produce strong analgesia in neuropathic pain states. There is evidence that NMDA antagonists such as ketamine can stop the onslaught of nociceptive input to the brain and provide an alternative to existing treatments of chronic pain syndromes. Despite its known potential benefits, there is no consensus on the administration protocol. Duration of infusion may determine the duration of analgesia, and long term infusions of ketamine may be required for lasting analgesia following treatment. Ketamine could even be used to reduce chronic pain development in the first place, such as that which may occur following surgery.
Multimodal approaches to treating chronic pain are often the most effective. Ketamine is often administered in conjunction with opioid analgesics and can reduce opioid requirements, reduce associated nausea and vomiting, and improve the efficacy of opioid treatment. Ketamine is an analgesic itself and can be additive or synergistic when interacting with opioids. It also has potent antidepressant qualities, which may greatly benefit many chronic pain patients who cope with depressive symptoms. Despite the many potential benefits of ketamine for use in chronic pain management, more evidence is needed to determine its efficacy, and therefore ketamine should be considered only if first- and second-line agents such as opioids and antidepressants are not effective.