Complex Regional Pain Syndrome (CRPS)

Complex Regional Pain Syndrome (CRPS) is a pain condition that develops following injury to a peripheral nerve (type II) or following trauma without obvious peripheral nerve damage (type I) (Pickering & McCabe, 2014). Symptoms include pain, edema, changes in skin temperature and color, and hyperhidrosis. Many individuals with CRPS develop chronic pain that affects their quality of life and functional capacity. Currently, most patients with CRPS are treated through trial and error, trying opioids, anti-neuropathic pain medications, and nerve blocks to lessen their symptoms. However, many individuals are left disappointed by this method, complaining of long-term severe pain and disability (Pickering & McCabe, 2014). CRPS is attributed to NMDAR upregulation in the spine (central sensitization), leading to increased pain signaling, allodynia, and hyperalgesia (Sigtermans et al., 2009). Since Ketamine is an NMDAR antagonist, it has been considered for treatment of CRPS.

By blocking NMDA receptors, Ketamine is able to provide long term relief for individuals with CRPS. Sigtermans et al. (2009) showed that CRPS type 1 patients received long term relief for up to 3 months following a 100h infusion of Ketamine. In a study performed by Pickering & McCabe (2014), individuals with Chronic Regional Pain Syndrome were intermittently given subanesthetic levels of Ketamine over the course of 10 days. These patients reported reduction in pain that persisted for weeks, only losing potency after 10 weeks (Pickering & McCabe, 2014). Similarly, in a double-blind, randomized, placebo-controlled trial, individuals with Chronic Regional Pain Syndrome were given a 4.2 day infusion of either Ketamine (22.2 ± 2.0 mg/h/70 kg by the final infusion) or placebo. Those that received Ketamine saw a larger reduction in pain, as indicated by their pain scores throughout the 12-week study (Sigtermans, et al. 2009). Although the analgesic effects of the Ketamine infusions lasted for about 10 weeks, participants denied improvement in their functional statuses, noting that their activity levels did not increase (Sigtermans, et al. 2009). Repetitive infusions may be necessary to maintain the effects of Ketamine while enhancing an individual’s quality of life.

Although Ketamine also affects nicotinic and opioid receptors, it is likely that both the anaesthetic and the analgesic qualities of Ketamine are due to its actions as an NMDA receptor antagonist. The analgesic effects of Ketamine can persist for longer than the drug’s expected half-life, indicating that Ketamine may also succeed by suppressing neural sensitization in pain circuits. Ketamine may reset previously sensitized nociceptive circuits, providing benefits to patients long after the infusion has worn off (Pickering & McCabe, 2014).

Although these studies have indicated that Ketamine provides long term pain relief to individuals with CRPS, they have also identified some side effects associated with Ketamine infusions. Some participants experienced psychomimetic effects, endorsing hallucinations and drug high (Sigtermans, et al. 2009). In another study, some individuals displayed signs of hepatic dysfunction, with half of the subjects of one study developing elevated liver enzymes (Pickering & McCabe, 2014). All side effects resolved following the termination of infusions.