Introduction to CRPS
Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder that can develop after an injury, surgery, or even minor trauma. The pain is typically out of proportion to the original injury and is accompanied by other symptoms such as burning, sensitivity to touch (allodynia), changes in skin color or temperature, swelling, and stiffness. Over time, CRPS can also cause muscle weakness, loss of coordination, and significant functional disability.
Prevalence and Burden
CRPS is uncommon, with an incidence of roughly 5 to 25 cases per 100,000 people per year. However, the impact for those who suffer from symptoms of CRPS can be very profound. CRPS often results in reduced mobility, psychological distress, and high rates of work-related disability. Many people describe it as life-altering, and even with treatment, some remain very limited in their daily activities.
Current Treatments and Their Limits
The standard of care for CRPS involves a multimodal approach. This typically includes physical and occupational therapy, neuropathic pain medications (such as gabapentin or duloxetine), nonsteroidal anti-inflammatory drugs, sympathetic nerve blocks, psychological therapies, and other pain medications. In more severe or refractory cases, options like spinal cord or dorsal root ganglion stimulation are considered.
Despite these interventions, treatment failure is common. Reviews suggest that up to 30–40% of patients continue to experience disabling pain and functional impairment even after trying multiple therapies. For this subset, alternatives like ketamine have emerged as an area of interest.
How Ketamine Works as a Treatment for CRPS Pain
Ketamine acts on many different receptors in the body, including the NMDA receptors in the nervous system. NMDA receptor overactivity is thought to play a key role in central sensitization, a process where the nervous system becomes hypersensitive and amplifies pain signals. By dampening this pathway, ketamine may help “reset” abnormal pain signaling. Beyond NMDA antagonism, ketamine may also reduce inflammation in the nervous system, enhance descending inhibitory pathways, and encourage synaptic plasticity, mechanisms that could help break the vicious cycle of CRPS.
What the Research Shows
Most of the research on ketamine for CRPS has focused on intravenous (IV) infusions. A landmark randomized controlled trial demonstrated that subanesthetic ketamine infusions could significantly reduce pain in CRPS patients, with some experiencing relief lasting weeks to months. Other open-label and controlled studies have echoed these results, though improvements in function have been less consistent. Systematic reviews conclude that ketamine shows promise, but protocols vary widely in terms of dosage and duration, and high-quality studies remain limited.
Intramuscular (IM) Ketamine: A Gap in the Evidence
While IV ketamine has the strongest evidence base, there is a striking lack of research on intramuscular (IM) ketamine for CRPS. To date, there are no large trials specifically examining IM protocols in this population. Some clinicians use IM dosing in practice, but this is guided more by experience than by published evidence. For patients exploring this option, it’s important to recognize the absence of strong data and weigh risks and benefits carefully.
At Horizon Healing, we have had success in implementing an intramuscular ketamine protocol for patients suffering from CRPS that emphasizes the transformative potential of ketamine.
