For someone living with complex regional pain syndrome (CRPS), seemingly simple activities can become significant obstacles. Wearing a shoe, tolerating light touch or moving an affected arm or leg may trigger intense pain.

As discomfort persists, avoiding movement can feel necessary, yet inactivity can contribute to stiffness, weakness and further loss of function. Part of what makes CRPS so challenging is that the problem may extend beyond the original site of an injury. Changes can occur within affected tissues as well as the nervous system, creating a complex pain cycle that may be difficult to interrupt.

“CRPS is a multi-system disorder,” says Kevin Kane, M.D., a board-certified anesthesiologist and medical director of Ketamine Milwaukee, Edelica Health and Sana Medical Clinics, in Milwaukee. For some patients, he believes that addressing multiple components of that cycle rather than pain alone may offer another path forward.

When the Nervous System Turns Up the Volume

Normally, pain serves an important purpose, alerting the brain to injury or danger. With CRPS, however, pain signaling can become amplified. The brain and spinal cord may become increasingly responsive to sensory input, a phenomenon known as central sensitization.

As a result, a stimulus that would ordinarily cause little or no discomfort can become painful. This may manifest as allodynia, in which something as gentle as clothing or light touch hurts, or hyperalgesia, an exaggerated response to a painful stimulus.

At the same time, changes may be occurring in the affected limb, including inflammation, impaired circulation, stiffness and tissue dysfunction. Together, peripheral pain signals and an increasingly sensitized nervous system may help perpetuate the cycle.

Understanding these different contributors is one reason a multimodal approach to CRPS treatment may be considered.

Quieting an Overactive Pain Response

Intravenous ketamine is one therapy used in some cases of treatment-resistant CRPS. Ketamine blocks N-methyl-D-aspartate (NMDA) receptors, which play a role in pain signaling and central sensitization.

Research has demonstrated reductions in pain among some CRPS patients receiving ketamine, although responses and duration of relief vary.

Kane describes the treatment as a way of “turning down the amplifier” within an overly reactive nervous system. Reducing sensitivity may also create an important opportunity: allowing a person to tolerate touch and movement that previously felt unbearable.

Looking Beyond the Nervous System

If ketamine targets central pain processing, focused Extracorporeal Shockwave Therapy (ESWT) approaches the problem from another direction.

ESWT delivers acoustic waves to targeted tissues and is used for a variety of musculoskeletal conditions. Research suggests that it can influence inflammatory processes, circulation and tissue remodeling. Limited research has also explored its potential application for CRPS.

The theory behind combining these therapies is relatively straightforward: reduce amplification of pain within the central nervous system while also addressing potential sources of painful input from affected tissues.

Research specifically evaluating ketamine and ESWT together for CRPS remains limited, however, and larger clinical trials are needed to determine whether the combination provides benefits beyond either treatment independently.

Reducing Pain and Getting Back to Fully Living

Reducing pain is important, but for many people with CRPS, the larger goal is getting back to the things they love.

Pain can lead to fear of movement, known as kinesiophobia. Over time, avoiding an affected limb may contribute to weakness, stiffness and loss of mobility, potentially making recovery even more difficult.

This is where a reduction in pain may become particularly meaningful. When sensitivity decreases and movement becomes more tolerable, patients may be better able to participate in guided physical rehabilitation.

Kane recalls one patient whose reported pain decreased from seven out of 10 to four after ESWT was added to her ketamine treatment. Perhaps more meaningful than the number, he says, was a functional milestone: she could comfortably wear shoes again.

While one person’s experience cannot predict another’s outcome, the example illustrates an important shift in the conversation about chronic pain. Success does not have to be measured by pain scores alone. Walking, sleeping, exercising, working or simply wearing normal clothing may represent meaningful progress.

Asking Better Questions About Pain

There is no single solution for CRPS. Patients considering ketamine, ESWT or other therapies should discuss the available evidence, potential risks, contraindications and alternatives with qualified health care professionals.

It’s helpful to ask the question: What factors could be perpetuating the pain?

For some patients, looking at nervous system sensitization, tissue health, mobility and rehabilitation together may reveal opportunities that treating one component alone does not.

CRPS is complicated, but understanding that complexity can be empowering. The objective is not simply to silence pain. It is to create opportunities for movement, function and, ultimately, a fuller return to daily life.

Dr. Kevin Kane, M.D., is a board-certified anesthesiologist, and is founder and medical director at Ketamine Milwaukee, Edelica Health, and Sana Medical Clinics in Milwaukee, Wisconsin. To book an appointment, call 414-206-1606 a or visit EdelicaHealth.com.