Complex Regional Pain Syndrome (CRPS): Symptoms, Causes, and Research Options

A wrist fracture heals. The cast comes off. The bone is fine on the X-ray, the orthopedist signs off, and the arm still burns. Weeks later the hand is swollen, the skin has changed color, and a bedsheet brushing against it is enough to make you flinch.

That pattern has a name. Complex regional pain syndrome, or CRPS, is a chronic pain condition in which pain persists at a level far out of proportion to the injury that triggered it, and often long after that injury has healed. It usually affects one limb: a hand, an arm, a foot, or a leg. It was once called reflex sympathetic dystrophy (RSD) or causalgia, and many people diagnosed years ago still know it by those names.

CRPS is not common, and that is part of the problem. Many people cycle through several providers before anyone names it, and by then months have gone by.

What CRPS Feels Like: The Symptoms

The defining symptom is pain that does not match the injury. People describe it as burning, stinging, throbbing, or tearing, and it is usually constant rather than intermittent. Beyond the pain itself, the National Institute of Neurological Disorders and Stroke describes a cluster of changes in the affected limb:

• Heightened sensitivity. Light touch, clothing, or a change in temperature can trigger severe pain (allodynia), and painful stimuli hurt more than they should (hyperalgesia).

• Skin color and temperature changes. The limb may look blotchy, pale, red, or purple, and may feel noticeably warmer or cooler than the other side.

• Swelling. Edema in the affected hand or foot that may come and go or stay persistent.

• Sweating changes. The area may sweat more or less than the matching limb.

• Skin, hair, and nail changes. Skin can become shiny or thin, and hair and nail growth can speed up or slow down.

• Stiffness and weakness. Reduced range of motion, difficulty using the limb, and in less common cases tremor or dystonia.

Two details matter for recognizing it. First, the changes are usually asymmetric: the comparison that gives it away is the affected limb versus the other one. Second, symptoms can move. Some people notice pain appearing in the matching spot on the opposite limb, sometimes called mirror pain.

What Causes CRPS

In the large majority of cases, CRPS follows a physical trauma to the limb. Common triggers include:

• Fractures, which are the most frequent trigger. In the clinical literature reviewed in StatPearls, fractures account for roughly 44 to 46 percent of cases, with wrist and ankle fractures particularly common.

• Surgery, including routine procedures on the hand, wrist, knee, or foot.

• Sprains and strains.

• Burns, cuts, bruises, or needle injuries.

• Prolonged immobilization, such as an extended period in a cast.

CRPS is also divided into two types. Type 1, historically called reflex sympathetic dystrophy, develops without any documented nerve injury. Type 2, historically called causalgia, follows a confirmed injury to a specific nerve. Type 1 is by far the more common of the two.

What is less well understood is why the same injury produces CRPS in one person and not another. Current research points to a combination of inflammatory response, changes in how the peripheral and central nervous systems process pain signals, and altered blood flow to the limb. Risk appears higher in women than in men, and onset commonly falls in middle age. That question, why some patients develop it and others do not, is exactly the kind of question clinical research exists to answer.

How CRPS Is Diagnosed

There is no blood test, scan, or biopsy that confirms CRPS. It is a clinical diagnosis, made by a physician who examines the limb, takes a careful history, and rules out other explanations.

Most clinicians work from a framework known as the Budapest Criteria, developed under the International Association for the Study of Pain. In simplified form, a diagnosis requires four things:

1. Continuing pain that is disproportionate to the inciting event.

2. At least one reported symptom in three of four categories: sensory, vasomotor (temperature and color), sudomotor/edema (sweating and swelling), and motor/trophic (movement, strength, and skin, hair, and nail changes).

3. At least one sign observed at the time of the exam in two or more of those same four categories.

4. No other diagnosis that better explains the findings.

That last point is why imaging and nerve conduction studies still get ordered. They are not used to prove CRPS. They are used to rule out fractures that did not heal, nerve compression, infection, or vascular problems that could account for the same picture.

The practical takeaway: bring specifics to the appointment. Photograph the limb when it is discolored or swollen. Note which touches trigger pain. Track when symptoms started relative to the injury. Those details are the evidence a clinician actually uses.

Treatment Options Available Today

Standard care for CRPS is multimodal, meaning several approaches used together rather than one drug. As outlined by Cleveland Clinic and NINDS, the current toolkit includes:

• Rehabilitation. Physical and occupational therapy, desensitization exercises, mirror therapy, and graded motor imagery. Keeping the limb moving is central, even when movement is what hurts.

• Medications. Anti-inflammatories, anticonvulsants such as gabapentin, certain antidepressants used for nerve pain, corticosteroids, bisphosphonates, and topical agents.

• Interventional procedures. Sympathetic nerve blocks, spinal cord stimulation, and dorsal root ganglion stimulation.

• Psychological support. Cognitive behavioral therapy and biofeedback, which address the anxiety, sleep disruption, and depression that chronic pain commonly brings with it.

Two things are worth saying plainly. Early treatment is associated with better outcomes, which is why the delay to diagnosis matters so much. And no single therapy works reliably for everyone, which is why CRPS remains an active area of drug development.

Where Clinical Research Fits In

Because no approved treatment resolves CRPS for every patient, clinical trials are a meaningful option rather than a last resort. Research studies are how new approaches are evaluated, and participants get access to investigational treatments alongside close medical monitoring.

Arrow Clinical Trials is currently enrolling adults with CRPS in a research study in Daytona Beach, conducted under Protocol AMBTX-01-301 and sponsored by Ambros Therapeutics. Participants in Arrow studies receive study-related visits and care at no cost, oversight from the clinical research team, and compensation for time and travel.

Eligibility for any study is determined by the protocol, not by a website. The only way to know whether a specific study is a fit is to complete a short pre-screening and speak with the research team. If it is not a fit, they will tell you, and that costs you nothing but a phone call.

If you are living with limb pain that started after an injury or surgery and has outlasted the healing, it is worth finding out. You can review the CRPS study and check eligibility, browse all enrolling studies at Arrow, or call the team at (386) 222-3524.

New to clinical research? Two posts worth reading first: Is a Clinical Trial Safe? Understanding Participant Protections and Informed Consent and How to Qualify for a Paid Clinical Trial.

Frequently Asked Questions

What is complex regional pain syndrome (CRPS)?

CRPS is a chronic pain condition in which pain in a limb is far more severe and lasts far longer than the injury that caused it would explain. It typically affects one arm, hand, leg, or foot, and often includes swelling, skin color and temperature changes, and heightened sensitivity to touch. It was previously known as reflex sympathetic dystrophy (RSD) or causalgia.

What causes CRPS?

Most cases follow a physical trauma to the limb. Fractures are the most common trigger, followed by surgery, sprains, burns, cuts, and prolonged immobilization. Type 1 CRPS develops without a documented nerve injury, while Type 2 follows a confirmed nerve injury. Researchers believe inflammation, changes in nervous system pain processing, and altered blood flow all contribute.

How is CRPS diagnosed?

There is no single test for CRPS. Physicians diagnose it clinically using the Budapest Criteria, which require pain disproportionate to the injury, reported symptoms across at least three of four categories, observed signs in at least two of those categories, and no better alternative explanation. Imaging and nerve studies are used to rule out other conditions.

Is there a cure for CRPS?

There is no single treatment that resolves CRPS in every patient. Care is usually multimodal, combining physical and occupational therapy, medications, interventional procedures such as nerve blocks or spinal cord stimulation, and psychological support. Outcomes tend to be better when treatment begins early, which is why prompt diagnosis matters.

Are there CRPS clinical trials in Daytona Beach, Florida?

Yes. Arrow Clinical Trials in Daytona Beach is enrolling adults with CRPS in a research study under Protocol AMBTX-01-301, sponsored by Ambros Therapeutics. Study-related visits and care are provided at no cost, and participants are compensated for time and travel. Eligibility is determined during pre-screening with the research team.