What is CRPS? Understanding Complex Regional Pain Syndrome

Complex Regional Pain Syndrome (CRPS) is a chronic pain condition that can develop after an injury, surgery, stroke, or heart attack. It’s characterized by persistent pain and inflammation, often disproportionate to the initial injury. While CRPS can affect any part of the body, it most commonly impacts the arms, legs, hands, or feet. The onset of CRPS is typically triggered by trauma or injury to the affected limb or body area.

CRPS is categorized into subtypes. CRPS-1, also known as Reflex Sympathetic Dystrophy (RSD), arises after an illness or injury without identifiable nerve damage. CRPS-2, previously called causalgia, is linked to specific nerve damage. CRPS-1 is the more prevalent form. Furthermore, CRPS can be described based on skin temperature sensations, categorized as Warm CRPS, typically observed in the early stages, and Cold CRPS, which is more common in ongoing or chronic cases.

Individuals with CRPS experience pain that is far more intense than expected, even in the absence of ongoing visible injury. Additional symptoms include changes in skin color, temperature fluctuations, and swelling in the affected limb, usually below the site of the initial injury. The symptoms of CRPS are dynamic and can evolve over time, with variations in pain type, skin color, and temperature changes being common.

CRPS can be classified as acute (short-term) or chronic (lasting beyond three months). Early research suggested favorable outcomes, with most patients recovering within a year and experiencing minimal long-term pain. However, more recent studies indicate that while symptoms and disability tend to improve over time, many individuals continue to experience some degree of pain even after a year. Severe or prolonged CRPS can be significantly debilitating, potentially hindering a person’s ability to work or engage in everyday activities. The severity of CRPS is influenced not only by the initial injury but also by the individual’s overall health. Younger individuals, children, and teenagers tend to have better recovery prospects, as do healthy older adults with good circulation and nutrition. Factors like smoking and diabetes can complicate recovery, as can prior chemotherapy treatments. Smoking cessation and effective diabetes management can improve the chances of recovery from CRPS.

Symptoms of Complex Regional Pain Syndrome

CRPS symptoms are highly variable, and individuals may not experience all possible symptoms. The pain associated with CRPS can be constant, intermittent, or exacerbated by touch. As recovery progresses, CRPS symptoms typically diminish.

• Spontaneous or Activity-Related Pain: This pain can be persistent or fluctuate with activity levels. Patients often describe it as burning, pins and needles sensations, or a squeezing feeling in the affected limb. Over time, the pain may spread beyond the initial site, encompassing much or all of the arm or leg. In rare instances, “mirror pain” can occur in the corresponding location on the opposite limb, potentially indicating spinal cord neuron involvement. Mirror pain is generally less severe and resolves as the primary injured nerves heal.

• Exaggerated Pain Response (Allodynia and Hyperalgesia): Individuals with CRPS may exhibit heightened sensitivity in the affected area, known as allodynia, where even light touch becomes painful. Using the affected limb can be intensely painful. Hyperalgesia refers to severe or prolonged pain after a mildly painful stimulus, such as a pinprick.

• Skin Temperature and Color Changes: The affected arm or leg may feel warmer or cooler compared to the unaffected limb. Skin color changes are also common, with the skin appearing blotchy, blue, purple, gray, pale, or red, reflecting alterations in blood flow.

• Skin Texture Changes: Chronic CRPS can lead to changes in skin texture due to insufficient oxygen and nutrient supply to the affected limb. The skin may become shiny and thin or, conversely, thick and scaly. Avoiding contact with painful skin, such as washing, can also contribute to these changes.

• Sweating and Nail/Hair Growth Abnormalities: Hair and nail growth on the affected limb may become accelerated or stunted. Abnormal sweating patterns, ranging from profuse sweating to a lack of sweating, can also occur. These functions are regulated by nerves and influenced by blood flow.

• Joint Stiffness: Pain avoidance may lead to reduced movement of the affected limb, resulting in tendon and ligament stiffness and decreased flexibility. This stiffness can further restrict movement and function. Tight ligaments or tendons can also compress or irritate nerves, potentially worsening CRPS symptoms.

• Bone Changes: CRPS is often associated with bone thinning and remodeling, possibly affecting bone marrow. In rare cases, bones in CRPS-affected limbs may become rough or enlarged, for example, after a poorly healed fracture or due to bone cysts. These bone abnormalities can irritate surrounding tissues and nerves, potentially initiating or prolonging CRPS. These changes are often detectable on X-rays or other imaging scans, aiding in pinpointing nerve damage and guiding treatment strategies.

• Muscle Weakness and Movement Disorders: Reduced movement in the affected limb, even without apparent nerve damage controlling movement, is common in CRPS. This can result in muscle weakness due to disuse. In rare cases, abnormal movements such as fixed postures (dystonia), tremors, or jerks may occur, suggesting potential spread of nerve damage to the spinal cord and brain. Muscle strength and movement issues typically resolve as CRPS improves, but some individuals may require surgery to lengthen tendons and restore normal function.

An arm and hand visibly affected by Complex Regional Pain Syndrome (CRPS), demonstrating skin color changes and noticeable swelling.

Who is More Likely to Develop Complex Regional Pain Syndrome?

CRPS is more prevalent in women than men and can occur across all age groups, with the highest incidence around age 40. It is less common in older adults and young children.

The cause of CRPS may be apparent, such as a fracture, or less clear in other cases. The reasons why some individuals develop CRPS after trauma while others do not remain unclear. Several theories attempt to explain how trauma or injury can lead to chronic pain syndromes, including inflammation, nerve damage, and disruptions in nerve signal transmission to the brain.

Common triggers for CRPS include:

• Fractures: Wrist fractures are particularly common triggers. Nerves can be damaged by bone displacement, splintering, or pressure from tight casts. Overly tight or painful casts should be promptly removed and replaced to prevent complications.

• Surgery: Surgical procedures can cause nerve damage through incisions, surgical tools used to retract tissues, sutures, and post-surgical scarring. While nerve damage can sometimes be repaired during surgery, CRPS can still develop even after successful surgeries.

• Sprains and Strains: Connective tissue injuries, such as ankle sprains, can lead to CRPS, even if the injury initially appears minor.

• Burns and Cuts: Burns and cuts can damage underlying nerves. Rarely, cuts or needle sticks can pierce superficial sensory nerves, leading to CRPS.

• Immobilization in a Cast: Casts, used for fracture immobilization, prevent limb use and sensory input (touch, temperature). After cast removal, neurons require time to readjust to normal signaling.

• Nerve Injury: CRPS-2 is directly linked to specific nerve trauma. Some nerve injuries may necessitate surgical repair.

Risk Factors for CRPS

Risk factors are conditions or behaviors associated with an increased likelihood of developing a disease. While having a risk factor doesn’t guarantee disease development, and lacking risk factors doesn’t ensure immunity, certain factors are associated with higher CRPS risk after injury.

Individuals potentially at higher risk include women and those with severe trauma, lower limb injuries (especially foot injuries), or work-related injuries in physically demanding occupations. Experiencing disproportionately severe pain after injury or sensory changes like allodynia also increases risk. Lifestyle and health factors such as smoking, poor circulation, diabetes, autoimmune disorders, and pre-existing nerve damage may also elevate CRPS risk.

Genetics may also play a role in CRPS susceptibility. Family members of CRPS patients might have a higher predisposition to developing CRPS at a younger age. Research is ongoing to identify specific genes involved in CRPS development.

Diagnosis and Treatment of Complex Regional Pain Syndrome

Diagnosing CRPS

CRPS diagnosis relies on clinical evaluation, as no single definitive test exists. A recent injury or surgery can provide diagnostic clues. Early consideration of CRPS is essential in individuals with new-onset limb pain, even without known trauma, to facilitate timely treatment initiation. Prompt evaluation by a healthcare professional is crucial.

Diagnostic approaches include:

• Detailed Clinical Examination: Examination by specialists like neurologists, orthopedists, or plastic surgeons familiar with pain syndromes.
• Budapest Criteria: These criteria, based on reported symptoms and observed signs (allodynia, hyperalgesia, temperature/skin color changes, sweating/swelling changes, reduced mobility), are a valuable diagnostic tool.
• Nerve Conduction Studies: Useful for detecting nerve injuries associated with CRPS-2 but typically normal in CRPS-1.
• Imaging (Ultrasound/MRI): Can reveal nerve and tissue damage. MRI can detect bone and bone marrow abnormalities, aiding in localizing CRPS. Ultrasound can show localized tissue damage.
• Triple-Phase Bone Scans: May reveal bone changes associated with CRPS, assisting in confirming diagnosis in some cases.

Treating CRPS

Early treatment is most effective and may involve several approaches to reduce CRPS onset and severity: resetting casts if pain develops after fracture treatment, aggressive early pain management, and addressing psychological impacts of CRPS. Individuals with prior CRPS history should take preventative measures, such as choosing minimally invasive procedures when possible.

Key treatment strategies include:

• Rehabilitation and Physical Therapy: Considered the cornerstone of CRPS treatment. Movement improves blood flow and reduces symptoms, maintains flexibility, strength, and function. Exercise can help reverse pain-related changes in the spinal cord and brain. Occupational therapy aids in regaining activity and returning to daily tasks.

• Lifestyle Modifications: Elevating affected limbs during rest or sleep helps fluid drainage. Compression stockings or sleeves can reduce swelling, especially when standing.

• Psychotherapy: Severe CRPS can lead to secondary psychological issues like depression, anxiety, and PTSD, which can worsen pain and hinder recovery. Psychological treatment can improve well-being and facilitate engagement in rehabilitation.

• Graded Motor Imagery: This technique uses mental exercises, including imagining movements of painful body parts and mirror therapy (watching the unaffected limb move in a mirror), to “retrain” the brain and reduce pain perception.

• Medications: Various medications can be effective, especially when started early, although none are FDA-approved specifically for CRPS. A doctor may recommend:

  • Acetaminophen for bone and joint pain.
  • NSAIDs (aspirin, ibuprofen, naproxen) for moderate pain and inflammation.
  • Nerve pain medications: nortriptyline, gabapentin, pregabalin, duloxetine.
  • Topical pain relievers: lidocaine ointments/sprays/creams, fentanyl patches (for allodynia).
  • Bisphosphonates (alendronate, pamidronate) to reduce bone changes.
  • Corticosteroids (prednisolone, methylprednisolone) for inflammation/swelling.
  • Botulinum toxin injections for severe cases, muscle relaxation, and restoring limb position.
  • Opioids (oxycodone, morphine, hydrocodone, fentanyl) for severe pain, used cautiously due to potential for dependence and pain sensitization.

• Spinal Cord Stimulation: Electrodes implanted near the spinal cord deliver tingling sensations to block pain signals and restore normal function. Temporary trials assess effectiveness before permanent implantation.

• Other Neural Stimulation: Electrical stimulation near injured nerves, transcranial magnetic stimulation (rTMS), and deep brain stimulation are being explored. Peripheral nerve stimulation devices are also available.

• Spinal Drug Pumps: Implanted devices deliver pain medication directly to the spinal fluid, allowing for lower doses and reduced side effects.

• Ketamine Infusion: In severe, unresponsive cases, low-dose intravenous ketamine may be considered, but it carries risks of psychosis and delusions.

Alternative therapies like acupuncture and chiropractic treatment may provide symptom relief for some individuals, although they do not address the underlying nerve damage.

Outdated and ineffective treatments include sympathetic nerve blocks, surgical sympathectomy, nerve or nerve root cutting, and amputation.

Treating Pediatric CRPS

CRPS-1 is more common in girls around age 12. Causes and diagnosis are similar to adults. Triggers in children often involve mild trauma like ankle sprains. Treatment typically involves intensive physical therapy and cognitive behavioral therapy. Medications and other adult treatments may also be considered. CRPS in children often improves within 6-8 months, but recurrence is possible. Some children may experience persistent pain into adulthood.

Latest Research Updates on Complex Regional Pain Syndrome

The National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH, is a leading funder of CRPS research, investigating pain pathways, neuropathic pain, and the transition to chronic pain. The NIH HEAL Initiative® accelerates research into non-addictive pain treatments. The BRAIN Initiative® focuses on neuromodulation for pain reduction.

NINDS-supported research includes:

• Investigating CRPS development mechanisms using model systems.
• Studying genetic and cellular contributions to acute and chronic CRPS phases.
• Analyzing immune system changes in post-traumatic CRPS through serum and skin biopsies, potentially supporting clinical trials with immunotherapies.
• Studying neuroplasticity in children with CRPS to understand factors contributing to better outcomes and develop effective therapies.
• Evaluating ketamine and dexmedetomidine for pain management in children.
• Assessing transcranial magnetic stimulation for pain and associated symptoms.
• Researching at-home transcranial direct current stimulation devices.
• Examining the sympathetic nervous system’s role in pain and inflammation.
• Analyzing brain data from chronic pain patients to identify biomarkers and understand pain representation in the brain.
• Evaluating pain management strategies for children with CRPS, focusing on reintegration into school and play.
• Investigating the role of gut bacteria in CRPS development and potential therapeutic applications.

Resources for finding CRPS research:

• NIH RePORTER (https://www.projectreporter.nih.gov/)
• PubMed (https://pubmed.ncbi.nlm.nih.gov/)

Learn About Clinical Trials

Clinical trials are crucial for advancing knowledge and improving care for CRPS.

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How to Contribute to CRPS Research

Participating in clinical trials helps researchers understand CRPS better and develop improved treatments. All types of participants are needed. For more information on clinical research, visit NIH Clinical Research Trials and You and Clinicaltrials.gov for CRPS-specific trials.

Resources for More Information on Complex Regional Pain Syndrome

• International Research Foundation for RSD/CRPS (https://www.rsdfoundation.org) Phone: 813-995-5511
• NeuropathyCommons.org (https://neuropathycommons.org)
• Reflex Sympathetic Dystrophy Syndrome Association (RSDSA) (https://rsds.org/) Phone: 203-877-3790 or 877-662-7737