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8 Articles in this Series
AAPM's Advice for Evidence-Based Opioid Prescribing Guidelines
CBT for Chronic Pain and Insomnia Needs More Research
Farewell Opioid Therapy, Hello Mental and Behavioral Health
Ketamine’s Growing Use in Chronic Non-Cancer Pain Management
MR Neurography in CRPS Assessment
Navigating New Opioid Prescribing Requirements: Practical Legal Advice for PCPs & Pain Specialists
TACs: Identifying and Treating the Non-Migrainous Headache
Video: Dr. Aronoff on Shifts in Pain Care

MR Neurography in CRPS Assessment

With presentation by Vivianne Tawfik, MD, PhD

Complex regional pain syndrome (CRPS) affects 50,000 new people in the United States each year, with a two-times higher prevalence among women. Those at the highest risk for developing CRPS include individuals with a history of chronic pain or nerve injury, and those who report an increase in early post-operative pain. Vivianne Tawfik, MD, PhD, assistant professor of anesthesiology at the Stanford University School of Medicine, has studied the disease in both animal models and humans for years, with the goal of better understanding CRPS mechanisms.


Chronic Post-Surgical Pain vs Complex Regional Pain Syndrome

When is acute pain no longer considered acute? What is normal? When does chronic post-surgical pain (CPSP) actually become CRPS, and how do the conditions overlap? These are just a few of the questions Dr. Tawfik has set out to answer and she described some of her recent work at the American Academy of Pain Medicine’s 34th annual meeting in Vancouver, in April 2018.

The heat, redness, swelling, and pain that are commonly experienced after surgery, for example, are also common symptoms of CRPS, she explained. Developing mechanism-based treatments, including monitoring the patient’s pain trajectory, is key to differentiating CRPS from CPSP. Those patients who continue to get worse, not better, are the ones we need to see and treat, she said.

Dr. Tawfik also addressed the fact that potential underlying mechanisms of CRPS may all be at play at different points of the disease, which makes the pathophysiology very complex. The acute/peripheral phase may include warmth and edema, for example, while the chronic/central phase may feature a cool limb and atrophy. She noted a study by Bruehl S et al, in Pain in 2016, which demonstrated these phases and related disease duration.

Disease Modeling

To model the disease-specific pain of CRPS mechanisms, Dr. Tawfik’s team has been studying, among other risk factors, casting and immobilization in animal models. Upon cast removal, they found CPRS signs in mice with fractured versus unfractured tibia to be significant. They also noted glio-transmission, the ability of CNS microglia and astrocytes to release pro-inflammatory mediators, as a significant factor in developing CRPS as well as in other pain pathologies. When neurons are injured in pain states, they can trigger microglial activation. To measure glial activation in vivo, Dr. Tawfik’s team used imaging of PET ligands. PET ligands for TSPO (peripheral benzodiazepine receptor) have been developed to mark glial activation. TSPO PET ligand binding increases over time in the lumbar spinal cord of mice, post fracture. So how does this translate to novel approaches, asked Dr. Tawfik.

The Benefits of Imaging & A Multidisciplinary Nerve Team

To better get at the relationship between possible nerve injury and CRPS, her team at Stanford put together a multidisciplinary “peripheral nerve team.” Patients with post-surgical pain referred to the Stanford pain clinic were evaluated and tested (eg, EMG, MR neurography, pain psychology and physical therapy evaluation, among other diagnostics). Then, a multidisciplinary team reviewed the results to devise a multimodal treatment plan.

The researchers found that MR neurography imaging, in particular, greatly helped the pain physicians. “Pain is subjective and a physical exam is not always helpful in determining the etiology,” explained Dr. Tawfik, plus, there are a lot of possible nerves that may contribute to CRPS signs. MR neurography allows you to “see pain” via the peripheral nerves, she said. While it does require a lot of technical and processional expertise, her clinic has been doing as many as 3 to 5 MR neurography scans per day versus the 1 to 2 they used to do per month. It has changed management approaches and surgical decision-making, she reported (see also Chhabra et al, 2016).

Overall, nerve lesions may lead to symptoms anywhere in the affected limb – so scanning should not be minimized or limited to the affected area, Dr. Tawfik advised. When a spine MRI appears normal but you see peripheral symptoms, such as weakness, in the patient, MR neurography may help to better identify the issue. While clinically informed based science research is ongoing, new approaches in imaging such as this can contribute to the evaluation of a patient’s CRPS or peripheral nerve injury, she concluded.



Tawfik V. Complex Regional Pain Syndrome (CRPS): From the Bench to the Bedside and Back. Presented at the American Academy of Pain Medicine, April 26-29, 2018. Vancouver, British Columbia.


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