Dorsal Root Ganglion Neurostimulation for Treating Complex Regional Pain Syndrome Types I and II

Proprietary names: Axium™ Neurostimulation System, Axium Implantable Neurostimulator (model MN10200), Axium Trial Neurostimulator (model MN10100), Axium Clinician Programmer (MN10700), Axium Patient Programmer (MN10600-2), SlimTip Leads (models MN10350-50A, -90A; MN10450-50A, -90A), Proclaim™ Elite DRG Neurostimulation System, Proclaim DRG Implantable Pulse Generator (model 3664), Proclaim Clinician Programmer App (model 3874), Proclaim Patient Programmer App (model 3875).

Generic names: dorsal root ganglion (DRG) stimulation.

Complex regional pain syndrome (CRPS) is a condition that involves pain, inflammation, and autonomic dysregulation occurring in the absence of noxious stimuli and often affecting one or more limbs.1-3 Patients may experience exaggerated pain in response to harmful stimuli (hyperalgia) and pain in response to harmless stimuli (allodynia).3,4 Inflammation may cause affected limbs to appear swollen, red, and warm. Alternatively, limbs may appear cold, moist, and discolored as a result of autonomic dysregulation of vasoconstriction and sweating.2 Autonomic dysregulation may also affect nail, hair, and bone growth, resulting in atrophy.2 CRPS has a variable course. Symptoms may change and spread locally or to other limbs. CRPS may resolve spontaneously after weeks or months, but about 15% of patients experience long-term symptoms that may cause permanent disability.2,3,5

Acute nerve injury plays a role in CRPS onset; however, the mechanism leading from injury to chronic nerve sensitization is not well understood.1 Evidence of nerve damage is present in some cases, classified as CRPS type II (CRPS-II). Patients with CRPS type I (CRPS-I) have no obvious neuropathy but typically report onset after surgery, trauma, or prolonged immobilization.2,4,5 Myocardial infarction and polymyalgia rheumatica may also precipitate CRPS.2,6-8 Other risk factors include smoking, female gender, Caucasian race, and age between 40 and 60.3,5

Clinicians diagnose CRPS based on signs and symptoms.2 The International Association for the Study of Pain defines CRPS based on four sign and symptom categories: sensory, vasomotor, sudomotor/edema, and motor/trophic.2,3,6,9,10 Symptoms in at least three categories and signs in two are diagnostic in the absence of other potential etiologies.

Because of the variable nature of CRPS, clinicians tailor treatment to meet each patient's needs.2,3 First-line treatments include physical therapy and pharmacotherapy. Physical therapy aims to restore limb function through sensory and motor training techniques.3 Pharmacotherapy aims to relieve CRPS symptoms and may consist of anti-inflammatory, analgesic, and anesthetic medication.2,3,11,12 Some experts also propose that antioxidants, cannabinoids, capsaicin, calcitonin, bisphosphonates, and immunoglobulins may be useful for treating CRPS.2,6,12

Several invasive options are available for patients who do not experience satisfactory pain relief with first-line pharmacotherapy.1,6,11,13 Physicians may inject anesthetics into sympathetic ganglions or in the epidural space around spinal nerve roots to achieve temporary relief.2,3,6,11,14,15 Some patients may benefit from an implanted pump that continuously delivers drugs to the cerebrospinal fluid.16,17 An alternative approach aims to block pain nerve signals by using electric pulses to continuously stimulate nerve centers, usually the spinal cord.1,12,13,18,19 Spinal cord stimulation (SCS) involves surgery to place up to 20 electrodes on the target region and connect them to a subcutaneous stimulator.1,19 Patients typically undergo psychological evaluation and trial with a temporary device to become eligible for the procedure.18-20

Despite the number of treatment options, experts consider CRPS management to be challenging because treatments often fail to provide sufficient pain relief, and some involve significant risks, such as drug side effects and spinal surgery complications.2,3 In addition, experts do not agree on evidence-based treatment guidelines, citing a lack of quality studies. Thus, treatment decisions are largely based on clinician experience and opinion, which may result in treatment delays and increased risk of disability.2,3

Few data are available on the incidence and prevalence of CRPS. As of 2017, only two major epidemiologic studies of CRPS have been conducted in the United States and The Netherlands.2,21-23

A 1989–1999 epidemiologic survey that included over 100,000 patients in Olmsted County, Minnesota, USA, found an incidence rate of 5.5/100,000 person-years for CSRP-I and a prevalence rate of 20.6/100,000.5,22 Patients were more frequently female by a 4:1 ratio. In the same study, CSRP-II had an incidence of 0.8/100,000 person-years and a prevalence rate of 4.2/100,000. The sex ratio among patients...