Background

Pain is nearly universal, contributing substantially to morbidity, mortality, disability, and healthcare system burdens.¹ Acute pain usually lasts for less than 7 days but often extends up to 30 days, and may recur periodically. Although acute pain usually resolves rapidly, in some cases it can persist to become chronic. Chronic pain, defined as pain lasting longer than 3 months^1,2 is a serious public health issue in the United States, affecting approximately 50 million people and resulting in $635 billion in costs.^3,4 Chronic pain substantially impacts physical and mental functioning, reducing productivity and quality of life.

Patients eligible for Medicare due to age or disability are highly impacted by pain. Musculoskeletal conditions such as back pain are the most common Social Security Disability Insurance qualifying diagnosis, accounting for 34 percent of program participants in 2011.⁵ In 2016, approximately 13.6 million Americans 65 years of age or older were estimated to have chronic pain and 5.4 million had high-impact chronic pain.⁴ The prevalence of chronic pain was 27.6 percent among those 65 to 84 years of age and 33.6 percent among those 85 years of age or older (exceeding any other age group). In older adults, management of pain is often complicated by medical comorbidities, polypharmacy, increased susceptibility to treatment harms, and assessment challenges due to impaired cognition, often resulting in untreated or under treatment of pain.^6,7

Opioids, traditionally considered the most potent analgesic, are frequently prescribed for acute or chronic pain, including in older adults and those with disabilities.^5,8,9 Therefore, pain management must be considered within the context of the current opioid crisis (related to both illicit and prescription opioids).¹⁰ Opioid prescribing is highest among patients over 65 years of age, and studies indicate recent increases in hospitals admissions and emergency department visits related to opioid use disorder in this age group.^11–14 Therefore, there is a need to identify effective and safe interventions that could augment or replace opioids for pain treatment in this population.

The key decisional dilemma for pain management in Medicare beneficiaries is providing adequate pain relief, in order to improve quality of life and improve function, while minimizing harms. Given concerns regarding opioids, there is great interest in nonopioid pharmacologic and nonpharmacologic therapies and they have become increasingly accepted as first-line therapies. The 2016 Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain recommends nonopioid therapy as preferred for treatment of chronic pain,^15–17 though opioids remain an option for appropriately selected and monitored patients. In the aging population, the Pain Management Best Practices Inter-Agency Task Force report recommended consideration of a multidisciplinary approach with nonpharmacologic emphasis.¹⁸ Interventional approaches were also specifically highlighted by the Task Force as an important nonpharmacologic option and data indicate that interventional procedures are frequently used in this population (~5 million procedures annually in Medicare fee-for-service).¹⁹

The term “interventional procedure” has been applied to a myriad of procedures, ranging from soft tissue injections to minimally invasive surgeries, but in this report it refers to nonsurgical interventional procedures (i.e., excluding minimally invasive surgical procedures). The Inter-Agency Task Force report suggested that a number of interventional procedures be considered for acute or chronic pain,¹⁸ but did not specifically make recommendations for use of these procedures in Medicare populations, in whom optimal management of pain must consider factors such as medical comorbidities, polypharmacy, presence of disability, falls risk, and cognitive issues.²⁰

Purpose of the Review

The purpose of this systematic review is to evaluate the effectiveness and harms of selected interventional procedures in the Medicare population. The review focuses on procedures that are not currently covered by the Centers for Medicare & Medicaid Services (CMS) but are relevant for and have potential utility for use in the Medicare population, or procedures that are covered by CMS but for which there is important uncertainty or controversy regarding use. The intended audiences for this review are CMS and other stakeholders including clinicians, policymakers, patients, and researchers. This review is part of the Dr. Todd Graham Pain Management Study and is sponsored by CMS. The Dr. Todd Graham Pain Management Study also includes three complementary topic briefs on pain topics in Medicare populations as well as a separate systematic review²¹ on integrated pain management and multidisciplinary multi-modal treatment models.

Scope and Key Question

The draft Key Question and scope were developed by the Evidence-based Practice Center with input from the Agency for Healthcare Research and Quality and CMS, and were revised based on input from a Technical Expert Panel prior to finalization. The interventional therapies were selected based on the following factors: (1) available in the United States but not currently covered by CMS; (2) relevance and potential utility in the Medicare population (i.e., use in Medicare-eligible patients or for pain conditions commonly encountered in this population); and (3) uncertainty or controversy regarding use.

Key Question 1.

What are the effectiveness and harms of selected interventional procedures (vertebral augmentation procedures, cooled or pulsed radiofrequency ablation, intradiscal and facet joint platelet-rich plasma, intradiscal methylene blue, intradiscal ozone, sphenopalatine block, occipital nerve stimulation, piriformis injection, and peripheral nerve stimulation) versus placebo, a sham procedure, or no interventional procedure for Medicare beneficiaries with pain?

1. How do the effectiveness and harms vary according to demographic (age, sex, race/ethnicity), clinical (type of pain, severity of pain, prior treatments, medical and psychiatric co-morbidities), and technical factors (variations in techniques, intensity, frequency, dose, and number of treatments)?

1. Vertebral augmentation procedures (vertebroplasty and kyphoplasty) for vertebral compression fracture. These procedures are performed for vertebral compression fractures, which are common in the Medicare population and often are due to osteoporosis or metastatic disease. Vertebroplasty involves the injection of polymethyl methacrylate (PMMA), commonly known as bone cement, into the collapsed (fractured) vertebral body. In kyphoplasty, injection of PMMA is preceded by insertion and inflation of a balloon into the collapsed vertebral body to restore it. Although vertebral augmentation procedures are covered by CMS, they were selected for inclusion in this review because there is ongoing controversy about their role, due to conflicting trial results.^22,23 The conflicting trial results could be due to use of a sham intervention (mimicking the vertebral augmentation procedure, without injecting PMMA, in order to blind participants to the treatment received) versus a usual care (open-label) control. Other factors that could impact trial results include the fracture age, presence of imaging findings indicating bone marrow edema in the fracture, the volume of PMMA used, and others.
2. Variations on radiofrequency ablation (cooled radiofrequency ablation for degenerative low back or hip pain and pulsed radiofrequency ablation for degenerative low back pain). Conventional radiofrequency ablation involves the application of continuous high frequency electrical current to ablate nerve tissue thought to be the cause of pain. Evidence indicates that conventional radiofrequency for low back and hip pain may be associated with improved short-term pain and function,^24,25 and it is currently covered by CMS for these conditions as an option for patients with persistent symptoms who do not respond to standard treatments. Cooled and pulsed radiofrequency have been proposed as potential alternatives to conventional radiofrequency. Like conventional radiofrequency ablation, the cooled radiofrequency procedure involves the application of high frequency electrical current. It differs from conventional radiofrequency ablation by using a larger, “cooled” (relative to conventional radiofrequency; heat is still generated) radiofrequency probe, potentially allowing for more targeted, larger and more effective lesions.^26,27 The Coolief™ cooled radiofrequency ablation probe was approved by the U.S. Food and Drug Administration (FDA) for treatment of knee pain. However, it has also been proposed as an alternative to conventional radiofrequency ablation for other indications, including degenerative back and hip pain. Pulsed radiofrequency differs from conventional radiofrequency by delivering a smaller current in brief bursts. Unlike conventional radiofrequency, it is not intended to destroy nerve tissue; rather, it is thought to reduce pain through neuromodulatory effects.²⁸
3. Intradiscal and facet joint platelet-rich plasma for presumed discogenic back pain or presumed facet joint pain. This procedure involves the injection of autologous platelet-rich plasma, which is rich in growth factors, into the intervertebral disc for low back pain of presumed discogenic origin²⁹ or into the lumbar facet joint for low back pain of presumed facet joint origin.³⁰ Platelet-rich plasma is thought to promote endogenous healing processes, though the exact mechanism of action is not well understood.
4. Intradiscal stem cells for presumed discogenic back pain. This procedure involves the injection of stem cells, which have potential regenerative potential, into degenerative intervertebral discs for low back pain of presumed discogenic origin.³¹ Like platelet-rich plasma, stem cells are thought to promote healing.
5. Intradiscal methylene blue for presumed discogenic back pain. This procedure involves the injection of methylene blue, a dye that may prevent fibrosis or ablate sensory endings, into the intervertebral disc for low back pain of presumed discogenic origin.³² However, the mechanism of action is not well understood.
6. Intradiscal ozone injection for radicular or nonradicular back pain. This procedure involves the injection of ozone, a gas with potential anti-inflammatory or other effects, into the intervertebral disc for radicular low back pain due to herniated disk or nonradicular low back pain of presumed discogenic origin.³² Ozone may have nucleolytic effects on the intervertebral disc, reducing the size of the herniated disc and relieving pressure on compressed nerve roots, or reduce pain related to discogenic pain through anti-inflammatory effects.³³
7. Sphenopalatine block for trigeminal neuralgia or headache. This procedure is performed for trigeminal neuralgia, migraine headaches, cluster headaches, and other headache syndrome.³⁴ It involves injection of the sphenopalatine ganglion with a local anesthetic; the FDA has approved three devices for this procedure (SphenoCath® [Dolor Technologies, Scottsdale, AZ], Allevio SPG Nerve Block catheter [Medical Components, Inc., Schwenksville, PA], and Tx360® Nasal Injector [Tian Medical, LLC, Libertyville, IL]). The most common method for approaching the sphenopalatine ganglion is via the transnasal approach.
8. Occipital nerve stimulator for headache. This procedure is performed for various headache disorders. Similar to spinal cord stimulation, it involves electrical stimulation of the occipital nerve through use of subcutaneously placed electrodes, which is thought to result in neuromodulation of pain via the gate control pathway.³⁵ Typically, a successful trial of stimulation is performed before permanent electrodes and a generator are implanted.
9. Piriformis injection for piriformis syndrome. Piriformis syndrome results from compression of the sciatic nerve by the piriformis muscle.^36,37 The injection may be performed using corticosteroids (for anti-inflammatory effects), local anesthetics (to decrease muscle spasm), and/or botulinum toxin (also to decrease muscle spasm).
10. Peripheral nerve stimulation for ulnar, median, and radial neuropathy. This procedure involves stimulation of peripheral nerves using a mild electrical current, in patients with chronic neuropathic pain such as upper extremity neuropathies.³⁸ Like occipital nerve stimulation, peripheral nerve stimulation involves the subcutaneous placement of electrodes at the target nerves and is thought to have neuromodulatory effects. Successful trial stimulation is typically required prior to permanent placement.

This review did not address minimally invasive surgical procedures, or orthopedic procedures such as intra-articular or soft tissue corticosteroid, hyaluronic acid, or soft tissue or nonspinal intra-articular platelet-rich plasma injections. The review also did not address soft tissue injections with local anesthetic, corticosteroid, and/or other medications (e.g., botulinum toxin) that are commonly performed in primary care settings and do not require specialized training or expertise. With the exception of vertebral augmentation procedures, it also does not address interventional procedures conducted in the Medicare population that are covered by CMS, are recommended in clinical practice guidelines, and/or have been addressed in other recent and comprehensive systematic reviews (e.g., epidural steroid injection, perioperative peripheral and central regional anesthetic techniques, and spinal cord stimulation).^32,39–44