Noninvasive Nonpharmacological Treatment for Chronic Pain:
A Systematic Review Update
(April 16, 2020).

Andrea C. Skelly, Ph.D., M.P.H., Roger Chou, M.D., Joseph R. Dettori, Ph.D., M.P.H., M.P.T.,
Judith A. Turner, Ph.D., et al.

Rockville (MD): Agency for Healthcare Research and Quality (US); 2020 (Apr)

This section was compiled by Frank M. Painter, D.C.
Send all comments or additions to:



Nature and Burden of Chronic Pain

Chronic pain substantially impacts physical and mental functioning, productivity, quality of life, and family relationships; it is the leading cause of disability; and is often refractory to treatment.1,2 A monumental public health challenge, chronic pain affects millions of adults in the United States, with a conservative annual cost in personal and health system expenditures estimated at $560 billion to $635 billion.3 The Centers for Disease Control and Prevention (CDC) estimated that 1 in 5 adults in the United States experienced chronic pain in 2016, with 8 percent reporting high-impact chronic pain that limited life or work activities daily or most days in the previous 6 months.4,5

Pain is usually regarded as chronic when it lasts or recurs for more than 3 to 6 months, however definitions vary.6,7 For purposes of this report, chronic pain is defined as pain lasting 3 months or longer, or persisting past the normal time for tissue healing.3,8 Nervous system changes that occur with chronic pain, combined with its psychological and cognitive impacts, have led to conceptualization of some types of chronic pain as a distinct disease entity.3 Chronic pain is multifaceted and influenced by multiple factors (e.g., genetic, central nervous system, psychological, and environmental factors) and complex interactions of factors, making pain assessment and management a challenge. A number of characteristics influence the development of and response to chronic pain, including sex, age, presence of comorbidities, and psychosocial factors. For example, women report chronic pain more frequently than do men, are at higher risk for some conditions such as fibromyalgia,3 and may respond to treatment differently than men. Older adults are more likely to have comorbidities and are more susceptible to polypharmacy, impacting choices and consequences of therapies. Pain is greatly influenced by psychosocial factors, which may predict who will develop chronic disabling pain, as well as who will respond to various treatments.

Management of Chronic Pain

Many pharmacological and nonpharmacological treatments are available for management of chronic pain and include a variety of noninvasive as well as surgical and interventional procedures. The National Pain Strategy Task Force report recommends that pain management be integrated, multimodal, interdisciplinary, evidence-based, and tailored to individual patient needs.9 In addition to addressing biological factors when known, optimal management of chronic pain must also address psychosocial contributors to pain, while taking into account individual susceptibility and treatment responses. Self-care is also an important part of chronic pain management.

Opioids have been used in the treatment of chronic pain. In the past 20 years, evidence shows only modest short-term benefits of these drugs.1012 Lack of evidence on long-term effectiveness13 and safety concerns14 have been noted in the literature. The recent evidence-based CDC guidelines on opioid use for chronic pain,15 which include a recommendation on the preferred use of nonopioid treatment over opioid therapy, has prompted additional primary research on alternative methods of managing chronic pain.

Other pharmacological treatments for chronic pain include nonsteroidal anti-inflammatory drugs, acetaminophen, muscle relaxants, antiseizure medications, antidepressants, and corticosteroids, used alone or in combination with each other or with opioids. Each has potential side effects and contraindications.

Nonpharmacological treatments for chronic pain examined in this review include exercise, mind-body practices, psychological therapies, multidisciplinary rehabilitation, mindfulness practices, manual therapies, physical modalities, and acupuncture.

      Rationale for This Review Update

This systematic review updates our 2018 review. Our 2018 review16 provided some support for clinical strategies and policies that focus on nonpharmacological therapies for chronic pain that have evidence of sustained effectiveness after the completion of therapy but numerous evidence gaps were identified. Studies published subsequent to our previous review may provide additional evidence to address some of these gaps. This review provides the most current evidence assessment and synthesis to inform clinical practice and health policy.

The review is intended to address some of the needs described in the National Pain Strategy Task Force9 and Institute of Medicine3 reports and others for evidence to inform guidelines and healthcare policy (including reimbursement policy) related to use of noninvasive nonpharmacological treatments. Both the Institute of Medicine report and the National Pain Strategy Task Force report describe the need for evidence-based strategies for the treatment of chronic pain that address the biopsychosocial nature of this disease, including nonpharmacological treatment. These initiatives, and others, speak to the importance of understanding current evidence on noninvasive nonpharmacological treatment of chronic pain.

Many trials have examined the impact of interventions on outcomes during or immediately after the course of treatment. A number of them are associated with improved function and reduced pain. However, given the persistence of chronic pain, understanding whether the benefits are durable would be very helpful for informing selection of therapies. This review also aims to provide additional insights into research gaps related to use of noninvasive nonpharmacological alternatives for treating chronic pain. Musculoskeletal pain, particularly related to joints and the back, is the most common single type of chronic pain.3,17 This systematic review thus focuses on five of the most common causes of musculoskeletal pain: chronic low back pain, chronic neck pain, osteoarthritis (OA), fibromyalgia, and chronic tension headache.

      Scope and Key Questions

This Comparative Effectiveness Review focused on noninvasive nonpharmacological therapy for five common chronic pain conditions: low back pain, neck pain, OA, fibromyalgia, and headache. Individual pain management strategies considered in the review include exercise (including aspects of physical therapy), mind-body practices (yoga, tai chi, qigong), psychological therapies (cognitive-behavioral therapy, biofeedback, relaxation techniques, acceptance, and commitment therapy), multidisciplinary rehabilitation (including functional restoration training), mindfulness practices (meditation, mindfulness-based stress reduction practices), manual therapies (e.g., musculoskeletal manipulation), physical modalities (traction, ultrasound, transcutaneous electrical nerve stimulation, low-level laser therapy, interferential therapy, superficial heat or cold, bracing for knee, back or neck, electro-muscular stimulation, and magnets), and acupuncture.

We focused on single active interventions and comparators over the long term. The Key Questions, PICOTS (populations, interventions, comparators, outcomes, timing, settings, and study designs), and analytic framework that guided this review are provided below.

      Key Questions

Key Question 1.   Adults with chronic low back pain

Key Question 2.   Adults with chronic neck pain

Key Question 3.   Adults with osteoarthritis-related pain (knee, hip, hand)

Key Question 4.   Adults with fibromyalgia

Key Question 5.   Adults with chronic tension headache

Key Question 6.   Do estimates of benefits and harms differ by age, sex, presence of comorbidities (e.g., emotional or mood disorders), or degree of nociplasticity/central sensitization?

Key Questions 15 incorporate the following subquestions:

  1. What are the benefits and harms of noninvasive nonpharmacological therapies compared with sham treatment, no treatment, waitlist, attention control, or usual care?

  2. What are the benefits and harms of noninvasive nonpharmacological therapies compared with pharmacological therapy (e.g., opioids, nonsteroidal anti-inflammatory drugs, acetaminophen, antiseizure medications, antidepressants, topical agents, medical cannabis, and muscle relaxants)?

  3. What are the benefits and harms of noninvasive nonpharmacological therapies compared with exercise or, for headache, biofeedback?

The three-part format for Key Questions 15 reflects the following research concepts:

  • Part a answers the question of whether the various interventions work overall compared with sham, waitlist control, attention control, no treatment, or usual care. For this review, usual care was defined as care that might be provided or recommended by a primary care provider.

  • Part b answers the question of whether the various interventions work compared with pharmacological alternatives.

  • Part c answers the question of how outcomes for individual interventions (e.g., acupuncture) compare with a common comparator. Exercise is the most frequent comparison in the literature for many chronic pain conditions, so it provides a common comparator for analysis. It is also recommended in most guidelines for conditions including low back pain, neck pain, fibromyalgia, and osteoarthritis and is widely available. Exercise served as common comparator for these conditions. For chronic headache, biofeedback provided a common comparator for analysis.

      Analytic Framework

Figure 1

The analytic framework (Figure 1) illustrates the population, interventions, outcomes, and adverse effects that guided the literature search and synthesis.

Return to:   Noninvasive Nonpharmacological Treatment (2020)

                       © 19952021 ~ The Chiropractic Resource Organization ~ All Rights Reserved