Inna Belfer, Wen Chen, Emmeline Edwards, David Shurtleff, & Helene Langevin National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH), Bethesda, Maryland, USA Complementary health approaches include a broad range of practices, interventions, and natural products that are not typically part of conventional medical care (Table 28.1). The term complementary refers to the use of these approaches together with conventional therapies and is increasingly preferred to the term alternative, which denotes usage as a substitute for standard care [1]. The term integrative health care refers to conventional and complementary approaches used together in a coordinated way. Integrative health also emphasizes care of the whole person that aims to improve health in multiple interconnected domains: social, psychological, and physical, including multiple organs and systems (Figure 28.1) [1]. Painful conditions are the most common reasons why American adults use complementary health approaches [2]. About 40 million American adults experience severe pain in any given year [3], and they spend more than $14 billion out‐of‐pocket on complementary approaches to manage their pain [4]. The International Association for the Study of Pain recently revised its definition of pain to “. . . an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage [5].” This new definition acknowledges that pain and nociception are different phenomena and that pain cannot be inferred solely from activity in sensory neurons. Many complementary and integrative health approaches are multimodal in nature and may contribute to pain relief by impacting several pain‐processing structures simultaneously, and they address the cognitive, emotional, and physical complexities associated with pain. Chronic pain management is often refractory to conventional medical approaches, and standard pharmacologic approaches have substantial drawbacks. Health care guidelines of the American College of Physicians and other professional organizations recognize the value of certain complementary approaches as adjuncts to pharmacologic management. Research has shown that some complementary health modalities may reduce some pain conditions, including acupuncture, spinal manipulation, and yoga for chronic back pain and tai chi for fibromyalgia [8, 9, 10, 11, 12] Although complementary approaches vary greatly, it is useful to classify them by their primary therapeutic input, which may be dietary (e.g. special diets, herbs), psychological (e.g. meditation), physical (e.g. massage, acupuncture) or the combination of psychological and physical (e.g. yoga). Table 28.1 Glossary of Complementary Health Approaches Used for Managing Pain Natural products, including plants and animal products, have been used for millennia for pain relief, and have been the source of many drugs (e.g. salicylates, opioids). Recent research to identify new sources of analgesics based on natural products also has yielded valuable tools for probing the molecular features of pain pathways. Coupled with human genetics, preclinical animal models, and clinical pharmacology, natural products have provided critical insights into the molecular basis of pain sensation and helped to validate new targets for pain relief. Research has examined the effects of cannabis or cannabinoids on chronic pain, particularly neuropathic pain, and has found low‐ to moderate‐quality evidence that these medicines produced better pain relief than placebos [13, 14]. Resiniferatoxin (RTX), produced by euphorbias, is effective as a long‐duration, nonopioid single‐administration treatment for bone cancer pain [15]. In recent laboratory studies, conolidine, derived from Tabernaemontana divaricata, is efficacious in pain assays and appears to have analgesic properties; however, its mechanism of action remains unknown [16]. There is some evidence that enteric‐coated peppermint oil capsules may be modestly efficacious in reducing abdominal pain associated with irritable bowel syndrome (IBS) [17]. Devil’s claw and white willow bark (taken orally) may be helpful for low‐back pain over the short term [18]. Two compounds in kratom (Mitragyna speciosa) leaves, mitragynine and 7‐hydroxymitragynine, interact with opioid receptors in the brain, decreasing pain when taken in high doses [19]; however, to date, there are no clinical trials to evaluate the health effects of kratom or to determine if kratom is an effective or safe treatment for any pain condition or for opioid addiction. Figure 28.1 The integration of complementary and integrative health interventions with traditional drug‐based and/or surgical pain management [1]. Challenges in the assessment of plant products include their complexity and variability, including possible instability of active components or the presence of impurities, conflicting or unreliable conclusions in the literature, and low statistical power of studies [20]. Further, there is a paucity of data on the safety of many products, including the safety of their use in a 21st century context (e.g. if taken with modern prescription drugs) [20, 21, 22] and their appropriate use in the context of traditional or indigenous practices. Botulinum toxin may relieve pain by blocking substance P and calcitonin gene‐related peptide (CGRP) within the central nervous system, leading to reduction of central sensitization. It may also cause peripheral decreases of substance P, CGRP, glutamate, and TRPV receptor translocation, leading to a block of peripheral sensitization [23]. In addition, anthrax toxins are being studied as a molecular platform to target pain, and asymptomatic bacteriuria (ASB) strains of E. coli are being investigated for their analgesic properties [24]. There is some evidence that suggests some probiotics may improve abdominal pain from IBS; however, benefits have not been conclusively demonstrated, and not all probiotics have the same effects [25]. Snail venoms have potentially valuable effects, including inhibition of pain without the potential for addiction, but they are peptides, and delivery to target sites is challenging [26]. The one marketed pain medicine derived from snail venom, ziconotide (Prialt), cannot cross the blood‐brain barrier and therefore can only be administered intrathecally. For this reason, although ziconotide has advantages over morphine, it’s only used when morphine is not a possibility [27]. Pain relief is one of the many purported benefits of fish oil, but the mechanism by which fish oil might produce beneficial effects for pain is not well understood. Omega‐3 fatty acids and their specialized proresolving mediator (SPM) derivatives have both neuronal and immune actions because their receptors are expressed by different cell types, and thus, there is some evidence that they may help resolve both inflammation and pain [28]. Clinical trials on rheumatoid arthritis (RA) have found that fish oil supplements may help alleviate tender joints, while other studies have found that fish oil may reduce the daily nonsteroidal anti‐inflammatory drug requirement of RA patients [29]. Laboratory studies have demonstrated that pretreatment and continuous treatment with nicotinamide riboside (NR), a vitamin B isoform, prevents the tactile hypersensitivity associated with paclitaxel‐induced peripheral neuropathy, and behavioral testing has shown that animals treated with NR did not have an increase in pain behavior [30]. Riboflavin, also known as vitamin B2, has been demonstrated as safe and effective prophylactic therapy for the prevention of migraines, especially in adults [31]. The evidence base for the effectiveness of mind and body practices is still relatively incomplete, but a few rigorous examples where there is promise of usefulness and safety include acupuncture and tai chi for pain associated with osteoarthritis (OA) of the knee [32, 33, 34, 35]; massage for neck pain [36]; tai chi for fibromyalgia [37]; relaxation techniques for headaches and migraine [38, 39]; and acupuncture, massage, yoga, and spinal manipulation for chronic back pain [7, 40]. New research is shedding light on the effects of meditation and acupuncture on central mechanisms of pain processing and perception and regulation of emotion and attention [41]. Mindfulness. Mindfulness meditation has been found to significantly reduce pain in experimental and clinical settings and to improve a wide spectrum of clinically relevant cognitive and health outcomes, including for low‐back pain and fibromyalgia [7, 42, 43]. There is increasing evidence linking mindfulness techniques to improved immune function, but the findings require further replication [44], and there haven’t been enough large, high‐quality studies to determine long‐term effects in rheumatic disease [45, 46]. It is unclear if the analgesic mechanisms supporting mindfulness meditation are distinct from or parallel to those engaged by placebo and/or slow, rhythmic breathing; however, there is emerging evidence suggesting that mindfulness meditation engages multiple unique neural mechanisms not mediated by endogenous opioids to reduce pain [47]. Hypnosis. A growing body of evidence suggests that hypnosis may be useful to manage some painful conditions [48, 49]. Findings from a few studies have demonstrated that training patients in the use of self‐hypnosis significantly reduced their need for sedatives and analgesia when undergoing interventional radiological procedures [50]. Biofeedback. The efficacy of biofeedback has been evaluated in numerous studies for tension headaches, with positive results. Several studies have shown biofeedback decreased the frequency of both pediatric and adult migraines, with some showing an effect lasting over an average follow‐up phase of 17 months [51, 52]. Placebo. Contextual factors, including patient–clinician interactions and the expectation of benefit, can contribute to improvements in pain. Although this phenomenon is called the “placebo effect,” it can occur with any treatment, not just placebos, and may lead to enhanced outcomes [21, 53]. Understanding psychoneurobiological mechanisms underlying placebo analgesia may lead to shaping the clinician–patient relationship, reducing the use of analgesic drugs, and training the patient to become an active agent of the therapy [54]. Acupuncture. For patients with low‐back pain, acupuncture has been associated with lower pain intensity compared to usual care or simulated acupuncture [33]. Acupuncture can be a helpful and reasonable referral option for other chronic pain conditions [33], including fibromyalgia [55], headaches [33. 56], and OA [32, 57, 58]. Auricular acupuncture, either as a stand‐alone therapy or as an adjunct technique, has shown potential benefits for acute pain relief [59]. Spinal manipulation. Spinal manipulation has been shown to produce modest, short‐term effects on chronic low‐back pain [6, 7]. Other studies have found that spinal manipulation is as effective as other interventions for reducing pain and improving function [60, 61]. Massage. There is low‐ to moderate‐quality evidence that massage therapy is superior to nonactive therapies in reducing arthritis pain and improving functional outcomes [62]. Massage may provide short‐term relief from low‐back pain, but the evidence is not of high quality [11]. There is some evidence that massage has a positive effect on migraine, tension headaches, and neck pain [56, 63]. Meditative Movements. There is evidence that yoga and tai chi may be beneficial for patients with fibromyalgia [37]
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Complementary and Integrative Approaches for Pain Relief
Categories of Complementary and Integrative Health Approaches Based on Primary Therapeutic Input
Acupuncture and acupressure
A family of procedures involving stimulation of defined anatomic points, a component of the major Asian medical traditions; most common application involves the insertion and manipulation of thin metallic needles
Ayurvedic medicine
The major East Indian traditional medicine system; treatment includes meditation, diet, exercise, herbs and elimination regimens (using emetics and diarrheals)
Biofeedback
The use of electronic devices to help people learn to consciously control body functions such as breathing and heart rate
Herbs
Herbal supplements—sometimes called botanicals—are a type of dietary supplement containing one or more herbs.
Hypnosis
The induction of an altered state of consciousness characterized by increased responsiveness to suggestion
Massage
Manual therapies that manipulate muscle and connective tissues to promote muscle relaxation, healing and sense of well‐being
Meditation
A group of practices, largely based in Eastern spiritual traditions, intended to focus or control attention and obtain greater awareness of the present moment, or mindfulness
Mindfulness‐based stress reduction
A type of meditation initially developed to help manage stress, but which has evolved to encompass the treatment of a variety of health‐related conditions such as anxiety, depression and pain
Naturopathy
A clinical discipline that emphasizes a holistic approach to the patient, herbal medications, diet and exercise
Probiotics
Live microorganisms that are intended to have health benefits when consumed or applied to the body. They can be found in yogurt and other fermented foods, dietary supplements and beauty products.
Relaxation techniques
Relaxation techniques include a number of practices such as progressive relaxation, guided imagery, biofeedback, self‐hypnosis and deep breathing exercises. The goal is similar in all: to produce the body’s natural relaxation response, characterized by slower breathing, lower blood pressure and a feeling of increased well‐being.
Spinal manipulation
A range of manual techniques, employed by chiropractors and osteopathic physicians, for adjustments of the spine to affect neuromuscular function and other health outcomes
Tai chi
A mind and body practice originating in China that involves slow, gentle movements and sometimes is described as “moving meditation”
Traditional Chinese medicine
A medical system that uses acupuncture, herbal mixtures, massage, exercise and diet
Yoga
An exercise practice, originally East Indian, that combines breathing exercises, physical postures and meditation
Primary Dietary Input
Plant‐Derived
Microbial‐Derived
Marine‐Based
Animal‐Derived
Vitamins
Primary Psychological and Physical Input
Primary Psychological Input
Primary Physical Input
Psychological and Physical Input
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