Managing Noncancer-related Chronic Pain Without Opioids

Author: Luke Fortney, MD, Integrative Family Medicine, Meriter Medical Group, Madison, WI

Peer Reviewer: Nirmala R. Abraham, MD, FABPM, Medical Director, Sycamore Pain Management Center, Miamisburg OH

Chronic Pain Background

Managing chronic pain is a challenge for patients and clinicians alike, with 52% of chronic pain patients being treated solely by their primary care physician.1 Chronic myofascial pain affects 116 million American adults, which is more than heart disease, cancer, and diabetes combined.2 In 2010, an estimated $635 billion was spent on medical treatments and lost work productivity due to chronic pain.3 In 2005, the American Pain Foundation released a comprehensive report that estimated 9% of the U.S. adult population suffered from moderate-to-severe pain, with two-thirds of pain sufferers having had pain for more than 5 years. According to this report, more than 68% of all surveyed full-time employees — more than 80 million people — suffer from pain-related conditions, of which 18% is work-related. Meanwhile, more than half of full-time surveyed employees suffer from pain that is not due to work-related injuries. Fourteen percent of all full-time employees — more than 17 million people — took sick days in 1995 due to pain conditions, resulting in more than 50 million workdays.4 According to a cross-sectional study published in the Journal of the American Medical Association, more than half (52.7%) of the workforce surveyed reported having headache, back pain, arthritis, or other musculoskeletal pain in the previous 2 weeks, and 12.7% of all workforce lost productive time in a 2-week period due to pain.5 More recently, 76.5 million Americans reported that they experienced pain that persisted for more than 24 hours in the past month.6 However, the actual prevalence of myofascial pain syndromes varies, mostly based on variable diagnostic criteria and terminology. For example, differentiating myofascial pain from fibromyalgia clinically can be challenging, if not impossible, given the extensive overlap of comorbid and coexisting conditions such as fatigue, sleep disturbance, mood disorders, and other common disorders, including migraine headache and irritable bowel syndrome (IBS), that fall under the larger classification of central sensitization syndrome.7,8 Nonetheless, myofascial pain is widely considered the leading cause of musculoskeletal pain, and is the most widely used and general term that encompasses many different forms and types of chronic pain conditions. It has been found to affect up to 85% of the general population at some point in their lives.9 Women and the elderly (older than 65 years of age) appear to be more affected with pain syndromes in general, at 65% and 80% prevalence, respectively. This is compared to 37% prevalence in men from ages 30-60.10,11

The International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience associated with or without actual tissue damage.12 Predisposing factors for chronic pain can include a range of conditions such as musculoskeletal injury, sleep dysfunction, psychological and environmental stress, acute and chronic medical illnesses, prolonged immobility, lack of exercise, posture abnormalities, and nutritional or endocrine abnormalities.13 Comorbidities often include non-restorative sleep; chronic fatigue; stiffness; IBS; temporal mandibular joint syndrome; history of sexual, emotional, or physical abuse; and various mood disorders including depression, anxiety, and post-traumatic stress disorder (PTSD).14

The actual mechanisms leading to chronic pain syndromes are incompletely understood. Although chronic pain is a multifactorial condition with significant psychological and emotional influences, it is primarily a problem of central and peripheral somatosensory dysfunction. Investigators in the field of chronic pain generally agree that increases in pain sensitivity in myofascial pain syndromes such as fibromyalgia are the result of central nervous system augmentation of sensory input, as well as diminished central nervous system inhibitory pain function.15,16 Physiologically, chronic myofascial pain is related to sensitization of the motor-end-plate, which then sensitizes the mechanosensitive afferent nerves and their connection at the dorsal horn at the spinal cord. Once established, this pain process can have cortical effects such as thalamic asymmetry leading to spontaneous or stimuli-generated tissue hypersensitivity called central sensitization. As a result, patients with chronic myofascial pain may exhibit symptoms such as allodynia and hyperalgesia.17 In addition, many neuroendocrine and immune function alterations are often present. For example, cerebrospinal fluid levels of substance P can be elevated, which results in exacerbated pain sensation.18 Further dysfunction is present in the regulation of cortisol, adrenergic, serotonin, and growth hormone.19 There also appear to be increases in inflammatory cytokines, such as interleukin-2, with impaired lymphocyte and T cell function.20,21

Clinicians who work with patients with chronic pain often are aware of the sensitive temperament connection with pain symptoms in this patient population. Although there are likely genetic predispositions toward pain syndromes and hyperalgesia (for example, NMDA receptor variations), further research is needed. Nonetheless, familial and environmental factors do influence pain sensation, and research has shown that stressful life events are correlated with the development of chronic pain syndromes. For example, PTSD and other similar stressful life events and various other forms of trauma often are present as comorbidities. Careful history taking by the clinician often will reveal stress-related triggers, including an accident, illness, abuse history, relationship strain, environmental stress such as overwork, or negative emotional events such as the loss of a loved one.22,23 As a result, perceptions of pain are influenced by social, cultural, and psychological factors that produce variable nociceptive sensations in different people. The variable location and degree of pain symptoms is influenced by one's genetic predispositions, which is a risk factor for chronic pain as seen in family medical histories, as many patients exhibit higher than normal sensitivities to environmental factors as already mentioned. These personality traits often include being overly empathetic, having a high degree of self-criticism and judgment, having a strong personal drive with self-expectations that are perfectionistic, having a heightened desire to please and take care of others, and being hypersensitive to emotional cues of acceptance or rejection from others.24,25,26 Furthermore, predispositions for chronic pain often are expressed through stressful physical and emotional triggers that occur in the context of a society that places escalating expectations on increased productivity, which often comes at the expense of decreased self-care.27

The Opioid Dilemma

Conventionally, treatment of chronic pain has commonly involved escalating doses and dependence on opioid medications. In the 1980s, wider use of opioids for noncancer chronic pain increased significantly, which resulted in large quantities of opioids being diverted for nonmedical and inappropriate use.28 In 2003-2004, 23% of all emergency room visits resulted in an opioid prescription. Between 1988-1994 and 1999-2002, the age-adjusted percentage of women reporting prescribed narcotic drug use increased by from 3.6% to 5.3%. During this period, use of narcotic medications rose by almost 75% among women 45-64 years of age and by more than 50% among women age 65 years and older.1 A study using data from the National Ambulatory Medical Care Survey reported that opioid prescriptions in general increased from 4.1% (in 1992 and 1993) to 6.3% (1998 and 1999) of office visits to primary care providers.29 In 2012, the CDC reported that between 1999 and 2010, overall pharmacy sales of opioid analgesics increased fourfold.30 By 2011, hydrocodone was the most dispensed prescription medication in the United States at 131 million prescriptions.31

Although treating acute moderate-to-severe pain with opioid medications is efficacious and appropriate, using opioids for noncancer-related chronic pain has come into question, with increasing calls to avoid or reduce opioids for chronic noncancer pain when possible.32,33,34 Practitioner experience and a growing body of evidence suggest that treating noncancer-related nociceptive chronic pain with opioid medications may not be helpful in improving quality of life, pain reduction, or daily activity and function. There are data to suggest that chronic opioid use can decrease the pain threshold through the development of opioid-induced hyperalgesia.35 Prolonged opioid treatment not only results in a loss of anti-nociceptive desensitization, but also leads to activation of a pro-nociceptive sensitization known as hyperalgesia36 and irreversible gray matter changes.37 Another study from Denmark of more than 10,000 noncancer chronic pain patients concluded that opioid treatment of long-term/chronic noncancer pain does not fulfill any key outcome treatment goals of pain relief, improved quality of life, nor improved functional capacity.38 Similarly, a 2009 review found that a 423% increase in spending for opioid medications to treat low back pain was not accompanied by any improvement in patient outcomes or disability rates (See Table 1).33

Opioid abuse and misuse, adverse effects, escalating doses, overdose, and death are concerning challenges seen with increasing widespread opioid availability. In 2008, nearly 10% of high school seniors in the United States self-reported recreational use of hydrocodone.39 A study published a year later reported that one in five high school-aged teens abused a prescription medication at least once.40 Furthermore, teenagers admit that obtaining prescription opioids is "very easy." Similarly in 2009, 2.6 million Americans, approximately 7000 Americans per day, used prescription medications recreationally for the first time.41 Among chronic pain patients, a review of 67 studies found that 3% develop opioid addiction while 12% show aberrant drug-related behavior.42 Overall, the United States Substance Abuse and Mental Health Services Administration found that 53% of people obtained their recreational narcotics from a friend or relative, and 10.6% purchased them from someone they knew.43 In 2007, a study by the Florida Medical Examiners Commission concluded that hydrocodone and oxycodone caused more than twice as many deaths as cocaine, heroin, and methamphetamine combined. In comparison, the percentage of people admitted for alcohol abuse treatment dropped during this same time period by 5%. Similarly, admissions to hospitals and treatment programs for the treatment of cocaine abuse dropped by 16%.44 In practical figures, in 2012, the CDC reported that for every opioid medication overdose, nine people are admitted for opioid abuse treatment, 35 are seen in emergency department visits, 161 report drug abuse or dependence, and 461 report recreational and non-medical use of opioid medications.29

In addition to becoming the fastest growing drug problem in the United States, opioid-related morbidity and mortality is now recognized as a growing epidemic, with prescription opioids accounting for 70% of all misused and diverted narotics.45 In more general terms, total adverse drug reactions are the sixth leading cause of death in the United States, estimated at 106,000 per year.46 Between 1997-2002, there was nearly a 100% increase in opioid-abuse related death, with oxycodone use increasing by 727%. This public health study and the Office of National Drug Control Policy have concluded that continuing dramatic increases in the availability of such opioids have made their abuse a major growing problem.47,48 Morbidity and Mortality Weekly Report concluded that unintentional drug poisoning mortality rates increased substantially in the United States during 1999-2004 and can be attributed primarily to increasing numbers of deaths associated with prescription opioid analgesics such as oxycodone. In 2004, nearly 10,000 cases of unintentional opioid-related deaths were reported, which increased by 54.6% from 1999.49 From 2003-2012, more overdose deaths have involved prescription opioid analgesics than heroin and cocaine combined.29

Curbing Opioid Therapy

Establishing a therapeutic relationship with chronic pain patients is the cornerstone of non-opioid based therapy. Primary care medicine is particularly well poised to address the opioid dilemma for this reason.50 Continuity of care, integrated electronic health records, strictly managed limited-quantity opioid prescriptions, and enhanced monitoring of opioid prescriptions by pharmacies and insurance companies are a few of the emerging safeguards that can help avoid escalating and misappropriated opioid medications.29 Referral to detoxification (methadone) clinics for illegal or prescription narcotic abuse and addiction is necessary in appropriate cases when identified (not reviewed here). Patient education that explains opioid-related hyperalgesia, allodynia, and opioid-induced hyperalgesia in ways that are understood by the patient is essential. Often this requires several visits and taking more time to adequately address the patient's questions. It is also important to recruit support from clinical staff, colleagues, and consultants.51 Clear communication and opioid/treatment plan contracts are helpful in this process. Specifically, it is helpful to offer three options to patients with noncancer chronic pain who are taking opioids on a daily basis:

1) Strict opioid non-escalation with limited-quantity, no-refill opioid prescriptions with frequent review of a pain contract with patients, or referral to a pain management specialist who can help manage opioid needs and offer other non-opioid therapy options;

2) Taper opioids over a predetermined period of time with clinical team support (may include opioid substitution — for example with tramadol or naltrexone) and initiate a pain treatment plan with active patient participation;

3) For the patient who is unsatisfied with these options and expresses desire to establish care with a different primary care physician, assistance should be offered to help with transition of his/her medical care (see Figure 1).

Through this process, it is important to repeatedly impress upon the patient that his/her pain is real, and that dependence on daily and long-term use of opioid medications will not improve quality of life or decrease long-term pain symptoms; in fact, it may result in worse pain or other side effects over time. It is important to emphasize that team-based, non-opioid approaches that combine relevant aspects of manual therapies, lifestyle changes, and mind-body therapies will take patience and persistence to yield positive results. For patients with opioid dependence, it is recommended to begin tapering doses over several weeks in a predetermined period of time. Similarly, substituting weak opioids with pharmacist or pain management specialty input as needed may be helpful. One study found that the use of tapering tramadol doses for heroin addiction for the treatment of withdrawal was superior to buprenorphine with reduced withdrawal symptoms over time, as well as a small number of side effects.52

Complementary Therapies

Massage Therapy

In addition to other non-opioid medications and supplements for the treatment of chronic pain (not reviewed here), increasing evidence suggests that non-pharmaceutical adjunctive therapies are widely used by patients and also should be considered by physicians for the management of pain. For example, one study of licensed complementary and alternative practitioners revealed that 20% of massage therapy sessions were made for back and neck pain alone.53 Manual therapies such as massage can reduce myofascial pain through upregulation of oxytocin, serotonin, and dopamine along with reduction of cortisol, epinephrine, and norepinephrine through the activation of the parasympathetic nervous system with resultant myofascial release and relaxation.54,55 Improvements in circulation, range of motion, and immune function through self or practitioner-assisted massage are other well-known benefits of various forms of massage therapy.56 Although, in general, the research literature for massage therapy contains shortcomings in quality and rigor — particularly with reviews, which often lack a definition, description, or rationale for the technique in question — there is emerging evidence in support of efficacy and safety. A systematic review of 19 studies of massage therapy for the treatment of myofascial neck pain concluded that massage therapy was safe. This review did not find any advantage of massage therapy compared to other treatments.57 However, a 2001 randomized controlled trial (RCT) found that the benefits of 10 massage treatments for the treatment of back pain were still significant 10 months after the last therapy session.58 Another RCT evaluating massage therapy for chronic neck pain revealed long-term improvements in pain symptoms and function, as well as decreased medication use.59

Manipulative Therapy

In a review of 43 RCTs evaluating chiropractic manipulation treatment (CMT) for chronic low back pain, 30 favored manipulation therapy over conventional care, while 13 reported no significant difference. None of the trials reported inferior outcomes with manipulation.60 A meta-analysis of RCTs using osteopathic manipulative treatment (OMT) for acute low back pain concluded that OMT significantly reduces low back pain in the short and long term.61 However, it is important to note that the evidence is strongest for OMT in the acute pain setting with decreased use of medications and physical therapy at little additional cost.62,63,64 Other less rigorous research suggests benefit of OMT in fibromyalgia and acute and chronic headache.65-67 It should be noted that manipulative therapy is considered quite safe. One review found that worsening disk disease occurs in fewer than 1 in 3.7 million patients undergoing manipulative therapy. Further, the reported incidence of iatrogenic stroke or vertebral artery dissection from high-velocity manipulative techniques is as low as 1 in 5.85 million. It is important to note that most injuries are known to occur when patients are treated by an untrained professional.68 Ideally, primary care physicians should collaborate with osteopathic colleagues and physical/occupational therapists (PT/OT) who specialize in manual therapies.


Compared to conventional approaches to pain management, acupuncture generally has less risk, harm, and expense. A systematic review of the world literature on nine prospective acupuncture safety studies involving tens of thousands of treatment sessions revealed two cases of pneumothorax and no incidence of infection.69 Comparison analyses of studies involving epidural steroid injections or acupuncture for low back pain reveal decreased cost and increased pain relief with the latter (see Table 2). In particular, acupuncture showed a 10-15% improvement at 12 and 24 months when compared with usual standard of care.70,71 In comparison, epidural steroid injections showed no improvement in low back pain symptoms at 12 and 26 weeks,72,73 despite being nearly 40 times as expensive as acupuncture in Quality Adjusted Life Year costs.74 A cost effectiveness study that evaluated acupuncture for the treatment of headache in the United Kingdom found that acupuncture improved health-related quality of life and was relatively cost effective.75 Similarly, in a study of 401 patients with chronic headache, compared to standard of care, on average acupuncture treatments resulted in 22 fewer headaches per year with 15% fewer medications and 26% fewer physician visits. Further, the pain-relieving effects of acupuncture were long lasting, with 34% improvement in headache symptoms at 12 months when compared to 16% in the standard of care control group.76 Acupuncture also has demonstrated benefit for the relief of more general myofascial pain syndrome in a controlled trial of gentle, superficial Japanese-style technique.77 Many physicians, PTs, and OTs have received training in medical acupuncture, which is becoming more widely available.

Trigger Point Therapy and Prolotherapy

Myofascial trigger point (TrP) therapy is another useful approach to pain relief that has similarities to acupuncture. One study proposed a 70% correlation between acupuncture points and conventional trigger points.78 TrP therapies encompass several varieties, which are largely based on the original work of Simmons and Travell.79 The simplest varieties of TrP encompass less invasive approaches such as myofascial release, low-level laser therapy, biostimulation, and thermotherapy. Often, these gentle and very safe approaches lend themselves well in combination with other therapies.80 Dry needling technique has been shown to inactivate localized TrP areas and improve pain sensitivity of other satellite TrPs, as well improve function and range of motion.81 Injection techniques that introduce various pharmaceutical agents into tendons, ligaments, joint spaces, and muscle are variably effective. Increased caution should be used when using corticosteroids and botulinum toxin type A due to increased harm potential.

Prolotherapy is a unique form of TrP therapy that involves injecting small amounts of irritant solutions into painful areas. The most common and safest solution contains varying mixtures of hypertonic glucose, saline, and lidocaine, which stimulate the release of growth factors and chemotactic attraction of inflammatory mediators favoring soft tissue healing.82 It is postulated that dextrose injections target peripheral nociceptors responsible for pain and neurogenic inflammation. Irritant solutions such as dextrose have a capsaicin receptor antagonist effect, which are expressed on peptidergic C-fibers that innervate joint synovium tissue. It is now recognized that sensitization of these peptidergic C-fibers, also called sensocrine neurons, play an important role in the development of pain. Prolotherapy has a neuromodulating effect on sensitized sensocrine neurons allowing for physiological tissue repair, including chondrocytes, but further research is needed.

Nonetheless, research in prolotherapy has accelerated significantly, with improvements in methodological quality and rigor.83 For non-specific low back pain, two RCTs reported positive results with more than 50% improvement in pain/disability scores at 6 months.84,85 The strongest data supporting prolotherapy are for chronic tendonopathies. A RCT evaluating prolotherapy for chronic lateral epicondylosis (tennis elbow) demonstrated improvements in pain relief and strength compared to controls, with results showing stability at 52 weeks.86 Achilles tendonopathy is another overuse injury that lends itself well to prolotherapy, according to a well-designed case series. In this study, participants reported decreased pain at rest and activity at 52 weeks.87 In patients with osteoarthritis (OA), prolotherapy appears to benefit both pain and function at 52 weeks in patients with at least 3 months of symptomatic knee pain. In this case series, there were no reported adverse effects and overall patient satisfaction was high.88


Being sedentary with low physical activity levels is linked to progressive myofascial pain. However, research demonstrates the development of hypoalgesia after regular aerobic exercise.89 Many meta-analyses report exercise to have a positive effect on pain symptoms, aerobic capacity, and physical function. Although the exact mechanisms behind these effects are not completely understood, exercise is thought to improve pain symptoms through its positive effect on weight reduction, enhanced sleep, aerobic conditioning, and improved mood.90

Recommendations for exercise in patients with chronic pain should be a part of every treatment plan. However, it is important to introduce exercise slowly, with recommendations to begin with light intensity for short periods of time to minimize or avoid post-exercise pain flares, which is defined as having increased pain 2 or more hours after exercise compared to baseline pain levels. However, exercise counseling should be based on patient preferences and needs, with adaptations and modifications being made as needed. For example, one study demonstrated improved pain scores in patients with fibromyalgia after a period of self-selected daily physical activities.91 For deconditioned patients, which is common with chronic pain, two exercise sessions of 10 minutes during the day can be a starting point.92 Lower-intensity activity — such as land or water walking, or gentle tai chi or yoga — should take place over longer periods of time, such as 30-60 minutes as tolerated and titrated up over time.93 According to a 2008 systemic review, aerobic exercise improves physical function and reduces pain symptoms in patients with fibromyalgia.94 In particular, pool exercise should be considered for many chronic pain patients in that it provides as much physical fitness and pain reduction over time as land-based exercise. Additional benefits from pool exercise include myofascial support from the water and improved psychological symptoms.95 In addition, tai chi and qi gong, very slow and gentle forms of martial arts, have shown benefit in improving pain and quality of life for chronic pain.96 Similarly, gentle yoga appears to be beneficial as well.97 One RCT involving 101 patients with chronic low back pain found that 12 weekly sessions of yoga improved symptoms and function at 26 weeks compared to exercise and self-care education. A study funded by the National Center for Complementary and Alternative Medicine using yoga for the treatment of chronic low back pain demonstrated decreased functional disability, pain, and depression at 12 and 24 weeks.98 Further, yoga therapy was associated with decreased medication use.99 Another RCT demonstrated significant reduction in pain scores and improved spinal flexibility for participants with chronic low back pain when compared to wait-list controls enrolled in a general physical exercise group.100


The standard American diet (SAD) has changed dramatically for the worse during the last 50 years, with significant increases in sugar, simple carbohydrates, overall calories, and artificial additives with resultant increases in systemic inflammatory processes called meta-inflammation.101 This term describes the chronic, low-grade, metabolically induced, inflammatory cascade that is mediated by the same molecules and markers of inflammation that results in chronic diseases such as cardiovascular disease and arthritis. It is telling that more than 90 million Americans are affected by chronic diseases related to meta-inflammation, which accounts for 70% of all deaths and 75% of medical care costs.102 Furthermore, it is estimated that 60% of chronic disease could be prevented by eating a healthy diet.103 Specifically with pain, research has shown that eating a vegetarian diet rich in omega-3 fatty acids (see Figure 2) can decrease the number of tender and swollen joints in rheumatoid arthritis, with average decreases in pain symptom scores by more than 30%.105,106 For myofascial pain syndromes such as fibromyalgia and low back pain, eating a vegan diet can improve overall pain symptoms.107 One correlation is that the enzyme phospholipase A2 — which is more than 20 times more active in lumbar disk tissue — is stimulated significantly by proinflammatory omega-6 fatty acids from the SAD diet, resulting in worse pain symptoms.108

It is important to note here that, in the case of OA for example, abnormal physiologic and metabolic pathways — and not solely "wear and tear" and advancing age as once thought — are considered principle factors in progression of the disease. Imbalances facilitated by systemic proinflammatory cytokines, eicosanoids, prostaglandins, and many other chemical mediators appear to play a central role in susceptibility and progression of pain sensitivity. In total, the combination of a sedentary lifestyle, obesity, and a SAD diet creates a vicious cycle of disease progression and worsening pain ensues.109,110

Recent interest in the role of glutamate on pain activating NMDA receptors in the central nervous system has suggested that diets low in aspartame, monosodium glutamate, and other artificial food additives may be helpful in treating some forms of chronic pain, such as fibromyalgia.111 Although further research is needed, evidence is lacking to suggest one particular diet over another for the treatment of various pain syndromes. However, an anti-inflammatory diet based on fewer overall calories, less sugar, substituting other fats with omega-3 fatty acids, and more plant-based whole foods may be most practical and helpful. Recommending a persistent and patient course of exercise and eating an anti-inflammatory or Mediterranean-type diet112 is nevertheless essential for improved overall health and concomitant pain relief over time. Weight loss should be emphasized with regular and close follow-up for patients with a body mass index (BMI) > 30 using this same approach. One study found that a combination of moderate exercise and modest weight loss provided more improvements in pain and function than either intervention alone.113 Partnering with patients using motivational interviewing, coaching, and collaboration with a dietician is encouraged.

Mind-Body Therapy

Mind-body interventions such as mindfulness meditation, psychology, biofeedback, and journaling can significantly reduce pain, improve physical function, and improve mood, and are considered very safe. A meta-analysis of 34 trials evaluating biofeedback for migraine headache compared to medications found similar improvements for both treatment options. Another review found that biofeedback was superior to medications in treating migraine headache in children.114 Biofeedback also has demonstrated decreased pain symptoms in fibromyalgia when compared to standard of care.115 In another study, 90 chronic pain patients trained in mindfulness meditation over 10 weeks showed significant reductions in pain symptoms and mood disturbance such as anxiety and depression. Use of pain medication decreased and activity levels and feelings of self-esteem increased, while a comparison group did not show significant improvement.116 These benefits were maintained at 15 months post-meditation training.117 Similarly, another study found that teaching affective awareness through journaling to patients with fibromyalgia significantly reduced pain symptoms at 6 weeks and 6 months.118 Resources for meditation and emotional awareness in clinical settings are evidence-based and widely available.119,120

Often unrecognized, pain also has psychological and emotional components that are easily left unaddressed. For example, early childhood abuse is associated with increased chronic pain and IBS symptoms.121 More specifically, childhood abuse is present in 54% of chronic pain patients compared to 21% of controls.122 Not only are there complex interactions among early abuse, stressful life events, depression, and the occurrence of chronic pain,123 but the effects of childhood abuse appear to last a lifetime.124 Traumatic life events can result in dysregulation of the inflammatory response system that can be triggered by subsequent life stressors that result in activation of pain symptoms. One study indicates that neonates who receive more heel sticks have lower pain thresholds later in life.125 Furthermore, 37% of patients with fibromyalgia and IBS also have a history of PTSD, and many more have subclinical symptoms.126,127,128 Among military veterans with PTSD, 80% also report chronic pain.129 Inversely, self-injurious patients who engage in cutting behavior have been shown to activate the dorsolateral prefrontal cortex region of the brain, which decreases pain sensations when compared to controls.130 Another study reported that activation of the prefrontal cortex region correlated positively with symptom improvement in patients with IBS who were given a placebo.131 Therefore, it is striking to correlate these findings with the effects of mindfulness training on negative affect — such as anxiety — and immune function. In a wait-list controlled study, participants trained in mindfulness over 8 weeks were found to have decreased negative affect, increased positive affect, increased immune response, and increased prefrontal cortex activity when compared to controls.132 In a direct study on the effect of emotional awareness using journaling and mindfulness practices in patients with fibromyalgia, the study group had significantly lower pain severity, higher physical function, and higher tender-point threshold at 6 months compared to controls. Nearly half of participants in this study had at least a 30% reduction in pain severity compared to baseline.118 This suggests that activation of the prefrontal cortex and other central structures can be learned over time, which may have a pain dampening effect. For example, a 5-year follow-up study of 213 patients with chronic low back pain revealed that those who participated in cognitive behavioral therapy had reduced pain, increased physical activity, improved quality of life, and overall better health. There was also a reduction in total overall medical costs and missed days of work.133 This and other forms of health-psychology can be useful and are essential for the successful management of chronic pain.

Many forms of chronic pain such as fibromyalgia, myofascial low back pain, and migraine headaches have common pathophysiology involving sensitization of the central and peripheral nervous systems, with augmented neuroendocrine and immune dysregulation.8 In other words, there are areas of the brain that are involved in processing, increasing, and decreasing pain. As in the case of phantom limb, pain can and often does originate centrally in the absence of tissue injury or disorder. Whether initiated centrally or peripherally, the pain is real. Many types of pain, such as low back pain and headache, often are started from traumatic life events, and then subsequently triggered by daily life stressors. Explaining this process to patients with chronic pain can often be helpful and therapeutic.134 John Sarno, MD, from New York University has written widely about this process, which he calls tension myoneuronal syndrome (TMS). Through a complex interaction of the autonomic nervous system, central brain structures, such as the anterior cingulate cortex and various negative affective emotions, somatic pain symptoms become entrenched and chronic. It is important to note that although this type of pain is not associated with tissue damage, it is nonetheless real pain. According to Sarno and others, physical pain in this setting — after a comprehensive rule-out medical evaluation — is unconsciously substituted for intolerable or inescapable emotional pain (see Figure 3). Further, he asserts that patients who learn about this process realize a reduction or elimination of their pain. However, a certain level of self-awareness and acceptance of this explanation of the mind-body connection is required to realize pain relief. Emotional awareness therapy therefore requires screening for appropriate candidates, education and counseling, and a degree of self-motivation to engage in exercises such as journaling, reading, counseling, and meditation. In addition to pain psychology referral and collaboration, there are several effective resources that clinicians can recommend to patients (see Table 3).


Creating a Chronic Pain Health Plan

Offering patients the opportunity to play an active role in their treatment by selecting one of several complementary treatments from various options in the areas of manual therapy, exercise, and mind-body medicine can result in a synergistic effect that goes beyond the individual benefits of each modality when administered separately.74 Specific therapies should be matched to the unique needs, culture, and beliefs of each patient based on insight obtained during an initial long-office visit. Opioid medications should be avoided, substituted, or tapered. According to the 2009 National Institute on Health and Clinical Excellence (NICE) report, pain management strategies should consider non-pharmacologic means such as exercise, biofeedback, relaxation techniques, and manual therapies including acupuncture, manipulation, and massage.135 A multidisciplinary team-based approach can be an especially useful and effective strategy for managing chronic pain.50 For example, an RCT involving 207 patients with fibromyalgia found that combining exercise with a facilitated self-help educational class resulted in better symptom control than either intervention alone.136 An evidence-based estimate of number needed to treat (NNT) for the treatment of chronic low back pain using manipulation is 5.4. Moreover, the NNT is 5.1 for exercise and 3.3 when combining exercise with manipulation.137

Establishing a positive therapeutic relationship with the patient can result in pain reduction by as much as 28.4%, which is similar to morphine.138 To this aim, clinicians are encouraged to guide, coach, and facilitate self-management strategies that empower patients to take control of their health and symptoms,139 while at the same time directing patients away from dependence on opioid medications. This educational process can be facilitated by asking the patient to identify the primary "problem" or area of focus that is most important to him/her. This "central issue" or main concern can then be addressed in a comprehensive way by addressing eight main areas that directly influence both the etiology and treatment (see Figure 4). These areas draw from external physical factors — such as medications, supplements, nutrition, exercise, manual therapies, and environment — as well as the internal factors of belief, thoughts, emotions, and memories.50,140 This framework — Step 1 Awareness — sets the stage where the patient begins to see and understand the various factors that influence pain severity, with particular emphasis on recruiting active patient participation in creating a health plan that draws from all aspects of the healing process. Rather than being told what to do, the patient may instead discover the obstacles to recovery for himself/herself (e.g., being sedentary, tobacco use, abusive environment). From here, the patient may choose what particular therapies — Step 2 Action — from the three areas of pain treatment (manual therapy, exercise, and mind-body medicine) to begin working with. Close and regular follow-up with various members of the health team is important to ensure treatment adherence and to address any areas where further help is needed (see Figure 1).


The use of opioids for the treatment of noncancer chronic pain should be discouraged and avoided when possible. Coordinating safe and effective treatments for noncancer chronic pain that avoid opioids should draw on physical and mind-body disciplines that are efficacious and generally regarded as safe. Building a stable network of various referral partners with expertise in these areas is a necessary step in creating successful and efficient treatments that honor the individual needs of each patient, while at the same time maintaining a firm sense of patient accountability. Setting intention and being clear with patients about pain management goals up front is important. By offering an individualized health plan that emphasizes active patient participation, the clinician can achieve greater treatment adherence from the patient. Increased face-to-face time at the onset of treatment also facilitates a stronger patient-clinician relationship by allowing the patient to tell her/his personal story, which engenders a feeling of being recognized and heard, which alone has therapeutic benefit and should be supported.141 (See Table 4.)


1. CDC. Chartbook on Trends in the Health of Americans Health. United States, 2006; 80. Available at: Accessed Oct. 5, 2012.

2. Board on Health Sciences Policy. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. 2011. Available at: Accessed Oct. 5, 2012.

3. American Acadamy of Pain Medicine: AAPM Facts and Figures on Pain. Available at: Accessed Oct. 5, 2012.

4. American Pain Foundation. Pain Facts, An overview of American pain surveys. [Brochure] Updated March 2005.

5. Stewart WF, et al. Lost productive time and cost due to common pain. JAMA 2003;290:2443-2454.

6. American Pain Foundation. Provider Prescribing Patterns and Perceptions: Identifying Solutions to Build Consensus on Opioid Use in Pain Management—A Roundtable Discussion [Brochure]. Baltimore, MD; 2008: 2.

7. Pearce JM. Myofascial pain, fibromyalgia or fibrositis? Eur Neurol 2004;52:67-72.

8. Yunus MB. Fibromyalgia and overlapping disorders: The unifying concept of central sensitivity syndromes. Seminars Arthr Rheum 2007;36:339-356.

9. Staud R. Future perspectives: Pathogenesis of chronic muscle pain. Best Pract Res Clin Rheumatol 2007;21:581-596.

10. Drewes AM, Jennum P. Epidemiology of myofascial pain, low back pain, morning stiffness and sleep-related complaints in the general population. J Musculoskelet Pain 1995;3(Suppl 1):121.

11. Podichetty VK, et al. Chronic non-malignant musculoskeletal pain in older adults: Clinical issues and opioid intervention. Postgrad Med J 2003;79:627-633.

12. International Association for the Study of Pain. Available at: Accessed Oct. 5, 2012.

13. Bonakdar RA. Myofascial Pain Syndrome. In: Rakel D, ed. Integrative Medicine. 3rd Edition; ch 62. Philadelphia: Saunders/Elsevier; 2012.

14. Sullivan MD, et al. Association between mental health disorders, problem drug use, and regular prescription opioid use. Arch Intern Med 2006;1662087-2093.

15. Bradley LA. Pathophysiologic mechanisms of fibromyalgia and its related disorders. J Clin Psychiatry 2008;69(Suppl 2):6-13.

16. Gracely RH, et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 2002;46:1333-1343.

17. Richeimer SH, ed. Integrative Pain Medicine. Totowa, NJ: Humana Press; 2008: ch 2.

18. Russell IJ, et al. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994;37:1593-1601.

19. Neeck G, Crofford LJ. Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am 2000;26:989-1002.

20. Ross RL, et al. Preliminary evidence of increased pain and elevated cytokines in fibromyalgia patients with defective growth hormone response to exercise. Open Immunol J 2010;3:9-18.

21. Hader N, et al. Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome. Arthritis Rheum 1991;34:866-872.

22. Amir M, et al. Post-traumatic stress disorder, tenderness and fibromyalgia. J Psychosom Res 1997;42:607-613.

23. Cohen H, et al. Prevalence of post-traumatic stress disorder in fibromyalgia patients: Overlapping syndromes or post-traumatic fibromyalgia syndrome? Semin Arthritis Rheum 2002;32:38-50.

24. Aron EN, Aron A. Sensory-processing sensitivity and its relation to introversion and emotionality. J Pers Soc Psychol 1997;73:345-368.

25. Aron EN. Revisiting Jung's concept of innate sensitiveness. J Anal Psychol 2004;49:337-367.

26. Sarno J. Mindbody Prescription. New York: Warner Books; 1998: chapter 1.

27. Mork PJ, et al. Association between physical exercise, body mass index, and risk of fibromyalgia: Longitudinal data from the Norwegian Nord-Trøndelag Health Study. Arthritis Care Res (Hoboken) 2010;62:611-617.

28. Nelson LS, Perrone J. Curbing the opioid epidemic in the United States: The risk evaluation and mitigation strategy (REMS). JAMA 2012;308:457-458.

29. Centers for Disease Control and Prevention (CDC). CDC Grand Rounds; prescription drug overdoses-a US epidemic. MMWR Report 2012;61:10-13.

30. Olsen Y, et al. Opioid prescriptions by US primary care physicians from 1992-2001. J Pain 2006;7:225-235.

31. IMS Health survey. Available at: Accessed Oct. 5, 2012.

32. Chou R, et al. Research gaps on use of opioids for chronic noncancer pain: Findings from a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. J Pain 2009;10:147-159.

33. Deyo RA, et al. Overtreating chronic back pain: Time to back off? J Am Board Fam Med 2009;22:62-68.

34. Martell BA, et al. Systematic review: Opioid treatment for chronic back pain: Prevalence, efficacy, and association with addiction. Ann Intern Med 2007;146:116-127.

35. Liang D, et al. Chronic morphine administration enhances nociceptive sensitivity and local cytokine production after incision. Mol Pain 2008;22:4-7.

36. Chen L, et al. Altered quantitative sensory testing outcome in subjects with opioid therapy. Pain 2009;143:65-70.

37. Younger JW, et al. Prescription opioid analgesics rapidly change the human brain. Pain 2011;152:1803-1810.

38. Eriksen J, et al. Critical issues on opioids in chronic noncancer pain: An epidemiological study. Pain 2006;125:172-179.

39. National Institute on Drug Abuse. Available at: Accessed Oct. 5, 2012.

40. Key Findings of the 2009 Partnership: Metlife Foundation Attitude Tracking Study (PATS). Available at: Accessed Oct. 5, 2012.

41. National Survey on Drug Use and Health: Volume 1: Summary of National Findings (SAMHSA) 2009. Available at: Accessed Oct. 5, 2012.

42. Fishbain DA, et al. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review. Pain Medicine 2008;9:444-459.

43. National Survey on Drug Use and Health Report: How Young Adults Obtain Prescription Pain relievers nor nonmedical use. Issue 39, 2006. Available at: Accessed Oct. 5, 2012.

44. Paulozzi LJ, et al. Vital signs: Overdoses of prescription opioid pain relievers — United States, 1999-2008. MMWR 2011;60;1487-1492.

45. Zgierska A, et al. Patient satisfaction, prescription drug abuse, and potential unintended consequences. JAMA 2012;4:1377-1378.

46. Lazarou J, et al. Incidence of adverse drug reactions in hospitalized patients. JAMA 1998;279:1200-1205.

47. Paulozzi LJ. Sharp rise in opioid analgesic involvement in drug abuse deaths in American metropolitan areas. Am J Public Health 2006;96:1755-1757.

48. Office of National Drug Control Policy: Epidemic, responding to America's prescription drug abuse crisis, 2011. Available at: Accessed Oct. 5, 2012.

49. Centers for Disease Control and Prevention. Unintentional Poisoning Deaths — United States, 1999–2004. Morbidity and Mortality Weekly Report 2007;56:93-96.

50. Fortney L, et al. Introduction to integrative primary care: The health-oriented clinic. Prim Care 2010;37:1-12.

51. Gottlieb K, et al. Transforming your practice: What matters most. Fam Pract Manag 2008;15:32-38.

52. Threlkeld M, et al. Tramadol versus buprenorphine for the management of acute heroin withdrawal: A retrospective matched cohort controlled study. Am J Addictions 2006;15:186-191.

53. Cherkin DC, et al. Characteristics of visits to licensed acupuncturists, chiropractors, massage therapists, and naturopathic physicians. J Am Board Fam Pract 2002;15:463-472.

54. Uvnas-Moberg K, Petersson M. Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing. Psychosom Med Psychother 2005;51:57-80.

55. Field TM. Massage therapy effects. Am Psychologist 1998;53:1270-1281.

56. Braverman DL, Schulman RA. Massage techniques in rehabilitation medicine. Phys Med Rehabil Clin N Am 1999;10:631-649.

57. Haraldsson BG, et al. Massage for mechanical neck disorders. Cochrane Database Syst Rev 2006;(3):CD004871.

58. Cherkin DC, et al. Randomized trial comparing traditional Chinese medical acupuncture, therapeutic massage, and self-care education for chronic low back pain. Arch Intern Med 2001;161:1081-1088.

59. Sherman KJ, et al. Randomized trial of therapeutic massage versus self-care book for chronic neck pain. Presented at North American Research Conference on Complementary and Integrative Medicine, Edmonton, May 23-26, 2006.

60. Meeker WC, Haldeman S. Chiropractic: A profession at the crossroads of mainstream and alternative medicine. Ann Intern Med 2002;136:216-227.

61. Licciardone JC, et al. Osteopathic manipulative treatment for low back pain: A systematic review and meta-analysis of randomized controlled trials. BMC Musculoskelet Disord 2005;6:43.

62. Andersson GBJ, et al. A comparison of osteopathic spinal manipulation with standard care for patients with low back pain. N Engl J Med 1999;341:1426-1431.

63. Williams NH, et al. Randomized osteopathic manipulation study (ROMANS): Pragmatic trial for spinal pain in primary care. Fam Pract 2003;20:662-669.

64. Licciardone JC, et al. Osteopathic manipulative treatment for chronic low back pain: A randomized controlled trial. Spine (Phila Pa 1976) 2003;28:1355-1562.

65. Gamber R, et al. Osteopathic manipulative treatment in conjunction with medication relieves pain associated with fibromyalgia syndrome: Results of a randomized clinical pilot project. J Am Osteopath Assoc 2002;102:321-325.

66. Hoyt W, et al. Osteopathic manipulation in the treatment of muscle-contraction headache. J Am Osteopath Assoc 1979;78:322-325.

67. Anderson RE, Sensical C. A comparison of selected osteopathic treatment and relaxation for tension-type headaches. Headache 2006;46:1273-1280.

68. Gibbons P, Tehan P. HVLA thrust techniques: What are the risks? Int J Osteopath Med 2006;9:4-12.

69. Edzard E, White AR. Prospective studies of the safety of acupuncture: A systematic review. Am J Med 2001;110:481-485.

70. Thomas KJ, et al. Randomized controlled trial of short course of traditional acupuncture compared with usual care for persistent non-specific low back pain. BMJ 2006 23;333:623.

71. Ratcliffe J, et al. A randomized controlled trial of acupuncture care for low back pain: Cost effectiveness analysis. BMJ 2006;333:626.

72. Arden NK, et al. A multicentre randomized controlled trial of epidural corticosteroid injections for sciatica: The WEST study. Rheumatology 2005;44:1399-1406.

73. Price C, et al. Cost-effectiveness and safety of epidural steroids in the management of sciatica. Health Technol Assess 2005;9:1-58.

74. University of Wisconsin Department of Family Medicine Integrative Medicine module on low back pain. Available at: Accessed Oct. 5, 2012.

75. Wonderling D, et al. Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care. BMJ 2004;328:747.

76. Vickers AJ, et al. Acupuncture for chronic headache in primary care: Large, pragmatic, randomised trial. BMJ 2004;328:744.

77. Birch S, Jamison RN. Controlled trial of Japanese acupuncture for chronic myofascial neck pain: Assessment of specific and nonspecific effects of treatment. Clin J Pain 1998;14:248-255.

78. Melzack R, et al. Trigger points and acupuncture points for pain: Correlations and implications. Pain 1977;3:3-23.

79. Simmons D, et al. Trigger Point Manual. Vol 1.,2nd ed. Baltimore: Williams & Wilkins; 1999.

80. Hou CR, et al. Immediate effects of various physical therapeutic modalities on cervical myofascial pain and trigger-point sensitivity. Arch Phys Med Rehabil 2002;83:1406-1414.

81. Hsieh YL, et al. Dry needling to a key myofascial trigger point may reduce the irritability of satellite MTrPs. Am J Phys Med Rehabil 2007;86:397-403.

82. Banks A. A rationale for prolotherapy. J Orthop Med 1991;13:54-59.

83. Rabago D, et al. Prolotherapy in primary care practice. Prim Care 2010;37:65-80.

84. Klein RG, et al. A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. J Spinal Disord 1993;6:23-33.

85. Ongley MJ, et al. A new approach to the treatment of chronic low back pain. Lancet 1987;2:143-146.

86. Scarpone M, et al. The efficacy of prolotherapy for lateral epicondylosis: A pilot study. Clin J Sport Med 2008;18:248-254.

87. Maxwell NJ, et al. Sonographically guided intratendinous injection of hyperosmolar dextrose to treat chronic teninosis of the Achilles tendon: A pilot study. Am J Roentgenol 2007;189:W215-W220.

88. Rabago D, et al. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: Results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med 2012;18:408-414.

89. Koltyn KF. Analgesia following exercise: A review. Sports Med 2000;29:85-98.

90. Vuori IM. Dose-response of physical activity and low back pain, osteoarthritis, and osteoporosis. Med Sci Sports Exerc 2001;33(6 Suppl):S551-86;discussion 609-610.

91. Fontaine K, et al. Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: Results of a randomized trial. Arthritis Res Ther 2010;12:R55.

92. Dunn AL, et al. Physical activity dose-response effects on outcomes of depression and anxiety. Med Sci Sports Exerc 2001;33(6 Suppl):S587-S597.

93. Pollock ML, et al. American College of Sports Medicine Position Stand. The recommended quantity of and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Med Sci Sports Exerc 1998;30:975-991.

94. Busch A, et al. Exercise for fibromyalgia: A systematic review. J Rheumatol 2008;35:1130-1144.

95. Thomas E, Blotman F. Aerobic exercise in fibromyalgia: A practical review. Rheumatol Int 2010;30:1143-1150.

96. Wang C, et al. A randomized trial of tai chi for fibromyalgia. N Engl J Med 2010;363:743-754.

97. Carson JW, et al. A pilot randomized controlled trial of Yoga of Awareness program in the management of fibromyalgia. Pain 2010;151:530-539.

98. Williams K, et al. Evaluation of the effectiveness and efficacy of Iyengar yoga therapy on chronic low back pain. Spine 2009;34:2066-2076.

99. Sherman KJ, et al. Comparing yoga, exercise, and a self-care book for chronic low back pain: A randomized, controlled trial. Ann Intern Med 2005;143:849-856.

100. Tekur P, et al. Effect of short-term intensive yoga program on pain, functional disability and spinal flexibility in chronic low back pain: A randomized control study. J Altern Complement Med 2008;14:637-644.

101. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860-867.

102. Centers for Disease Control and Prevention (CDC): Chronic disease prevention and health promotion. Available at: Accessed Oct. 5, 2012.

103. Willett WC. The Mediterranean diet, science and practice. Public Health Nutr 2006;9:105-110.

104. Kohatsu W. The Anti-inflammatory Diet. Ch 86. In: Integrative Medicine. 3rd Edition. Rakel D, ed. Philadelphia: Saunders/Elsevier; 2012.

105. Adam O, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 2002;23:27-36.

106. Mangge H, et al. Diet and rheumatoid arthritis, a review. Scand J Rheumatol 1999;28:201-209.

107. Kaartinen K, et al. Vegan diet alleviates fibromyalgia symptoms. Scand J Rheumatol 2000;29:308-313.

108. Seaman DR. The diet-induced proinflammatory state, a cause of chronic pain and other degenerative diseases. J Manipulative Physiol Ther 2002;25:168-179.

109. Kumar V, et al. Robbins and Cotran Pathologic Basis of Disease. 8th ed. Philadelphia: Saunders; 2009.

110. Fernandes JC, et al. The role of cytokines in osteoarthritis pathophysiology. Biorheology 2002;39:237-246.

111. Fitzgerald CT, Carter LP. Possible role for glutamic acid decarboxylase in fibromyalgia symptoms: A conceptual model for chronic pain. Med Hypotheses 2011;77:409-415.

112. Old Ways: Your guide to good health and well-being. Mediterranean based diet. Available at: Accessed Oct. 5, 2012.

113. Messier SP, et al. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: The Arthritis, Diet, and Activity Promotion Trial. Arthritis Rheum 2004;50:1501-1510.

114. Sierpina V, et al. Mind-body therapies for headache. Am Fam Physician 2007;76:1518-1522.

115. Ernst E. Complementary treatments in rheumatic diseases. Rheum Dis Clin North Am 2008:34:455-467.

116. Kabat-Zinn J. An outpatient program in behavioral medicine for chronic pain patients based on the practice of mindfulness meditation: Theoretical considerations and preliminary results. Gen Hosp Psychiatry 1982;4:33-47.

117. Kabat-Zinn J. The clinical use of mindfulness meditation for the self-regulation of chronic pain. J Behav Med 1985;8:163-190.

118. Hsu MC, et al. Sustained pain reduction through affective self-awareness in fibromyalgia: A randomized controlled trial. J Gen Intern Med 2010;25:1064-1070.

119. UW Family Medicine Mindfulness. Available at: Accessed Oct. 5, 2012.

120. Fortney L, Taylor M. Meditation in medical practice: A review of the evidence and practice. Prim Care 2010;37:81-90.

121. Davis DA, et al. Are reports of childhood abuse related to the experience of chronic pain in adulthood? A meta-analytic review of the literature. Clin J Pain. 2005;21:398-405.

122. Goldberg RT, Goldstein R. A comparison of chronic pain patients and controls on traumatic events in childhood. Disability Rehab 2000;22:756-763.

123. Lampe A, et al. Chronic pain syndromes and their relation to childhood abuse and stressful life events. J Psychosom Res 2003;54:361-367.

124. Draper B, et al. Long-term effects of childhood abuse on the quality of life and health of older people: Results from the Depression and Early Prevention of Suicide in General Practice Project. J Am Geriatr Soc 2008;56:262-271.

125. Sachs-Ericsson N, et al. Childhood abuse, chronic pain, and depression in the National Comorbidity Survey. Child Abuse Negl 2007;31:531-547.

126. Dobie DJ, et al. Posttraumatic stress disorder in female veterans: Association with self-reported health problems and functional impairment. Arch Intern Med 2004;164:394-400.

127. Amir M, et al. Posttraumatic stress disorder, tenderness and fibromyalgia. J Psychosom Res 1997;42:607-613.

128. Sherman JJ, et al. Prevalence and impact of posttraumatic stress disorder-like symptoms on patients with fibromyalgia syndrome. Clin J Pain 2000;16:127-134.

129. Beckham JC, et al. Chronic post-traumatic stress disorder and chronic pain in Vietnam combat veterans. J Psychosom Res 1997;43:379-389.

130. Schmahl C, et al. Neural correlates of antinociception in borderline personality disorder. Arch Gen Psychiatry 2006;63:659-667.

131. Lieberman MD, et al. The neural correlates of placebo effects: A disruption account. Neuroimage 2004;22:447-455.

132. Davidson R, et al. Alterations in brain and immune function produced by mindfulness meditation. Psychosom Med 2003;65:564-570.

133. Linton SJ, Nordin E. A 5-year follow-up evaluation of the health and economic consequences of an early cognitive behavioral intervention for back pain: A randomized, controlled trial. Spine (Phila Pa 1976) 2006;31:853-858.

134. Schubiner H. Emotional Awareness for Pain. Ch 100. In: Integrative Medicine. 3rd ed. Rakel D, ed. Philadelphia: Saunders/Elsevier; 2012.

135. National Institute for Health and Clinical Excellence. Low back pain, early management of persistent low back pain. Issue date May 2009. Available at: Accessed Oct. 5, 2012.

136. Rooks DS, et al. Group exercise, education, and combination self-management in women with fibromyalgia. Arch Intern Med 2007;167:2192-2200.

137. Froud R, et al. Estimating the number needed to treat from continuous outcomes in randomised controlled trials: Methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial. BMC Medical Research Methodology 2009;9:35.

138. Koyama T, et al. The subjective experience of pain: Where expectations become reality. Proc Natl Acad Sci U S A 2005;102:12950-12955.

139. Laerum E, et al. What is "the good back-consultation?" A combined qualitative and quantitative study of chronic low back pain patients' interaction with and perceptions of consultations with specialists. J Rehab Med 2006;38:255-262.

140. Astin JA, Astin AW. An integral approach to medicine. Altern Ther Health Med 2002;8:70-75.

141. Rakel D. The salutogenesis-oriented session: Creating space and time for healing in primary care. Explore 2008;4:42-47.