Abstract
Background
Mindfulness refers to a host of procedures that have been practiced for centuries, but only recently have begun to be applied to varied pain conditions, with the most recent being headache.
Methods
We reviewed research that incorporated components of mindfulness for treating pain, with a more in depth focus on headache disorders. We also examined literature that has closely studied potential physiological processes in the brain that might mediate the effects of mindfulness. We report as well preliminary findings of our ongoing trial comparing mindfulness alone to pharmacological treatment alone for treating chronic migraine accompanied by medication overuse.
Results
Although research remains in its infancy, the initial findings support the utility of varied mindfulness approaches for enhancing usual care for headache management. Our preliminary findings suggest mindfulness by itself may produce effects comparable to that of medication alone for patients with chronic migraine and medication overuse.
Conclusions
Much work remains to more fully document the role and long term value of mindfulness for specific headache types. Areas in need of further investigation are discussed.
Do not rely on tradition, scripture, authority or philosophy. Only when you see for yourself that a practice leads to suffering or to wellbeing then you should either reject or accept it (1).
Introduction
Mindfulness has a long history, with its roots being grounded in ancient Hinduism, Daoism, and Buddhism. Central to the many forms of mindfulness is the intentional, non-judging mental awareness on the present, which is based on the idea that mental activity has a significant role in influencing physiological processes in the brain. Mindfulness strives to promote an attitude of curiosity, openness and acceptance, allowing one to develop a non-judgmental attitude towards internal sensations – including thoughts, emotions and pain – to engage in making intentional choices and to enhance self-efficacy. It seeks to enable people to focus on moment-by-moment experiences, interrupting the pattern of continuous partial attention that characterizes much of our daily lives. Its more recent emergence as a therapeutic intervention in behavioral medicine parallels the rising interest in cognitive behavior therapy, meditation, acceptance-based interventions (acceptance and commitment therapy or ACT), and positive psychology, approaches designed to help reduce psychological distress and promote personal control (2–6). Put more simply in the context of headache (7), most prior (and current) psychologically-based approaches focus on challenging, disputing, resolving, and/or avoiding stimuli that give rise to, exacerbate, or serve to maintain sources of headache and associated distress. In marked contrast, mindfulness-based approaches emphasize developing cognitive distance from and learning how to willingly face expectations that cannot or need not be changed. Hence, the goal centers on learning how to accept life's uncontrollable events.
Langer and colleagues (8) were among the first to show the value of a mindful cognitive reappraisal intervention for reducing stress and improving wellbeing in patients about to undergo surgery (as well as exploring the potential benefits of mindfulness in other areas, such as aging, health, and creativity). This work represented perhaps one of the first transformations of eastern Buddhist concepts after their introduction into western scientific perspectives and culture and into contemporary psychology. A few years later, Kabat-Zinn (9) reviewed more in depth how the Buddhist concept of mindfulness came to be integrated into western culture and healthcare, and presented his preliminary findings with varied pain conditions. Soon after, Walsh and Shapiro (10) further discussed the integration of meditative disciplines and Western psychology, while Brown and colleagues (11) addressed the role of mindfulness practice in improving mental and physical health, enhancing behavioral regulation, and increasing interpersonal skills, and suggested mechanisms by which mindfulness exerted its effects.
In preparing this manuscript we searched the term “Mindfulness” on PubMed and >3,500 records were retrieved, with the clear majority of them (≈75%) being published in the last five or so years. In this narrative review, we have endeavored to focus on those articles of most scientific relevance in the field of pain science and in particular headache science.
Mindfulness practice
Many of the modern applications of mindfulness to medicine, and pain in particular, can be attributed to the seminal work of Jon Kabat-Zinn and colleagues (9,12,13). Some form of meditation plays a key role in the various mindfulness techniques researched to date. Baer (14) prepared an overview of current mindfulness techniques typically applied in clinical settings, conducted a meta-analysis of approaches employed in 20 available studies, and reported four as being the most popular mindfulness-based treatment approaches: mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT), dialectical behavioral therapy (DBT), and acceptance and commitment therapy (ACT). These approaches have been successfully implemented to enhance the ability to regulate emotion in adults experiencing many different conditions, and also in children (15).
Among the different protocols, MBSR and a close variant – MBCT – have garnered the most attention to date for management of various forms of recurrent pain. We begin with a brief overview of the many pain conditions investigated thus far, then comprehensively review applications with headache, followed by discussion of possible mediators of mindfulness and an assessment of the present state of knowledge, as well as limitations of mindfulness applications with headache. We conclude with a presentation of preliminary data from our ongoing study that attempts to address some of the identified limitations.
Mindfulness and chronic pain
Veehof and colleagues have conducted two extensive meta-analytic reviews of acceptance and mindfulness-based therapies, with the most recent occuring in 2016. The first (16) examined all studies published by the end of 2008, with the authors concluding these forms of therapies (MBSR, MBCT, and ACT) produced, on average, small effects, which were similar in magnitude to those obtained by cognitive behavioral approaches (17), heretofore one of the most supported non-pharmacological approaches. Only a few years later, the research base had increased by such a sizeable amount, and with a concurrent increase in study quality, that a follow-up meta-analysis was warranted (18). Of the 87 studies that had appeared in the interim and that were considered as possibly appropriate, 20 fulfilled their rigorous inclusion criteria. The eight randomized controlled trials identified in their prior review were combined with the 20 more recent studies, leading to an available pool of 28 studies, with 25 having sufficient data (a total of 1,285 patients in all) to be included in the main sets of analyses. Of these 25 studies, 11 chiefly utilized MBSR-based approaches, nine were ACT-based, two were MBCT-based, and one employed a combination of MBCT and MBSR. The two remaining studies implemented variants of the preceding approaches (Mindfulness-based Pain Management or Four Step Mindfulness-Based Therapy). The treatment programs reviewed ranged in length from four to 12 weeks, with session lengths lasting from 1.0 to 2.5 hours (with the modal treatment being delivered in a group format over eight weeks). Nine studies focused on chronic pain – unspecified, seven targeted fibromyalgia, six included site-specific pain, two addressed rheumatoid arthritis, and one addressed musculoskeletal pain. It is of particular note here that only three of the studies included headache patients (chronic tension-type headache, primary headache, and chronic headache, with the latter mentioned in a study consisting of an unpublished dissertation).
Numerous measures were examined, at different follow-up intervals, comparing varied treatments and comparison/control conditions. Here we summarize key findings of direct interest. At post-treatment small effects were found for measures assessing pain intensity, depression, quality of life, and disability, with moderate effects surfacing for pain interference and anxiety. Follow-up data available for two to six months after treatment was completed revealed further gains in effectiveness for most measures: effect sizes were now moderate for depression and quality of life, with the moderate post-treatment effects for anxiety enduring (data addressing disability were too limited for reporting). The effect size for pain interference had increased to a large value, with the effect size for pain intensity remaining small. This pattern of findings is consistent with the stated focus of mindfulness-based treatments, where direct control and reduction of pain is not the primary aim. Rather, the chief aim is to minimize the focus on pain and avoid “fighting” it. Although reduction of pain intensity is not the primary goal of such approaches, it has been hypothesized and some research support exists for the notion that increased acceptance of one's pain condition can alter brain mechanisms that impact the experience of pain (see subsequent section for further discussion of this). Finally, an exhaustive review conducted by panelists of the Italian Consensus Conference on Pain in Neurorehabilitation (19) accorded mindfulness treatments the highest level of evidence for chronic pain syndromes with heterogeneous physiopathology (Grade A).
Mindfulness as applied to headaches
Sun, Kuo, and Chiu (20) were perhaps the first investigators to draw attention to the potential value of mindfulness training for individuals experiencing headache. Their case study report emanates from working with a 30-year-old male, four years prior to publication, who had enrolled in a class on mindfulness meditation (walking and then sitting). Their astute observations and scientific acumen yielded novel insights that warrant special mention. The first session of sitting meditation induced an intense headache, one that was more painful than any prior episode and was accompanied by sensations and in locations never before experienced. When instructed by his experienced trainer merely to observe all bodily phenomena, the headache eventually subsided. Continued practice of techniques being taught in the course nevertheless led to repeated cycles of headache onset, with him once again aborting headaches by narrowing his approach to observation alone. When exploring his history in greater depth, these Taiwanese investigations learned the individual developed a keen interest in Qigong at age 11, practicing it regularly. Within a couple of years he began to experience debilitating headaches, much like those he experienced in his class many years later. For the following eight years each practice of Qigong resulted in an intense headache, often lasting for days. Around the age of 20 (about 10 years later), he discontinued all practice of Qigong, with the headaches subsiding.
Further skillful probing by Sun et al., with the helpful analysis of the individual who had now become a physician and was able to help rule out underlying physical causes and provide more firm estimates of pain levels (typically rated from 6–8 on a 10-point visual analog scale), led to the realization that the individual in question was utilizing a form of Qigong that involved not only concentrating on the flow of energy within one's body, but active attempts to guide the energy flow. He subsequently learned when working with a master-instructor to alter his practice by ceasing attempts to regulate energy flow and shifting to observation alone. Although the physician was not seeking treatment for pain when he enrolled in the course, his fortuitous encounter yielded most insightful accidental findings, best summed up in a direct quote from him. While observing the change in my headache, I understood how physical sensations could be modified and controlled by mental means. When I feared a headache and tried to avoid it, I was actually bound more tightly to the pain. But when I put aside my anxious feelings, my pain and discomfort grew less. This experience helped me to understand my body more deeply, and to sense its innate ability to adjust and recover; and it gave me a stronger feeling of controlling my body. (p. 539)
Initial investigations
The earliest applications of a form of mindfulness specifically designed to evaluate its utility in headache management derived from spiritually-inspired varieties of meditation, several of which were first examined with college-aged volunteers who were assigned to “spiritual meditation,” “secular meditation,” or relaxation (21). All participants received two sessions, spaced two weeks apart, and were instructed to engage in home practice of their assigned technique for 20 minutes each day during the intervening period. Various psychological, spiritual, and adherence measures were administered, and all participants were subjected to a cold pressor task at study's end. Individuals who were exposed to spiritual mediation revealed consistent and greater improvements, as well as increased pain tolerance, when compared to all remaining conditions. These encouraging results led these authors to conduct a second study (22) that replicated not only two of the prior conditions (spiritual meditation and relaxation), but extended their design to include a more fine-grained analysis of secular meditation (comparing “internally focused” secular meditation to “externally focused” meditation), and tested all procedures with individuals diagnosed as experiencing vascular headache (migraine and migraine mixed with tension headache; IHS classification, 2nd edition), verified with the ID Migraine screener (23), a valid and reliable three-item screening instrument for migraine headaches in primary care, with the analysis consisting of questions on disability, nausea, and photophobia. Time devoted to practice of techniques was doubled to four weeks. At the end of treatment, spiritual meditation resulted in the greatest improvements when compared to the other three conditions for nearly all measures, including decreased headache frequency. Although encouraging, this study was limited in that it included a non-treatment seeking largely student population, baseline headache measures relied on retrospective recall for the prior month, and followup occurred only at the end of treatment.
The most recent treatment investigation emanating from this group (24) included headache patients diagnosed as before, who were then randomized to the four prior treatment conditions, each lasting one month, with an increased focus on headache frequency, severity, and analgesic consumption. This time, daily diaries were maintained only during the one-month study period. Once again, spiritual meditation led to the largest reductions in headache frequency, which surpassed those for the remaining comparison conditions. While all four treatments promoted decreased consumption of medication, the reductions were greatest for spiritual meditation. No differences were found with respect to headache severity. Similar limitations were present: daily diaries were maintained only during the one-month study period, patients were largely non-treatment seeking college students, and medication use was minimal (those who remained in the study took only non-prescription analgesics; none of them took abortive or prophylactic agents).
A final study by this group (25), perhaps best construed as an analog, merits brief mention. Here, 27 migraineurs (diagnosed by the ID Migraine criteria with concurrence by primary care providers and reporting 2–10 migraines per month) were offered a 20-minute session of Buddhist Loving Kindness meditation (delivered in small groups). Ratings of pain and “emotional tension” (0 to 10), obtained before and immediately after meditation, revealed reductions of 33% and 43%, respectively. The authors conclude this approach may well serve as an “effective, quick, and portable” intervention in and of itself, as well as a means to provide relief until acute medications can take effect. These claims await validation.
Applications of MBSR and closely-related approaches
Another wave of mindfulness investigations has all drawn essentially upon Kabat-Zinn's more structured MBSR course, adapted for headache patients (versus chronic pain patients), a program that typically includes eight weekly two-hour group sessions, plus a concluding one day “mindfulness retreat” of about six hours' duration. Various procedures are included to promote acquisition of a “non-judgmental moment-to-moment awareness”, such as mindful eating, breathing, sitting and walking meditation, body scanning, and yoga (or mindful movement). Participants share experiences throughout and are provided with information about stress and ways to relieve stress, minimize stress reactivity, and develop more positive and proactive ways of responding via the application of learned techniques. Patients are continually reminded to bring their attention back to more natural patterns of breathing. Finally, they are taught how to incorporate mindfulness into their daily routines (such as when brushing teeth, showering, and completing routine chores). All of this is designed to enable patients to become more flexible in applying mindfulness day by day.
Wells and colleagues (26) conducted one of the first randomized controlled trials with episodic migraineurs (19 in all; ICHD-2), wherein patients were assigned to either usual care (chiefly pharmacological prophylaxis) or usual care combined with MSBR. Data collected at the latest time point (one month following completion of treatment), revealed few significant differences between the two conditions (perhaps due in part to limited statistical power). The addition of MBSR did not increment effects for their primary measure of outcome – headache frequency, but it did lead to greater improvements in several of their secondary measures – headache duration, HIT-6, and a measure of mindfulness; other measures fell short of achieving significance (MIDAS, self-efficacy, MSQL, depression, state-trait anxiety, and perceived stress). The authors reported that patients showed excellent adherence to the therapeutic program and daily meditation practice, which is notable given the high time demands placed upon them.
Bakhshani et al. (27) conducted a similar analysis of the addition of MBSR to standard care in treating chronic forms of headache, which included those diagnosed primarily as chronic migraine and tension-type headache (diagnosed by IHS criteria; 40 in all). Patients were again assigned on a random basis to pharmacotherapy alone or pharmacotherapy + MBSR. These authors do not appear to have included the full-day workshop as more commonly done with this approach, and also added a number of elements not routinely included in MBSR (identifying negative automatic thoughts and feelings including anger and emotion with pain, concepts of acceptance, additional breathing exercises, daily recording of pleasant and unpleasant events as well as behavioral activation – both commonly employed in protocols focusing on depression, seeing/hearing exercises, poem reading, and relapse prevention). Here the addition of MBSR led to increased improvements in pain intensity and quality of life (SF-36) (with significant effects for both summary scales and six of the eight subscales) at immediate post-treatment. In addition to the very limited follow-up, the authors did not report data they appeared to collect with respect to headache frequency and duration, and their sample is insufficiently described, so it is difficult to determine if and how many patients were solely migraine, tension-type, or combined, and whether they assessed for medication overuse (a particularly important consideration when dealing with chronic forms of headache).
The remaining investigation with a chief focus on MBSR targeted tension-type headache (but not distinguishing episodic or chronic) and assessed impact on perceived stress and mental health, as well as headache activity (28). The 66 patients were randomized to therapy as usual (TAU) or TAU plus MBSR (apparently absent inclusion of the all-day concluding workshop) and followed for three months, the longest follow-up in a series of this type to date. At their brief follow-up, patients receiving the combined condition reported levels of improvement in stress, anxiety, and general mental health (assessed by the Brief Symptom Inventory and the Perceived Stress Scale) significantly greater than those for routine treatment alone. Interestingly, these authors report monitoring pain severity levels, but only for a limited number of patients (n = 5), and did not share even these values. Regrettably, this otherwise well done investigation has limited value for headache practitioners and researchers absent any headache outcome data.
An investigation by Day, Thorn, Ward, Rubin, Hickman, Scogin, and Kilgo (29) is mentioned along with the three above studies as these authors employed a similar type of systematic program, one being influenced and infused by principles of cognitive behavior therapy – by now a well-established treatment for headaches (30,31), resulting in a treatment package termed Mindfulness-Based Cognitive Therapy (MBCT). The cognitive therapeutic aspects selected for inclusion were designed to augment adaptive thought processes based on principles of acceptance, while aiding patients in reducing maladaptive thoughts, such as catastrophizing, which is known to exacerbate headache and pain. In other research, MBCT has been shown to be of value for addressing cognitive aspects of depression, anxiety, and insomnia. In fact, their program drew heavily from a version of MBCT previously developed and successfully tested for patients experiencing depression (32). In this investigation, which focused not only on efficacy but also feasibility, tolerability, and acceptability, 36 adults with primary headaches (86% migraineurs, but also a mixture of tension-type, cluster, and “other” unspecified types of headache, with many having a variety of comorbid other pain conditions) were randomized to MBCT or delayed treatment (DT), all already receiving routine medical care in a headache center (which was not well characterized in the report). Selection of measures was guided by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) (33). Evaluation of immediate post-treatment data revealed the following: no significant differences in headache outcomes or medication intake between conditions; however, the addition of MBCT did lead to significant improvements in reported self-efficacy and pain acceptance. Findings were similar when comparing results from both completer and intent-to-treat analyses, as well as when those initially assigned to DT were subsequently treated (a notable feature, as this is not often performed or, if performed, not reported). Finally, relatively high rates of dropout (25%) occurred. In a secondary analysis, these authors (34) addressed the features of responders, defined as those patients achieving at least 50% improvement in pain intensity and/or pain interference, versus non-responders. Pain-related issues, i.e., improvement in pain intensity and interference, reduced catastrophizing, and higher pain acceptance, were identified as the key factors underlying response to MBCT treatment.
The final study mentioned in this section (35) integrated aspects of MBSR with MBCT, with the resultant treatment, termed Mindfulness-based Therapy (MBT), being delivered over a briefer period (two-hour group classes were delivered twice per week over a three-week period). Patients who met ICHD-2 criteria for chronic tension-type headache and were free from medication overuse were randomly assigned to MBT or maintained on a waiting list. Treatment focused on management of headache pain, contributing stress factors, and associated psychosocial consequences. Three forms of meditation were additionally taught: body scanning, formal sitting, and a three-minute breathing space (focusing on internal experiences, breath, and the body as a whole). Group discussions centered on applying techniques in everyday life and documenting reactions to pleasant as well as unpleasant events. Patients were urged to practice for 30 minutes each day. Of the 58 patients admitted into the study, 42 completed it. The sample consisted of 29 patients in each group (23 completers in the mindfulness group and 19 in the control group). Headache diaries maintained for two weeks before and after treatment revealed significant reductions as a function of treatment, but only for headache frequency; no significant changes were found for diary the measures obtained from the Depression Anxiety Stress Scales-21 (depression, anxiety, and stress). Although statistically significant, the reduction in headache frequency was marginal, decreasing from a mean value of 11.04 prior to treatment to 9.37 post-treatment (15% reduction).
Applications of Acceptance and Commitment Therapy (ACT)
Dindo et al. (36) were among the first to adapt principles of ACT for headache, focusing their initial attempt on comorbid depression and migraine (the latter being screened by the ID Migraine). Forty-five patients were assigned to either a one-day workshop, where the chief focus was on ACT, which included education about migraine (with this condition termed ACT-ED), or to a waiting list (where they were temporarily left to pursue treatment on their own). The workshop lasted about five hours and focused on three main topics:
Migraine education (pathology, triggers, risk factors for chronification, treatments (unspecified), medication overuse headache, and lifestyle contributors). Acceptance, which included instruction in alternative ways to manage distressing thoughts, feelings, and pain sensations – learning to recognize and implement cognitive distance from dysfunctional thoughts and to face situations that were unresolvable. Behavior change training, where patients were instructed how to identify ineffective behavioral patterns and habits, explore and establish life and health-related goals, and effectively engage in actions to achieve their desired goals.
ACT is among the treatments identified by the American Psychological Association as having moderate to strong research support for varied disorders (depression, chronic pain, mixed anxiety, OCD, and psychosis) (http://www.div12.org?PsychologicalTreatments/treatments.html). Information collected at three months revealed greater improvements in symptoms of depression, general functioning (WHO Disability Assessment Schedule II and the SF-36), and disability (HDI) relative to those on the waiting list. This “proof of concept” investigation, unfortunately, did not report findings for any measures of headache. A follow-up study employing the same basic design (one-day ACT-ED workshop versus TAU) did include daily diary recordings of headache parameters prior to and for three months following intervention, as well as measures of disability (37). Although participants receiving ACT-ED treatment revealed significant reductions in headache occurrence, headache severity, and consumption of acute medication over time, these changes were not significantly different from those receiving standard care at the three-month follow-up (none of the condition by time period interaction effects were significant, calling into question the appropriateness of conducting separate tests of significance for each condition alone for each measure across time). Similar findings were reported for disruptions to leisure and work activities.
The remaining investigation of an ACT-based treatment (drawing upon the work of Vowles et al. (38)) was conducted with 30 females, from an initial pool of 80, who were seeking outpatient treatment for chronic forms of headache (migraine and tension-type; ICHD-2) at a headache specialty clinic (39). One half were randomly assigned to medical treatment as usual, with the others receiving eight weekly sessions of ACT, each delivered in a group format of about 90 minutes' duration, combined with medical treatment. At post-treatment, ACT combined with standard care led to greater reductions in disability (MIDAS) and affective distress (Trait Anxiety) (two of three primary measures of outcome) than standard care alone. No differences were found for the sensory component of pain (assessed by the McGill Pain Questionnaire – Short Form), the remaining primary outcome measure. Greater reductions were also found for the affective dimension of pain (derived from the McGill), which served as a secondary measure of outcome. Sixty-three percent of patients were diagnosed as experiencing chronic tension-type headache, with the remainder (37%) being diagnosed with chronic migraine without aura. The sample sizes were too small to examine response by headache type.
Applications with adolescents
Hesse and colleagues (40) reported the only study we could find that applied MBSR to adolescents experiencing recurrent headaches, i.e. four or more headaches per month occurring over at least three months. Treatment was administered during eight two-hour sessions delivered weekly. The primary outcome was the feasibility and safety of the intervention, while change in headache-related disability/impact, anxiety, depression, quality of life and change in headache frequency and severity were secondary outcomes. The intervention appeared feasible and safe, and patients showed reduced depression after treatment. No change occurred with headache-related disability and QoL, and no information was reported with regard to headache frequency.
Possible mechanisms of action
How mindfulness exerts its effects remains controversial, and this is likely due in part to the specificity of the different health conditions for which it has been applied. Mechanisms of action need to be considered from different perspectives: the psychological relation that a person has with his/her experience of pain on one hand, and concurrent modification of brain area functioning and inflammatory process activity on the other, that may occur as patients become more proficient at applying their skills. Mindfulness, it is proposed, likely helps to improve the mental and general health status of patients, particularly among those enduring long-standing painful conditions. Viewed from this perspective, mindfulness practice induces development of the “observer-self”, setting the stage for the patient to observe his/her thoughts and feelings in a non-reactive and non-judgmental way and learn to notice thoughts without necessarily acting on or being controlled by them. Second, mindfulness may help alter sensations and emotions associated with a patient's condition, which may in turn serve to increase self-efficacy and self-esteem. These aspects may help promote an internal locus of control with a concomitant decrease in clinical signs and symptoms, thus leading to improvements in quality of life (QoL) (41–44). Again, mindfulness is designed to promote a sense of self that is greater than one's thoughts, feelings, and bodily sensations, such as pain. When successfully applied, it helps one to engage in valued action and to modulate attention and emotional reactions to pain, which play an important role in promoting pain persistence and chronification. Opening oneself to pain rather than fighting pain serves to reduce the mind's tendency toward avoidance and anxiety, which can further exacerbate the experience of pain and its interference with daily activities (45,46).
Studies conducted over the past 10 + years have begun to examine these notions by focusing on potential physiological mechanisms of mindfulness, beginning perhaps with the work of Davidson and others (13). In this investigation, individuals who were randomly assigned to an eight-week MBSR program (à la Kabat-Zinn) were found to have increases in immune function (in terms of increases in antibody titers to influenza vaccine) when compared to their untreated counterparts. Further, the magnitude of increase in left-sided activation, measured by brain electrical activity before and after the program, predicted the magnitude of antibody titer rise to the vaccine. Salomons and Kucyi's (47) review concludes that meditation may affect the functioning of cerebral structures known to be involved in the integrative representations of pain and its affective components. Their brief review provides further support for the view that meditation may reduce pain through measurable neurological post-intervention changes, including the thickening of cortical regions associated with pain processing, reduced activation in the amygdala, hippocampus, and emotional/evaluative regions of the prefrontal cortex, as well as increased activation in the mid-cingulate cortex, thalamus and insula. Grant and colleagues (48), who applied functional magnetic resonance imaging to study the cerebral circuits involved in pain processes in those who regularly practiced meditation versus those who did not, confirmed that during the presence of pain, experienced practitioners had reduced activation in the amygdala, hippocampus, and emotional/evaluative regions of the prefrontal cortex, as well as an increased activation in the midcingulate cortex and insula. These results provide further evidence that mindfulness enables one to increase attention to present experience while decreasing emotional responses. Gard and colleagues (49) similarly found that a reduction in “unpleasantness” produced by mindfulness was associated with decreased activation in the lateral prefrontal cortex.
Through mindfulness, pain relief is possible, and this is speculated to occur as an indirect result of learned abilities to relinquish cognitive control, which leads to a concurrent increase of sensory processes in the brain (50). Zeidan and colleagues (51) found that meditation induced a reduction in pain-related activation of the contralateral primary somatosensory cortex, and that reductions in pain intensity ratings were associated with an increased activity in the anterior cingulated cortex and anterior insula (the areas involved in the cognitive regulation of the nociceptive processes). They also noted a reduction in pain unpleasantness associated with orbito-frontal cortex activation and with thalamic deactivation. These fMRI data indicate that mindfulness meditation involves multiple brain mechanisms that alter the construction of the subjective pain experience from afferent information. In yet another fMRI investigation, Lutz and colleagues (52) found that expert meditators reported a pain intensity level that was similar to that for novices, but with decreased unpleasantness. This clinical aspect was associated with enhanced activity in the dorsal anterior insula and the anterior mid-cingulate, and with reduced baseline activity before pain in the same regions as well as in the amygdala.
Taken as a whole, neuroimaging data suggest that the regular experience of meditation through mindfulness may induce important changes in the pain network, with a down-regulation of anticipatory representation of aversive events and an increase in the recruitment of attentional resources during the experience of pain, which is associated with quicker neural habituation (53).
Most recently, researchers have returned their focus to inflammation. Creswell and colleagues (54) examined whether mindfulness meditation could alter the default mode network resting state functional connectivity and if this was related to immune function. “Stressed” job-seeking unemployed community adults were randomized to either a three-day intensive residential mindfulness meditation or relaxation training program. All job-seekers underwent resting-state brain scans and provided blood samples that were assayed for circulating interleukin-6 levels (IL-6), a biomarker of systemic inflammation, prior to participation. Mindfulness meditation, but not relaxation, produced a significant modification in the default-mode-network; it specifically increased posterior cingulate cortex resting-state functional connectivity, which was accompanied by a significant improvement in IL-6 levels, an increase re-confirmed at four months' follow up. Lengacher and colleagues (55) similarly found, in their pilot investigation conducted with advanced-stage cancer patients (and their caregivers), that MBSR led to measureable improvements in psychological symptoms (stress and anxiety), physical symptoms, and stress markers (lower levels of salivary cortisol up to three weeks and lower salivary IL-6 up to six weeks). Caregivers reported minor benefits for psychological symptoms, lower salivary cortisol up to three weeks and lower salivary IL-6 up to one week, supporting the value of MBSR for both patients and caregivers.
Sharon et al. (56) examined whether mindfulness meditation-induced analgesia involved endogenous opioids. Fifteen healthy experienced mindfulness meditators were asked to rate perceived pain and unpleasantness in response to a cold stimulus before and after a mindfulness meditation session. Participants were randomized to receive either intravenous Naloxone or saline, after which they meditated again, and rated the same stimulus. Pain and unpleasantness scores were significantly reduced after mindfulness meditation and after saline, but not after Naloxone. The study provides initial evidence that meditation can indeed impact endogenous opioid pathways, mediating its analgesic effect and growing resilient with increasing practice to external suggestion. However, a more recent investigation examining the potential mediating effects of endogenous opioids (57), employing somewhat similar methodology, was unsupportive of this notion. One potential explanation for these diverse findings may be that they are due in part to the experience level of participants, the type of mindfulness meditation implemented, and the amount of practice that intervened between pre- and post-testing. For example, Sharon et al. focused on experienced meditators who participated in a far greater number of sessions than the meditative-naïve participants of Zeidan et al. (57) (four total sessions administered close in time, with no outside practice permitted). Secondary, correlational analyses conducted by Sharon et al. confirmed a significant relation between level of experience and degree of meditation analgesia. Further research is clearly warranted with respect to this topic.
Interim conclusions
Overview of included studies.
Notes. MBSR, mindfulness-based stress reduction; MBCT, mindfulness-based cognitive therapy; ACT, acceptance and commitment therapy; RCT, Randomised Controlled Trial; TTH, Tension-Type Headache; ICHD-2, International Classification of Headache Disorders, 2nd version; NPDH, new persistent daily headache; HA, headache; NA, not available; QoL, quality of life; NRS, numerical rating scale. We omitted inclusion of Wachholtz and Pargament (2005) (21) as their study did not include patients with headaches and Hesse et al. (2015) (40), as it was the sole investigation to focus on adolescents.
Bold font identifies the group receiving mindfulness-based treatment and, in the instance where multiple versions of mindfulness were administered, the condition that revealed the greatest improvement.
Finally, researchers need to give greater thought to the selection of process and both primary and secondary measures of outcome, owing to the different goals of mindfulness-based treatments. We have known for some time that pain is multi-dimensional. Beecher (60), over half a century ago, proposed that the pain experience consists of at least two interacting components (and others have speculated even more dimensions): sensory, which includes attributes like location, intensity, frequency, and quality; and reactive, which concerns one's emotional reaction, fears and concerns about the meaning of the pain, and abilities to cope. The daily headache diary, which has become the gold standard for assessing primary head pain outcome, provides information bearing chiefly on the sensory dimension (61). Pharmacological and behavioral trial guidelines both specify that frequency measures of headache should serve as the primary outcome in clinical trials (62,63). Nonetheless, it is important to remember that the main goal of mindfulness and related treatments is to impact the reactive or affective dimension of pain and not the sensory dimension per se. The latter is suspected to be a likely outcome, but, again, it is not the chief target. Measures of headache impact, disability, and emotionality are more in line with the goals of mindfulness-based treatments, but more precise measures are in need of development in order to more fully elucidate the impact and mechanisms underlying mindfulness treatments.
Preliminary findings
It is against this backdrop that we set out to conduct a trial of a more circumscribed mindfulness-based treatment, administered to a well-characterized and relatively homogenous group of particularly difficult-to-treat headache patients (chronic migraine complicated by medication overuse), comparing this treatment by itself to medication alone, and collecting longer-term follow-up data. As this investigation is being conducted in a clinic setting that has a large catchment area and is exploratory in nature, patients were permitted to choose between the conditions of interest to us. Thus, we view our ongoing study more as an “effectiveness” trial (versus an efficacy trial; Nash et al. (64)).
Patients in this ongoing trial have a history of chronic migraine for a minimum of 10 years and concurrent overuse of triptans and NSAIDS for a minimum of five years (meeting the criteria for IHS-III, beta version, 2013). All first participated in a structured outpatient medication withdrawal program (65,66), and once this was completed they were encouraged to increase physical activity and perform aerobic exercises to the extent possible for 45 minutes twice per week, maintain adequate hydration, and consume three daily meals on a regular basis (emphasizing the importance of breakfast). Prior to discharge, patients were given the option to receive appropriate prophylactic medication alone (N = 22) (chosen on the basis of their history and medical comorbidities, as done in routine care) or mindfulness training alone (N = 22). In the medical prophylaxis alone condition, five patients received valproate, eight botulinum toxin, five pizotifen, one amitriptyline, two received a combination of beta blockers and amitriptyline, and one was given beta blockers and valproate.
Mindfulness training was delivered in small groups that met for approximately 30 minutes each week, for a total of six sessions. During treatment, patients were instructed to assume a relaxed position, with eyes closed, and focus on their breathing and the present in order to promote enhanced awareness of their current mind and body sensations. When intruding thoughts occurred, they were instructed to return their focus on breathing and body awareness, all the while maintaining a non-judgmental attitude. They were asked to engage in home practice of the learned techniques for seven minutes per day. Regardless of condition assignment, patients were encouraged to restrict the use of acute medications to “very disabling” headaches, operationally defined as a rating of eight or greater on a 0–10 point scale. A variety of measures are being collected, and the distributions of scores for the MIDAS and HIT-6 reveal similar levels of headache impact and disability at the start of the trial. Data collection is ongoing and will continue for a minimum of 12 months.
When this article was prepared, complete data sets were available for 21 patients in the mindfulness group and 20 in the pharmacotherapy group at the six-month follow-up assessment. Reductions in headache frequency, comparing pretreatment to six-month follow-up, were similar for both conditions (44% for mindfulness vs. 43% for medication); however, the percentage of patients with evidence of significant clinical improvement (defined as a reduction ≥50%) was greater for those receiving mindfulness training alone (48% vs. 30%). Consumption of acute medications revealed greater improvement for those patients assigned to mindfulness, irrespective of how improvement is calculated: 49% vs. 37% for overall group reductions and 48% vs. 30% for the percentage of individual patients who were significantly improved, for mindfulness and pharmacotherapy, respectively.
Concluding remarks
Available data support the notion that meditation and variants of mindfulness training impact the activity of brain areas connected to neuromodulation and control of pain. Although limited, accruing evidence, including our preliminary findings, suggests promise for mindfulness-based approaches in the treatment of recurrent headache (a conclusion similarly reached in an earlier review including a portion of the studies examined here (67)), perhaps particularly so for more complicated forms of headache. Whether and the extent to which this promise is fulfilled awaits further research.
Article highlights
Various mindfulness-based approaches, specifically Spiritual Meditation, Mindfulness-Based Stress Reduction, Mindfulness-Based Cognitive Therapy, and Acceptance and Commitment Therapy, show promise of enhancing existing treatments for varied headache types. Our preliminary data suggest that mindfulness alone may be comparable to pharmacological treatment alone for chronic migraine accompanied by medication overuse. Emerging research is providing some initial support for the theory that engaging in mindfulness can impact brain pain pathways, inflammation, and endogenous opioids. Although promising, a number of research issues need further attention, some of which include identifying optimal components and delivery schedules, examining effects with specific headache types, conducting more rigorous controlled trials that assess the durability of effects over extended time periods, and reconsidering the measures best suited for examining treatment process, as well as primary and secondary outcomes.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.