Mindfulness and Migraine: Is There a Link?

A new replication and extension study finds little to connect the trait of mindfulness with pain in healthy controls, nor is it associated with improvements in headache in people with migraine.

In 2019, researchers at the University of Reading in the United Kingdom reported the first evidence that a natural disposition to be mindful – to focus on the present moment and to react less emotionally to distressing things in one’s environment – was associated with higher pain thresholds, and lower pain catastrophizing, in experimental studies with healthy volunteers.

Focusing on mindfulness as a trait rather than as a trained skill, these investigators also found that mindfulness was associated with a distinct pattern of brain connectivity in a network of brain regions called the default mode network (DMN).

A new study now challenges that line of thinking.

Researchers including lead author Carly Hunt, of Johns Hopkins University School of Medicine in Baltimore, US, now report that they were unable to replicate the findings from the 2019 study. They found few associations between mindfulness, pain, and DMN connectivity in healthy controls, nor did they find such relationships with headache when they extended their investigation to a group of people with migraine.

The new research casts doubt on the earlier findings and suggests that the effects of trait mindfulness on pain and on migraine may be less important, or more complicated, than first thought.

“It is a surprising finding that these relationships are unable to be replicated in healthy controls and do not extend to migraine patients, but that is not uncommon in research and speaks to the importance of replication,” Zev Schuman-Olivier, director of the Center for Mindfulness and Compassion at Harvard Medical School, Boston, US, told MSC in an email.

“It suggests that the findings may not be as consistent or robust as we thought, and that more research in this area may be needed,” added Schuman-Olivier, who was not involved with the current study.

The findings appeared online ahead of print on August 4, 2022, in the Journal of Pain.

A journey to a replication and extension study
Previous studies have shown that mindfulness training can reduce experimental pain, as well as clinical pain. Alterations in the DMN are thought to underlie some of those changes. The DMN is involved in functions such as introspective thought, mind wandering (thoughts not connected to the immediate environment), and rumination.

Despite this, it was unknown whether similar mechanisms come into play in people who are naturally mindful, in the absence of training, and whether the trait of mindfulness could help people cope with pain. That changed with publication of the 2019 study, from first author Richard Harrison and colleagues, which the current replication and extension study would revisit.

Hunt, the first author of the new study, has a longstanding personal interest in the use of mindfulness and mindfulness-based training to help people cope with pain.

“Being exposed to Buddhist philosophical concepts as an undergraduate, particularly nonjudgmental awareness of the present experience and how it relates to the self, was inspiring,” Hunt explained. “This interest took me on a journey into psychology, and the psychology of health in general, before starting a fellowship in pain psychology.”

That journey continued in the new study, which analyzed data from a larger trial, published in 2020, investigating an enhanced mindfulness-based stress reduction program for treatment of episodic migraine, which proved more effective than stress management for headache. Some of the authors on the current replication and extension study, including senior author David Seminowicz, conducted the trial.

That set the stage for the new study, which was a secondary cross-sectional analysis of some of the earlier trial’s data. Hunt was keen to determine if Harrison’s 2019 findings would hold up in a different sample of pain-free individuals, before taking things a step further and testing for associations between mindfulness and headache in a cohort of migraine patients.

“I had previously lived with chronic pain, so being able to look at the extent to which mindfulness could be a protective factor in that context was both scientifically meaningful and personally interesting,” she said.

Harrison was positive when he became aware of Hunt’s efforts to replicate and extend upon his previous work.

“Anyone who works within the realms of neuroscience and psychology is fully aware of the replication crisis, and that it is such a prominent problem within our field,” Harrison explained. “So whenever there’s a paper that comes along and attempts a direct replication, as this paper did, I’m overwhelmingly in support of the idea.”

No replication in pain-free subjects. No extension in people with migraine.
For the new work, the investigators used data from 36 pain-free controls who had never tried mindfulness meditation in the past. They also used data from 98 episodic migraine patients to determine whether the previous findings linking the mindfulness trait to pain thresholds, pain catastrophizing, and DMN connectivity would hold up in a chronic pain cohort. The team assessed connectivity of the DMN using functional magnetic resonance imaging (fMRI) data.

The first key finding from the 2019 Harrison study was that higher self-reported trait mindfulness was associated with higher heat pain thresholds and lower pain catastrophizing. But this result did not hold up in the new study’s cohort of pain-free controls, with the investigators finding no association between mindfulness and heat pain threshold, pain intensity or unpleasantness, or pain catastrophizing.

Nor were there associations between mindfulness and headache frequency, headache severity, or pain catastrophizing in the cohort of episodic migraine patients.

The second key finding from the Harrison study was an association between mindfulness and connectivity of the precuneus with other areas of the brain; the precuneus is a part or “node” of the DMN. In particular, higher mindfulness was associated with higher connectivity between the precuneus and the primary and secondary somatosensory cortices (brain regions that receive and process sensory information). Higher mindfulness was also associated with lower connectivity between the precuneus and the medial prefrontal cortex (which plays a role in numerous cognitive functions).

But Hunt and colleagues observed no associations between mindfulness and precuneus connectivity in either the healthy controls or the migraine cohort. In fact, one of their analyses showed that healthy adults higher in mindfulness had increased connectivity of a different node of the DMN with the cerebellum, which is a region unrelated to pain processing as a function of mindfulness.

The lack of replication was not something Harrison expected.

“I thought the finding we had from 2019 was relatively robust, given the empirical track record of mindfulness and pain that’s been shown relatively steadily for about 20 years,” he said. “I was surprised that none of the findings that I thought would be robust came up.”

How similar were the two studies?
One question that arises when a new study fails to replicate a previous one is whether the methodology of the former is truly similar to that of the latter. If not, it could simply be that methodological differences account for the lack of replication.

So how did the new study fare in that regard?

Both studies recruited, from larger investigations, a cohort of pain-free controls who had never engaged in mindfulness meditation (40 controls in the Harrison paper, and 36 in the Hunt replication and extension), and both used data collected during baseline visits. Similarly, the two studies measured trait mindfulness using the Five-Facet Mindfulness Questionnaire (FFMQ), which is the most commonly used tool for measuring trait mindfulness. So far, so good.

However, there were demographic differences between the study cohorts. Two-thirds of Harrison’s original cohort were male, with an average age of 23 years. In contrast, 90% of participants in the Hunt study were female, with an average age of 30 years.

The age differences could have a significant impact, according to Schuman-Olivier.

“DMN development and connectivity is known to change substantially during adolescence, and while it is assumed to stabilize by the time someone is a young adult, the differences in the FFMQ scores in a younger adult population may reflect differences in ongoing development of this active brain area, allowing for more variability in self-reported mindfulness.”

Schuman-Olivier continued, “There are several neurodevelopmental processes at work during late adolescence and young adulthood that impact DMN connectivity, such as myelination and synaptic pruning, but these processes also impact executive function and cognitive control networks that impact the construction of mindfulness, as measured by the FFMQ.”

The demographic differences between the two studies with regard to sex could have also influenced the associations between mindfulness and pain. This is because there is higher sensitivity to pain, and a greater propensity to report it, among women.

There also were slight variations in how the investigators applied the experimental pain stimuli used to test the effects of trait mindfulness on pain. Harrison and colleagues applied the painful stimuli to the lower right calf of participants, while Hunt and co-authors used the left volar surface of the forearm (the part of the forearm on the same side as the palm of the hand). Previous evidence suggests that sensitivity to noxious stimuli varies across different body sites, so this could have been an important difference between the two studies.

“The tip of the filing cabinet problem”
Despite the lack of replication across the two studies, Hunt and Harrison agree on the importance of this type of work, and hope other researchers aren’t discouraged by the results. To the contrary, they feel the findings open up multiple avenues of research to explore.

“Ongoing research to further understand how mindfulness training works is one future direction. Perhaps untrained and trained mindfulness are different pieces [of the puzzle], and future research could help us understand what those differences are,” Hunt said.

“What could be happening,” Hunt continued, “is that the mindfulness we get through purposeful training is more meaningful than the naturally occurring level of mindfulness that we have. I think this could be a positive from a patient perspective. Being able to train in mindfulness and get those benefits is something that anyone can do – it’s not because of how much mindfulness you are born with, so to say.”

“I think this may represent the tip of the filing cabinet problem,” Harrison said of the new study. “Perhaps there are other authors out there who perhaps didn’t take as bold a step as Hunt and colleagues did to publish this null finding and say, ‘Hang on, we actually haven’t found evidence that you are all publishing.’”

Harrison continued, “It makes me wonder about some of the data we’ve got in our filing cabinet – the strange things where we couldn’t replicate something that was relatively robust, and we inherently criticized ourselves. Maybe we need to publish more of those studies where we didn’t find evidence that fits into the narrative.”

Lincoln Tracy is a researcher and freelance writer from Melbourne, Australia. You can follow him on Twitter @lincolntracy.

Reference
Is mindfulness associated with lower pain reactivity and connectivity of the default mode network? A replication and extension study in healthy and episodic migraine participants.
Hunt et al.
J Pain. 2022 Aug 4. Online ahead of print.