New research explores the behaviors and brain regions associated with avoidance of pain, including the role of pain coping.
Avoiding pain in order to minimize harm and injury is critical for survival. Although the ways people avoid pain are constantly revised and updated after the experience of a painful event, these behaviors can become disrupted when pain is repeated and inescapable.
Studies in animals have linked a brain region called the periaqueductal gray (PAG) to behavioral and other changes that take place during pain avoidance. However, it is unknown if the PAG and related regions have a similar role in pain avoidance in people.
Now, new research led by Wiebke Gandhi, University of Reading, UK, reveals that episodic migraine patients show reduced pain avoidance behavior and reduced brain activation after a previously unsuccessful avoidance attempt. Contrary to the authors’ original hypothesis, a different area of the brain, called the posterior parietal cortex, seemed to play the most important role here, rather than the PAG.
The investigators also found that, after unsuccessful pain avoidance, subjects’ feelings of helplessness about their migraine was correlated with larger decreases in activation of brain areas linked to motor behavior, attention, and memory.
“This study is a new way of looking at avoidance behavior,” said Kai Karos, a pain scientist at KU Leuven in Belgium who studies pain-related fear and avoidance behavior but was not involved in the current research.
“Usually we focus on avoidance behavior as a whole, but these researchers look at the development of avoidance behavior over time based on previous experience,” continued Karos. “We know from experimental models that fear avoidance is an important part of the development and maintenance of pain. This paper is interesting, as it takes a different approach to how we think about avoidance behavior in the development of pain.”
The study appeared in the June 2022 edition of the journal PAIN.
Setting up an experiment to study pain avoidance
First author Gandhi has long been interested in exploring the interactions between pain and the information people receive about pain. Her research during graduate school focused on pain avoidance, and the interactions between pain and reward (where avoiding pain can be thought of as positive reinforcement).
When considering the role of motivation in pain avoidance, Gandhi was curious as to how people with long-term experience of being unable to control their pain would respond to immediate feedback about pain avoidance (either successful or unsuccessful avoidance). This led her to consider people with migraine in particular.
“At first, I thought, migraine is a classic model for learned helplessness. Eventually, if you can’t have control over your pain, it would be expected that people become helpless,” she said.
“But as I looked further into the literature, I found that many migraine patients don’t feel helpless at all. Instead, they are proud of themselves that they’re starting to manage living with the pain. That’s the part I thought was so interesting – this wide spread of people who manage their pain really well, whereas others can’t deal with the fact that they are so often in pain.”
To learn more about the pain avoidance behavior of people with migraine and how the brain responds, Gandhi and colleagues recruited 32 study participants, including 26 women (with an average age of 27 years), 15 of whom had episodic migraine, and 17 healthy control subjects. The researchers used an adapted version of the incentive delay task, a tool commonly used to study motivated behavior, while participants lay in an MRI scanner. In this context, the participant’s goal was to avoid receiving a painful stimulus and receive a non-painful one instead.
For each trial in the pain avoidance task, participants were first shown one of three words on a computer screen: “safe,” “easy,” or “difficult.” After this prompt, a target cue would appear in the middle of the screen. Participants were instructed to press a response button as quickly as they could when they saw the target cue appear.
If participants pressed the button in the required timeframe during the “easy” and “difficult” trials, then they received a non-painful electric shock. If participants didn’t respond quickly enough, they received a painful electric shock. Participants had to respond more quickly in the “difficult” condition to avoid getting shocked. In the “safe” trials, participants received a non-painful shock if they pressed the button, regardless of how long that took.
“When we analyzed the data, we wanted to see, on the next trial, how participants were dealing with the most recent feedback from the previous trial,” Gandhi explained. “We compared trials where people were previously successful at avoiding the painful stimulus to trials where they were unsuccessful.”
Self-reported measures of depression and helplessness were also collected from participants, to explore associations between these factors and response speed and brain activity during the pain avoidance task.
Unsuccessful pain avoidance alters behavior…
First, Gandhi and colleagues explored how a lack of success in avoiding pain on the preceding trial altered response speed on the next trial. Participants with migraine were slower to respond in “difficult” trials if they had been unable to avoid the painful electric shock in the previous trial, compared to when they avoided the pain.
Furthermore, migraine patients’ self-reported helplessness scores were associated with the decrease in response speed following an unsuccessful trial – the higher the helplessness score, the greater the reduction in response speed. These results imply that the coping style of patients is an important part of pain avoidance behavior.
“What I thought was interesting is that when we plotted the individual data, we saw a huge overlay between the healthy controls and migraine patients. Many migraine patients behaved very, very similar to the healthy controls,” Gandhi said.
“We found that, as anticipated, it’s really those who can’t deal with their clinical pain and feel very helpless about it who are really affected by the previous negative feedback, and then reduce the response speed to quite some degree. But I think it’s important to see that it’s not every patient. It really came down to coping ability.”
These behavioral results were somewhat surprising to Karos.
“To me, the most surprising finding from a clinical standpoint is that if study subjects had an unsuccessful trial, they were less likely to succeed on the next trial, especially in the patients with episodic migraine. What we typically see in chronic pain is too much avoidance behavior, rather than too little. I would have expected a learning effect where patients would try harder next time, especially so in pain-free participants, where they amplify their avoidance behavior.”
Surprise aside, the findings certainly piqued Karos’ interest.
“What I would have liked to see is if they had looked at the data on a trial-by-trial basis, rather than simply grouping trials together. I would have liked to see the development of their performance across the whole task, to see how people’s performance changes throughout.”
… and changes the brain, too.
When it came to the brain imaging data, Gandhi and colleagues focused on the preparatory phase – the period where participants were presented with the cue indicating how difficult the upcoming trial would be, but before the target cue was shown and they were required to respond via button press. Similar to the behavioral experiments, the authors were interested in comparing results after successful versus unsuccessful pain avoidance on the previous trial, only this time they looked at brain activity.
In all participants after an unsuccessful trial, several brain regions showed decreased activation during the preparatory phase of the subsequent trial, including the bilateral posterior parietal cortex, the anterior cingulate cortex, the insula, and the premotor cortex. These regions are part of a “preparatory matrix” involved with alertness, preparing or executing movements, and cognitive control.
Further, participants without migraine showed a greater increase in right parietal cortex activation with increasing task difficulty after an unsuccessful preceding trial, compared to participants with migraine.
And, consistent with the behavioral experiments, higher helplessness scores in subjects with migraine were associated with less activation, in regions including the posterior parietal cortex, after unsuccessful pain avoidance, compared to subjects without migraine.
“The imaging results nicely supported what we saw on a behavioral level,” Gandhi concluded. “When we looked at the trials when people were previously unsuccessful, activity of most of the involved brain areas was reduced, which explains the reduction in response speed. We saw it was specifically the right parietal cortex that migraine patients couldn’t recruit to the same extent as healthy controls.”
She continued, “Again, these results indicate that it’s not that the between-group differences are being driven merely by the fact that people have chronic pain. It’s the interaction between this experience and their ability to deal with it.”
Focusing on helplessness – and an important caveat
To Gandhi, taking a more individualized approach to how patients are taught to think about their pain could yield benefits.
“The perception of helplessness comes down to the perception of control over the pain condition. I think this study highlights the need to focus on perceived controllability, and to try and train that,” she said.
Gandhi has formed a collaboration with Nazanin Derakhshan, Birkbeck University of London, UK, to further explore the effects of helplessness. Derakhshan and colleagues have recently used a targeted training program to increase attention to external task-relevant stimuli to pull attention away from internal input (often referred to as self-screening), which can decrease anxiety in cancer pain patients.
“There might be a way to adopt the mechanisms they’ve used in cancer pain patients to work on attention in people with migraine,” Gandhi explained. “I can see something similar in the current study, where participants just experienced pain and so there is a focus on internal self-screening. The pain – the internal stimulus – captures the patient’s attention to such a degree that it seems hard to redirect the attentional focus back on external task-relevant stimuli again.
“Redirecting the focus back to external stimuli could be a potential way to target helplessness in a clinical sense,” Gandhi added.
While the current results add to the understanding of pain avoidance and how avoidance behaviors are reflected by changes in brain activity, Karos highlighted the need for ample caution when interpreting the data.
“As this is a cross-sectional study, it’s not possible to insinuate causal relationships – which the paper does at several points – especially between brain processes and behavior. I think you must clearly distinguish between different types of pain as well. The task used hard-to-avoid pain, which is different than unavoidable pain. It would be interesting to explore the difference between unavoidable pain, hard-to-avoid pain, and easily avoidable pain, as this could have completely different implications for avoidance behavior,” Karos said.
“Furthermore, the study was underpowered, which adds to the need to interpret these findings with caution.”
Lincoln Tracy is a research fellow and freelance writer from Melbourne, Australia. You can follow him on Twitter @lincolntracy.
Neural and behavioral correlates of human pain avoidance in participants with and without episodic migraine. Gandhi et al. PAIN. 2022 Jun 1;163(6):1023-34.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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