Key Research:
Mind-body Medicine
Research into Pain and Threat Learning
Understanding pain as threat or challenge: predictive roles of resilience, attachment, and sensory sensitivity
Lajaunie et al. Pain Medicine. 2025
Abstract available here. Full text here.
In this recent study, 278 participants with chronic pain were assessed for factors that may result in them perceiving pain as either a threat or a challenge. Higher pain intensity, general sensitivity, anxious attachment and lower resilience all resulted in participants being more likely to reflexively perceive and respond to pain as a threat. Threat-based interpretations are linked to greater distress and poorer pain outcomes.
The authors conclude that exploring pre-existing psychological factors may guide clinicians in applying appropriate pain interventions that best meet their patients’ needs. They also highlight that the results align with the delivery of treatments that focus on re-appraisal of pain sensations such as Pain Reprocessing Therapy.
The interaction between stress and chronic pain through the lens of threat learning
Timmers et al. Neurosci Biobehav Rev. 2019
This scientific review pools research, determining that ‘threat learning’ is a major contributing factor to chronic pain. It explores threat-related neurological and biological ‘pathways’ in the brain and body that can result in pain and those that drive ‘threat’ in relation to pain.
The authors conclude that ‘threat learning’ (our brain determining threat around pain) is a central mechanism and contributor to pain persistence. This ‘threat learning’ mediates the relationship between stress and chronic pain. The authors conclude that integration of this knowledge can potentially help guide future clinical practice.
Research into Pain and Emotions
A systematic review of associations between emotion regulation characteristics and inflammation
Moriarity, D. et al. Neuroscience & Bio-behavioral Reviews. Volume 15105162.
2023.
Available here.
This systematic review of 38 papers (2816 initially identified) explored the associations between a variety of emotion regulation traits and inflammation. Of those final papers, 28 (74%) found that (a) poor emotion regulation is associated with higher inflammation and/or (b) strong emotion regulation skills are associated with lower inflammation.
The authors conclude that incorporating and acknowledging the link between emotional regulation and inflammation might result in more comprehensive treatment plans that provide flexibility for patient needs and preferences.
Amygdala physiology in pain
Neugebauer V. et al. Handb Behav Neurosci. 2020
Available here.
This research paper explored the role of the amygdala (area of the brain that processes fear-based emotion and is linked with memory) in pain. The authors emphasise that amygdala activity may be a predetermining factor in the persistence of pain, highlighting differences in people’s response and experience of pain. The research demonstrates that increased stress signals in ‘functional pain conditions’ (those without injury) cause nerve cells in the amygdala to become more active. It is also stressed that greater activity in the nerve cells (neurons) involving the amygdala can result in increased activity in nerve cells sending information from the body.
The authors highlight how the pre-frontal control centres (the conscious thinking centres) of the brain simultaneously become less active. The result is an overactivity within the fear-related emotional brain areas, and an underactivity of the areas of the brain areas involved in emotional regulation and decision making.
The authors conclude that the combination of these changes to neural circuits within brain regions likely play a key role in driving pain behaviours and pain persistence.
Research into Predictive Factors and Traits Relating to Pain Persistence
Perfectionism, self-compassion, and general self-efficacy between those with and without chronic pain
Ditchburn, G.J. et al. Psychology & Health. 2025
The authors completed two research studies exploring the link between people with persistent pain and personality. Three traits were focused upon: perfectionism, self-compassion and general self-efficacy (an individual's belief in their personal capacity to act in the ways necessary to reach specific goals).
Perfectionism was then split into two categories – self-oriented (the internal drive to meet very high standards for oneself) and socially prescribed (to meet the perceived expectations of others). Self-compassion was gauged by how kindly people treat themselves in difficult moments. Self-efficacy measured the extent to which participants believed they could achieve goals and handle challenges.
237 participants with chronic pain and 237 without pain completed an online survey. Participants with chronic pain had significantly higher levels of socially prescribed perfectionism (an internal drive to meet the perceived expectations of others), and lower levels of self-compassion than those without pain.
In the second study, involving 294 individuals with chronic pain, and 278 without, individuals with chronic pain reported significantly higher levels of perfectionism and lower levels of self-compassion and self-efficacy than pain-free individuals. Perfectionism was higher in those with low self-compassion scores.
Self-compassion was described by the authors as a protective buffer that strengthens inner resilience and may have an impact upon experiences of chronic pain.
Corticostriatal circuits in the transition to chronic back pain: The predictive role of reward learning
Löffler M, et al. Cell Rep Med.
Available here.
This research study explored the connectivity between two areas of the brain to predict the development of chronic back pain. Specifically, the extent to which conditioning/predictive learning within the pathways of two brain regions may predict the transition to and maintenance of chronic pain. These two brain areas of research were the Ventral Medial Pre-frontal Cortex (VMPFC) - implicated in processing risk, fear and emotional regulation - and the Nucleus Accumbens (NAC), implicated in motivation, reward learning, attention and reinforcement learning. Together, these regions highlight a maladaptive response, where the brain starts reinforcing pain-related expectations, behaviours, and emotional responses.
The authors conclude that chronic pain may be driven by learning reinforcement mechanisms, similar to habit formation. They suggest that early prediction of chronic pain risk may be identifiable through observing brain ‘biomarkers’. Notably, they discuss how these findings support treatment that could target reward processing and learning to affect the sensation, as opposed to directing treatment directly to the pain sensation.
Psychophysiologic symptom relief therapy for chronic back pain: a pilot randomized controlled trial.
Donnino, MW, et al. PAIN Reports. 2021.
Available here.
This small-scale pilot study compared a mind-body therapy (psychophysiologic symptom relief therapy - PSRT) with mindfulness-based stress-reduction (MBSR) for participants with chronic non-specific lower back pain. PSRT addressed underlying emotional stressors and psychological contributors to persistent pain (including underlying stressful conflicts and underlying subconscious emotions), as well as unconsciously learned pain responses and fear-avoidant behaviours. Treatment strategies in the first 4 weeks of PSRT included pain education especially focussed on emotional and psychological contributors, desensitization, and emotional expression therapies.
Compared to MBSR and usual care, PSRT helped more patients achieve substantial reductions (75%) in back pain disability.
At 26 weeks, 63.6% of the PSRT arm reported being pain free (0/10 pain) compared with 25.0% and 16.7% in MBSR and usual care arms, respectively.
The authors conclude that psychophysiologic symptom relief therapy is a practical and potentially highly beneficial treatment for patients with nonspecific back pain.
Research into Pain Reprocessing Therapy
Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients with Chronic Back Pain: A Randomized Clinical Trial
Ashar Y.K., Gordon A., Schubiner H., et. al. JAMA Psychiatry 2022
Available here.
This randomised clinical trial aimed to evaluate whether a psychological treatment (pain reprocessing therapy [PRT]), which aims to shift patients' beliefs about the causes of pain, could provide substantial and long-lasting pain relief from persistent back pain. The study also aimed to investigate the scientific mechanism contributing to changes in symptoms.
PRT was compared with an open-label placebo treatment (a subcutaneous saline injection into the participants’ backs) and with routine, usual care.
Participants randomly designated to PRT participated in 1 telehealth session with a physician and 8 psychological treatment sessions over 4 weeks.
Of the 151 total participants, 33 of 50 participants (66%) within the PRT group were pain-free or nearly pain-free following treatment (reporting a pain intensity score of 0 or 1 out of 10), compared with 10 of 51 participants (20%) randomized to placebo and 5 of 50 participants (10%) within the usual care group.
Treatment effects were maintained at 1-year follow-up. Longitudinal fMRI showed:
(1) reduced responses to evoked back pain in the anterior midcingulate and the anterior prefrontal cortex for PRT vs placebo (these two brain areas are heavily involved in how we evaluate, decide, and act in response to pain or uncertainty. They evaluate how much the pain/sensation matters).
(2) reduced responses in the anterior insula for PRT vs usual care (the anterior insula is responsible for interpreting information from the body, turning bodily signals and discomfort into conscious emotions and meaning, and contributes to pain anticipation).
(3) increased resting connectivity from the anterior prefrontal cortex and the anterior insula to the primary somatosensory cortex (S1) for PRT vs both control groups. Greater connectivity from the anterior pre-frontal cortex to S1 suggests cognitive control over sensory processing and reinterpretation of sensation. Essentially the brain is saying “I understand this sensation, and it’s not threatening.” The connectivity from the anterior insula to S1 suggests improved accuracy of bodily awareness and more accurate recognition of the body. Essentially the brain is saying “I feel this, but it’s ok”.
(4) increased connectivity from the anterior midcingulate to the precuneus for PRT vs usual care (this suggests pain sensations are now being processed in a reflective rather than a reactive manner. The immediate defensive reaction to pain is lowered. This increased connectivity suggests there is reduced urgency and focus upon pain, thus leading to a reduction in pain).
"I don't have chronic back pain anymore": Patient Experiences in Pain Reprocessing Therapy for Chronic Back Pain
Tankha H. et al. Journal of Pain. 2023.
Available here.
A sample of 32 adults with chronic back pain who received Pain Reprocessing Therapy (PRT) completed interviews about their treatment experiences. The analyses identified 3 major themes reflecting participants' understanding of how PRT led to pain relief:
1) reappraisal to reduce fear of pain, relating to pain as a helpful indicator of how protective their brain is being, overcoming pain-related fear and avoidance, and reconceptualizing pain as a "sensation"
2) the link between pain, emotions, and stress, which included gaining insight into these connections and resolving difficult emotions
3) social connections, which included patient-therapist connection, therapist belief in the treatment model and seeing others’ recovery.
Reattribution to Mind-Brain Processes and Recovery from Chronic Back Pain: A Secondary Analysis of a Randomized Clinical Trial
Ashar Y.K., et. al. JAMA Network Open 2023
Available here.
This analysis explored whether people changing how they think about the origins of their pain was associated with pain relief. 151 people with chronic lower back pain were interviewed regarding their top 3 perceived causes of their pain.
Participants were interviewed both pre and post both pain reprocessing therapy (PRT) intervention and pre and post placebo saline injection and usual care. Before PRT treatment, most participants attributed their back pain to biomechanical or physical causes (e.g. injury, activity, posture). After PRT, there was a large increase in the number of participants whose descriptions referred to mind- or brain-related causes (e.g. stress, brain processes).
Increases in mind-/brain-related attributions to pain were associated with significant reductions in reported pain intensity after treatment. A separate analysis showed that changes in how one understands the cause of their pain persisting partially explains the long-term pain reduction in pain seen with PRT.
Research into Pain and Emotional Awareness & Expression Therapy
Emotional awareness and expression therapy, cognitive behavioural therapy, and education for fibromyalgia: a cluster-randomized controlled trial.
Lumley MA, et al. Pain. 2017.
230 adults with fibromyalgia were randomly assigned to one of three treatment groups: Emotional Awareness and Expression Therapy (EAET), Cognitive Behavioural Therapy (CBT), or fibromyalgia education. Treatments consisted of 8 x 90-minute sessions. Patient-reported outcomes were assessed at baseline, post-treatment, and 6-month follow-up.
Participants who engaged in EAET had significantly better outcomes than fibromyalgia education with regards to overall symptoms, widespread pain, physical functioning, cognitive dysfunction, anxiety, depression, positive emotional state and life satisfaction.
Compared with CBT, EAET led to significantly lower fibromyalgia symptoms and a higher percentage of patients achieving 50% pain reduction (22.5% vs 8.3%).
The authors concluded that EAET was viewed as credible, had high participation rates, and had as few negative outcomes as both FM education and the field’s standard psychological treatment for fibromyalgia, CBT.
Emotional Awareness and Expression Therapy vs Cognitive Behavioural Therapy for Chronic Pain in Older Veterans: A Randomized Clinical Trial.
Yarns BC, et al. JAMA Network Open. 2024
This 2-arm randomized clinical trial was conducted from May 16, 2019, to September 14, 2023. Participants were a group of 126 racially and ethnically diverse veterans aged 60 to 95 years with at least 3 months of musculoskeletal pain.
Participants were randomly assigned to partake either in Emotional Awareness and Expression Therapy (EAET) or Cognitive Behavioural Therapy (CBT). Each therapy provided one 90-minute individual session followed by eight x 90-minute group sessions.
Among 126 randomized participants, mean age 71.9, 111 (88%) completed post-reatment, and 104 (82%) completed the 6-month follow-up.
EAET was superior to CBT for the primary outcome of reduction in pain severity at post-treatment. Pain reduction was significant between the two interventions (63% EAET vs 17% CBT). At post-treatment, EAET also demonstrated greater improvements than CBT within most outcomes—anxiety, depression, life satisfaction, PTSD symptoms, patient’s overall perceived change, and overall satisfaction with their health.
The researchers concluded that incorporating emotional processing into current pain treatment could improve outcomes and reduce chronic pain burden.
Emotional Awareness and Expression Therapy Achieves Greater Pain Reduction than Cognitive Behavioural Therapy in Older Adults with Chronic Musculoskeletal Pain: A Preliminary Randomized Comparison Trial.
Yarns BC, Lumley MA et al. Pain Med. 2020.
In this randomised comparison trial, 53 veterans with chronic musculoskeletal pain were randomised to either Emotional Awareness and Expression Therapy (EAET) or Cognitive Behavioural Therapy (CBT). Each treatment was delivered as one 90-minute individual session and eight 90-minute group sessions.
At post-treatment, 41.7% of EAET patients had >30% pain reduction, one-third had >50%, and 12.5% had >70%. Only one patient in the CBT group achieved at least 30% pain reduction. Secondary outcomes demonstrated small to medium-effect size advantages of EAET over CBT, although only post-treatment anxiety reached statistical significance.
The research concludes that targeting emotional awareness, expression, and unresolved emotional conflict may be particularly effective for chronic pain in older populations. Results suggest that therapies addressing central and emotional mechanisms of pain can yield greater pain relief than standard management approaches.