Studies · 22 papers and trials

The science behind the new model of pain

Papers and trials behind the idea that pain is shaped by the nervous system, not only by tissue damage: how it is defined, what scans do and do not show, how emotion and expectation change pain, and how it can be treated.

How to read this list

Not every paper carries the same weight. The tag on each row tells you what kind of paper it is: original research, a review, or an expert consensus. Dashed tags show where a paper stands.

RCT
A randomized controlled trial. People are randomly assigned to a treatment or a comparison group.
RCT follow-up
Later results from the same randomized trial.
Pilot trial
A small trial run first to test feasibility. Its results are preliminary.
Secondary analysis
A new look at data from a trial that has already been run.
Experiment
A lab study where people are put in a situation, or given a suggestion, and report what they feel. It shows what is possible, not how common it is.
Observational study
Researchers measure and compare what people already have or experience. No treatment is assigned.
Imaging study
Brain scans compared across people or over time.
Review
A summary of what many studies found.
Expert consensus
An agreed position from an expert panel. It defines terms or criteria and reports no new results.
Registered
A trial listed in a public registry, with no results yet.
Preprint
A report not yet checked by independent experts. Shown next to the paper type.

Papers and trials

22 papers and trials in 6 groups

Defining the model

4 papers

How nociplastic pain is defined and recognized.

  • 2011 · PainWoolf

    Central sensitization: implications for the diagnosis and treatment of pain

    Lays out how amplified signaling in the central nervous system can produce pain hypersensitivity, and why it matters for diagnosis and treatment.

    Review
  • 2019 · PainTreede et al.

    Chronic pain as a symptom or a disease: the IASP classification for ICD-11

    Introduced chronic primary pain, recognizing chronic pain as a condition in its own right and not only a symptom of something else.

    Expert consensus
  • 2021 · PainKosek et al.

    Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system

    Proposed clinical criteria and a grading system for judging whether pain is nociplastic. Still being tested and debated.

    Expert consensus
  • 2021 · The LancetFitzcharles et al.

    Nociplastic pain: towards an understanding of prevalent pain conditions

    Reviews nociplastic pain as a third mechanism beside nociceptive and neuropathic pain, and the common conditions it may underlie.

    Review

How pain changes the nervous system

2 papers

What brain imaging shows as pain becomes chronic.

  • 2012 · Nature NeuroscienceBaliki et al.

    Corticostriatal functional connectivity predicts transition to chronic back pain

    In people with recent back pain, brain connectivity measured early helped predict who went on to develop chronic pain.

    Imaging study
  • 2013 · BrainHashmi et al.

    Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits

    As back pain became chronic, the brain activity tied to it shifted from circuits for sensing pain toward circuits for emotion.

    Imaging study

Pain Reprocessing Therapy

6 papers

Trials of Pain Reprocessing Therapy.

  • 2022 · JAMA PsychiatryAshar et al., the Boulder trial

    Pain Reprocessing Therapy vs placebo and usual care for chronic back pain

    66% of the therapy group were pain free or nearly so, vs 20% on placebo and 10% on usual care, with gains largely maintained at one year.

    RCT
  • 2023 · JAMA Network OpenAshar et al.

    Reattribution to mind-brain processes and recovery from chronic back pain

    Secondary analysis of the Boulder trial. Recovery was linked to people coming to see their pain as driven by mind-brain processes rather than tissue damage.

    Secondary analysis
  • 2025 · JAMA PsychiatryAshar et al.

    Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain: 5-Year Follow-Up of a Randomized Clinical Trial

    Five-year follow-up of the Boulder trial (113 of 151 participants). 55% of the PRT group were pain free or nearly so, vs 26% on placebo and 36% on usual care.

    RCT follow-up
  • 2025 · Reg Anesth Pain MedSturgeon et al.

    Brief pain reprocessing therapy for fibromyalgia: a feasibility, acceptability, and preliminary efficacy pilot

    A short form of PRT in three one-on-one remote sessions, in 35 people with fibromyalgia, with no comparison group. 94% completed the program, and pain fell among those who did. A randomized trial is needed to confirm it.

    Pilot trial
  • 2026 · J Psychosom ResSit et al.

    Pain Reprocessing Therapy in chronic widespread pain

    Feasible in primary care (n = 53). 30% vs 12% reached a 2 point reduction in pain severity; trends favored the therapy on every secondary outcome.

    Pilot trial
  • In progress · NCT07287072University of Oslo

    PRIME-PRT: Pain Reprocessing Therapy in primary care

    Norwegian primary care trial of PRT in adults aged 18 to 70 with chronic pain and no clear physical cause, probably nociplastic. Recruitment has closed and results are not yet published.

    Registered

Risk and context

1 paper

Factors linked with pain becoming chronic.

  • 2026 · medRxiv

    Pain Amplifier Loop Framework, umbrella review

    Sleep disturbance, catastrophizing, metabolic inflammation and opioid exposure were each associated with chronification or treatment failure. Observational, so causation is not established.

    ReviewPreprint

What scans show

3 papers

Scan findings are common in people with no pain at all. That does not make scans useless, and it does not mean pain is imagined. It simply means a finding on its own does not always explain pain.

  • 2009 · SpineTakatalo et al.

    Prevalence of degenerative imaging findings in lumbar magnetic resonance imaging among young adults

    MRI of 558 Finnish 21-year-olds found at least one degenerated disc in almost half and a bulging disc in a quarter. Herniations and Modic changes were rare.

    Observational study
  • 2015 · AJNRBrinjikji et al.

    Systematic literature review of imaging features of spinal degeneration in asymptomatic populations

    Pooled studies of people with no back pain. Disc degeneration appeared in 37% of 20-year-olds and 96% of 80-year-olds, so many findings are likely part of normal aging.

    Review
  • 2026 · JAMA Internal MedicineIbounig et al.

    Incidental rotator cuff abnormalities on magnetic resonance imaging

    Both shoulders of 602 adults aged 41 to 76 were scanned. Abnormalities showed up in 96% of pain-free shoulders and 98% of painful ones.

    Observational study

Emotions, learning and expectation

6 papers

Pain is real however it is generated. These studies show that meaning, expectation and emotion change how much pain people feel.

  • 1956 · JAMABeecher

    Relationship of significance of wound to pain experienced

    Soldiers with severe wounds asked for pain medication far less often than civilian patients (32% vs 83%). The size of the wound did not reliably predict pain. A historical report, not a controlled experiment.

    Observational study
  • 1991 · PainBayer et al.

    Situational and psychophysiological factors in psychologically induced pain

    People connected to a sham stimulator and told it might cause a headache reported pain half the time, against 25% of those not connected. Reports rose as the dummy settings were turned up.

    Experiment
  • 2001 · Int J Legal MedCastro et al.

    No stress, no whiplash? Prevalence of "whiplash" symptoms following exposure to a placebo rear-end collision

    51 volunteers were exposed to a fake rear-end collision with no real impact. About 20% reported whiplash-type symptoms within 3 days and 5 still did at 4 weeks.

    Experiment
  • 2004 · NeuroImageDerbyshire et al.

    Cerebral activation during hypnotically induced and imagined pain

    Hypnotic suggestion of painful heat, with nothing applied to the skin, activated thalamus, cingulate, insula, prefrontal and parietal regions, as real heat pain does.

    Imaging study
  • 2011 · PNASKross et al.

    Social rejection shares somatosensory representations with physical pain

    People who had recently been through an unwanted break-up looked at a photo of their ex. Areas involved in the sensory side of physical pain became active.

    Imaging study
  • 2017 · Nature CommunicationsWoo et al.

    Quantifying cerebral contributions to pain beyond nociception

    A brain pattern built from fMRI of 183 people predicts reported pain better than stimulus strength alone does. It also reflects the effect of expectation and perceived control. A research signature, not a diagnostic test.

    Imaging study

Figures come from published abstracts, trial registries and the University of Colorado Boulder summary of the trial. Preprints are not peer reviewed. Older and small experiments are included for context and carry less weight. This page is informational and not medical advice.