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Research Post-Surgical & Complex Pain
Why Does Pain Linger After Surgery for Some People? A 2,285-Person NIH Study Has Finished Recruiting
The Acute to Chronic Pain Signatures programme followed people for a year after knee replacement or chest surgery, collecting blood, brain scans and function tests. Its goal is to find signatures that predict who will develop lasting pain — a test it has not yet produced.
This article is general health information written by our editors from the sources listed below. It has not yet been medically reviewed — see our medical review policy. It is not advice for your situation.
Two people have the same knee replaced by the same surgeon. A year later, one has forgotten about it; the other is still in pain. Why? That question — why acute pain becomes chronic for some people and not others — sits behind one of the largest pain studies ever run, and in October 2026 the National Institutes of Health reported that it had finished recruiting.
What the researchers are doing
The Acute to Chronic Pain Signatures programme, known as A2CPS and funded through the NIH Common Fund, recruited people who were about to have either a total knee replacement or thoracic surgery. Before the operation and for up to 12 months afterwards, researchers collected blood samples, brain imaging, functional tests and the participants’ own reports of pain and recovery. On 8 October 2026 NIH announced that the consortium had recruited 2,285 participants and performed more than 3,000 brain-imaging sessions, which it describes as the ninth-largest brain-imaging study to date and the largest ever focused on pain.
The idea is to compare people whose pain resolved with people whose pain persisted, looking for differences — in biology, brain activity, psychology or function — that were present early on. If such “signatures” can be identified, they could help researchers develop treatments that prevent the transition and help clinicians identify people who need extra support after surgery.
What is known so far
The October update is about completing data collection, not about results. NIH notes that nearly one in five people worldwide live with chronic pain and that for most people acute pain after injury or surgery resolves as the injury heals, while for others it lingers for years. The programme was also profiled in the journal PAIN’s 50th-anniversary issue in 2025, which described A2CPS as a new model for collaborative, data-driven pain research.
Why it matters in everyday life
Persistent pain after surgery is common enough that most people know someone affected, yet it is poorly understood and hard to predict. For patients, a reliable early warning would change the conversation before an operation: who should have closer follow-up, more rehabilitation support or a different pain plan from day one. For the field, a shared dataset of this size is a resource that many research groups can use for years.
What this does not establish
- No prediction test exists yet. Recruitment is complete, but the analyses that might identify signatures are still to come, and any candidate marker would then need validation in other groups of patients.
- The study involves two kinds of surgery — knee replacement and thoracic surgery. Findings may not transfer to other operations or to pain that starts without surgery.
- Even a validated signature would show risk, not destiny. It could not tell an individual patient that they will, or will not, develop chronic pain.
Questions you might discuss with your clinician
- Before surgery: what is the plan for managing my pain afterwards, and what should I do if it does not improve as expected?
- Which factors in my own history — existing pain, anxiety, sleep, previous surgery — might affect my recovery, and can they be addressed beforehand?
- At what point after surgery should persistent pain be assessed by a pain specialist?
For pain that continues after an operation, the treatments SEVA Healthcare lists are described on our Post-Surgical & Complex Pain page.
Frequently asked questions
What is the A2CPS study?
The Acute to Chronic Pain Signatures program, funded through the NIH Common Fund, recruited people about to have a total knee replacement or thoracic surgery. Researchers collected blood samples, brain imaging, functional tests and participants' own reports of pain before surgery and for up to 12 months afterwards.
Has the study found a way to predict who will have lasting pain after surgery?
Not yet. The October 2026 update is about completing data collection, not results, and any candidate marker would still need validation in other groups of patients.
Will the findings apply to every type of surgery?
The study involves only knee replacement and thoracic surgery. Findings may not transfer to other operations or to pain that starts without surgery.
What could I ask my clinician before surgery?
You might ask what the plan is for managing pain afterwards and what to do if it does not improve as expected. You could also ask which factors in your own history, such as existing pain, anxiety, sleep or previous surgery, might affect recovery and when persistent pain should be assessed by a pain specialist.
Sources
- Cracking the Code of Chronic Pain: A2CPS Program Updates — NIH Common Fund, 2026-10-08
- Wager TD, Sutherland SP, Lindquist MA, Sluka KA, The A2CPS Consortium. Accelerating discovery in pain science: the Acute to Chronic Pain Signatures program — PAIN 166(11S):S95–S98, 2025-11-01
- Study DOI: 10.1097/j.pain.0000000000003674
This article is sponsored content by SEVA Healthcare and is for general information only — it is not medical or legal advice. Treatment options depend on an individual evaluation, and results vary from person to person. In an emergency, call 911. Spotted an error? See our corrections policy.
