For Researchers

Study Goals


What is the overall goal of the study?

The overall goal of the Acute to Chronic Pain Signatures (A2CPS) Program is to identify putative biomarkers (individual or biosignature combinations) that predict susceptibility or resilience to the development of chronic pain after an acute pain-inducing event.

Why is the study important?

The United States faces a crisis due to the high prevalence of chronic pain and associated opioid use disorder and overdose deaths. More than 25 million adults in the U.S. report experiencing pain every day. A major challenge in pain care is the lack of evidence-based best practices to prevent chronic pain from occurring after an acute pain episode. For most people, acute pain resolves over time as the injury or trauma heals. In many people, however, acute pain from injury, surgery, or disease persists well beyond the initial insult—sometimes throughout life—and is often intractable. Chronic pain may persist beyond the typical window for healing due to changes in the peripheral and central nervous systems. However, the mechanisms driving the transition from acute to chronic pain states are poorly understood.

What is A2CPS trying to accomplish?

The ability to predict which patients are more likely to be susceptible versus resilient to the development of chronic pain is a crucial step towards the development of personalized prevention and treatment strategies. Toward this end, the overall goal of the Acute to Chronic Pain Signatures (A2CPS) Program is to identify putative biomarkers (individual or biosignature combinations) that predict susceptibility or resilience to the development of chronic pain after an acute pain-inducing event. Determining pre-injury/surgery factors, and factors during the acute-phase response to injury/surgery, could provide the basis for prophylactic interventions to prevent the onset of chronic pain as well as contribute to our understanding of the dynamic processes that underly the transition from acute to chronic pain. Furthermore, if any of the predictive biomarkers identified through this program play a mechanistic role in the development of chronic pain, then the molecules, pathways, and/or brain circuits identified could serve as new potential therapeutic targets for reversing chronic pain or increasing patients’ resilience.

What are biomarkers?

For the purposes of the A2CPS consortium, biomarkers are defined as measures that can (a) be assessed for an individual person; (b) assessed from one type of data collected with one technology (e.g., a blood sample analysis, an MRI image, a GWAS chip, or self-reported psychological inventories); and/or (c) relate to a pathway or construct of theoretical interest (e.g., pro-inflammatory cytokine expression or threat avoidance). While some definitions of biomarkers include only physiological measures, we also include behavioral measures that may serve similar prognostic functions. Biomarkers can be identified as individual variables (e.g., a single genetic Single Nucleotide Polymorphism [SNP]) or could be based on profiles across individual variables that are measured simultaneously with the same technology (e.g. polygenic risk score) or an early trajectory measure (e.g. change in pain or anxiety over an acute period).Linking biomarkers across levels of analysis—including physiology, -omics, and behavior—is also a priority, as each level may help explain observations at other levels and create a more comprehensive understanding of the transition to chronic pain, i.e. a biosignature. Measures at different levels of analysis also have complementary strengths and weaknesses (e.g., stability over time and context, or cost-effectiveness). As measures become more complex, the strategy of aggregating across measures is becoming increasingly essential.

What is the definition of chronic pain?

Chronic pain is defined as pain that persists at the site or areas surrounding the site of an acute painful event (surgery/injury/trauma)6 months following surgery/injury. Chronic pain intensity will be operationally defined as >3 on a 11-point scale of the worst pain rating over the prior 24 hours, assessed with the Brief Pain Inventory (BPI), at the site of surgery or areas surrounding site of the acute painful event (surgery/injury/trauma) 6 months after the acute painful event.

How will biomarkers be identified?

To identify biomarkers that predict the development of chronic pain 6-months after an acute painful event (surgery/injury/trauma), the essential information needed to make predictions will be collected prior to the diagnosis. Thus, the study design required to accomplish this goal will entail: a) pre-surgery or immediately after an acute painful event (injury/trauma) assessment of clinical, biospecimen, psychosocial, pain sensitivity and brain structure/function biomarkers; b) repeated assessments of pain, mood, sleep, function and pain medication use for 6-weeks immediately following the acute painful event (surgery/injury/trauma); c) assessment of clinical, biospecimen, psychosocial, pain sensitivity and brain structure/function biomarkers at 3-months after the acute painful event (surgery/injury/trauma); and d) assessment of the primary outcome --pain at 6-months –at 6-months after the acute painful event (surgery/injury/trauma).