Computational modeling based on hypothalamic-pituitary-adrenal (HPA) axis activity history may allow to shed light on the mechanisms of pain and the transition from acute to chronic low back pain (LBP), according to a study published in the Journal of Translational Medicine

Researchers used a predictive outcome model as a preliminary step to understand the pain transition from an acute to a chronic condition in individuals with LBP. The goal was to establish a proof-of-concept to demonstrate the feasibility of applying a computational model to predict pain trajectories. 

Investigators used a computational neuroscience-based method, stemming from the use of HPA axis activity-history, to simulate pain trajectories. Increasing evidence supports the notion that relative hypocortisolism, a marker of stress-induced HPA axis dysfunction, may increase the odds of developing chronic pain disorders. Here, cortisol level was used as a biomarker for pain trajectory. The modeling strategy required a coupled system of ordinary differential equations to represent the network of brain regions along the HPA axis and its cortisol and adrenaline production.

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The outcome measures of LBP intensity and frequency were chosen to develop the pain trajectory modeling study in LBP. To construct the pain trajectory of the patient groups, the investigators chose a sample of 100 values randomly generated by a computer of reduced adreno-corticotrophin hormone degradation rate and the stress coefficient. The time-series data of cortisol level was simulated for a period of 100 days, based on the computational HPA axis model. The 100 days were divided into 3 groups using subjective thresholds (0.556 and 0.552 in this model) of cortisol level as a high-pain day for cortisol levels ≫0.556, healed day for cortisol levels <0.556 and >>0.552, and low-pain for cortisol levels <0.552 for trajectory studies.

Study limitations include the lack of accounting for a patient’s activity limitation and the fact that the predictive modeling is mainly reliant on HPA hormonal dynamics.

“Many trajectory patterns have been proposed in the CLBP population, and we must develop a cohesive understanding of how and why these patterns are emerging in order to provide the best possible medical care for those suffering with pain,” concluded the study authors.

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Su J, Du Y, Bevers K, et al. Transitioning from acute to chronic pain: a simulation study of trajectories of low back pain. [published online September 6, 2019]. J Transl Med. doi: 10.1186/s12967-019-2030-0