Work

Homeostasis after injury: How intertwined inference and control underpin post-injury pain and behaviour

Year: 2026

Type: article

Abstract: Injuries are an unfortunate but inevitable fact of life, leading to an evolutionary mandate for powerful homeostatic processes of recovery and recuperation. The physiological responses of the body and the immune system must be coordinated with behaviour to allow protected time for this to happen, and to prevent further damage to the affected bodily parts. Reacting appropriately requires an internal control system that represents the nature and state of the injury and specifies and withholds actions accordingly. We bring the formal uncertainties embodied in this system into the framework of a partially observable Markov decision process. We discuss nociceptive phenomena in light of this analysis, noting particularly the counter-intuitive behaviours associated with injury investigation, and the propensity for transitions from normative, tonic, to pathological, chronic pain states. Importantly, these simulation results provide a quantitative account and enable us to sketch a much needed roadmap for future theoretical and experimental studies on injury, tonic pain, and the transition to chronic pain. A uthor S ummary Several arguments suggest that the brain has a dedicated representation of the state of an injury. This provides an internal control system to modulate our behaviour, influencing the pain, anxiety, and mood changes appropriate to the need for heightened protection and recuperation during healing. Here, we propose a computational architecture for how this system might be constructed. We model the injury as a problem where its true state is only partially observable, requiring the brain to combine inference with optimal control to make decisions. We show how this framework offers an explanation of two core paradoxical observations: it explains behaviours such as rubbing or probing an injured area so as to gain information and reduce uncertainty, and it accounts for the high propensity of an injury to transition into a pathological, chronic pain state via information restriction. Overall, this provides a quantitative framework for mapping the body’s healing processes to their underlying neural substrates. This has the potential to help researchers identify novel targets for treating and possibly preventing chronic pain.

Source: PLoS Computational Biology

DOI: 10.1371/journal.pcbi.1013538

Authors: Pranav Mahajan, Peter Dayan, Ben Seymour

Institutions: University of Oxford, Max Planck Institute for Biological Cybernetics, University of Tübingen

Language: English

Topic: Pain Mechanisms and Treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,043