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

PLoS Comput Biol. 2026 Jan 22;22(1):e1013538. doi: 10.1371/journal.pcbi.1013538. eCollection 2026 Jan.

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.

MeSH terms

  • Animals
  • Chronic Pain / physiopathology
  • Computational Biology
  • Computer Simulation
  • Homeostasis* / physiology
  • Humans
  • Markov Chains
  • Models, Biological*
  • Pain* / physiopathology
  • Wounds and Injuries* / complications
  • Wounds and Injuries* / physiopathology