Injuries of various types occur commonly in the lives of humans and other animals and lead to a pattern of persistent pain and recuperative behaviour that allows safe and effective recovery. In this Perspective, we propose a control-theoretic framework to explain the adaptive processes in the brain that drive physiological post-injury behaviour. We set out an evolutionary and ethological view on how animals respond to injury, illustrating how the behavioural state associated with persistent pain and recuperation may be just as important as phasic pain in ensuring survival. Adopting a normative approach, we suggest that the brain implements a continuous optimal inference of the current state of injury from diverse sensory and physiological signals. This drives the various effector control mechanisms of behavioural homeostasis, which span the modulation of ongoing motivation and perception to drive rest and hyper-protective behaviours. However, an inherent problem with this is that these protective behaviours may partially obscure information about whether injury has resolved. Such information restriction may seed a tendency to aberrantly or persistently infer injury, and may thus promote the transition to pathological chronic pain states.
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We thank P. Mahajan for valuable feedback and comments. The work was partially supported by the US National Science Foundation (CBET-1835000 to Z.S.C. and IOS-2047331 to R.J.C.), the US National Institutes of Health (NS121776 and DA056394 to Z.S.C.), the Wellcome Trust (214251), Versus Arthritis (21357, 21192), the Institute of Information & Communications Technology Planning & Evaluation (IITP) (2019-0-01371), and EPSRC EP/W03509X/1 to B.S., and the Frontiers Group of the Paul G. Allen Foundation to R.J.C.
The authors declare no competing interests.
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Seymour, B., Crook, R.J. & Chen, Z.S. Post-injury pain and behaviour: a control theory perspective. Nat Rev Neurosci 24, 378–392 (2023). https://doi.org/10.1038/s41583-023-00699-5