From Nociception in Aneural Animals to Human Suffering: Toward a Comparative Biology of Pain

Authors

Edgar T Walters

Publication Date

10-1-2025

Journal

The Journal of Experimental Biology

DOI

10.1242/jeb.251210

PMID

41081340

PMCID

PMC12834466

PubMedCentral® Posted Date

1-27-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Pain is a core feature of human life, but systematic comparisons of this biological trait across taxa have been rare. A broadly accepted definition based on human experience emphasizes dual features of pain: a sensory (discriminative) component for sensing and monitoring tissue injury, and an affective (emotional) component to motivate avoidance of tissue distress. Conscious pain is coupled to unconscious nociception (detection of incipient or existing injury). This Review considers nociception and pain across phyla within a comparative framework, addressing basic questions about evolutionary origins, mechanisms and functions of pain. The occurrence of adaptive cellular responses to injury in virtually all organisms and the linking of related processes to nociceptive behavior from the simplest to most complex animals suggest that ancient injury-related mechanisms both in neurons and in non-neuronal cells contribute to pain. Nociceptive sensory neurons are the most investigated pain-related cell type. Common nociceptor functions include warning about imminent injury, monitoring tissue status and driving protective responses. Diverse nociceptors show conservation of receptor molecules detecting noxious stimuli, and of cell signaling pathways that produce nociceptive sensitization. Nociceptors excite central neural circuits (often exhibiting strong inhibitory and sensitizing modulation) that control protective behavior, and which are being mapped systematically in selected species. A deeper understanding of affective pain should come from defining circuit processes and behavioral functions linked to the aversiveness of nociceptive central states. Comparative studies promise continuing insights into the evolution of pain, including the possibility that nociceptive systems developed an unusual readiness to drive pain-related suffering during recent hominin evolution.

Keywords

Nociception, Animals, Humans, Pain, Nociceptors, Biological Evolution, Aversive state, Evolutionary, Ion channels, Neural circuit, Nociceptive sensitization, Nociceptor

Published Open-Access

yes

Recommended Citation

Edgar T Walters, "From Nociception in Aneural Animals to Human Suffering: Toward a Comparative Biology of Pain" (2025). Faculty, Staff and Student Publications. 6622.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6622