Neurobiology of Pet Loss Grief: A Review from a One Health Perspective

The loss of a companion animal can provoke grief whose intensity rivals human bereavement, yet its biological basis remains largely uncharted. This structured narrative review synthesizes neurobiological, endocrinological, immunological, and psychosocial evidence into a mechanistic framework offered not as established fact but as a source of testable hypotheses. We trace the substrates of the human–animal bond across six interacting systems and propose how disruption of each upon an animal’s death may drive grief. Three carry comparatively robust analogical support (oxytocinergic signaling, hypothalamic–pituitary–adrenal [HPA] axis regulation, and neuroinflammatory activation) and three are more exploratory (dopaminergic, serotonergic, and endocannabinoid pathways). Integrating extracted study-level data into transparent prioritization heuristics, we identify the HPA axis, assessed with its coupled oxytocinergic partner, as the most defensible first target for a direct biomarker study, a conclusion robust across three methodologically independent analyses. No direct pet-loss evidence yet supports any proposal, and this gap is the review’s central motivation. As applied context, we address euthanasia-related guilt, disenfranchised grief under East Asian norms (a tentative “double disenfranchisement” hypothesis that we put forward for testing), assessment instruments, evidence-graded therapies, priorities for developing Korean-language tools, and One Health research priorities.