Neuroanatomical and neurochemical substrates mediating fear-induced antinociception: A systematic review of rodent preclinical studies

Abstract

Fear-induced antinociception (FIA), an instinctive defensive response producing pain suppression in stressful and/or dangerous situations, has been the subject of extensive research to elucidate the mechanisms involved in triggering and controlling pain during emotional disorders. In this systematic review, we synthesized pre-clinical studies that demonstrated the neural hodology and the neurochemical bases of FIA in laboratory animals. The literature search in PubMed, Web of Science, Science Direct, and Scopus, from inception up to July 2022, retrieved 797 articles from which 50 studies were included in this review. This review highlights key encephalic regions implicated in the modulation of FIA, such as the prefrontal cortex, the amygdaloid complex, the hippocampus, the hypothalamus, the corpora quadrigemina, the periaqueductal gray matter, and some reticular formation nuclei. FIA-related neural pathways, neurotransmitters and neuromodulators such as glutamatergic, serotonergic, norepinephrine, GABAergic, nitrergic, opioidergic and endocannabinoid connections across these encephalic regions were also addressed. Understanding these neural circuits and molecular neural mediation sheds light on the complex interplay between fear, anxiety, and pain modulation, offering potential avenues for therapeutic interventions targeting pain management in the context of heightened emotional states.