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Critical for organismal survival, pain evokes strong physiological and behavioral responses in various sentient species. Clinical and preclinical (animal) studies markedly increase our understanding of biological consequences of developmental (early-life) adversity, as well as acute and chronic pain. However, the long-term effects of early-life pain exposure on human and animal emotional responses remain poorly understood. Here, we discuss experimental models of nociception in rodents and zebrafish, and summarize mounting evidence of the role of early-life pain in shaping emotional traits later in life. We also call for further development of animal models to probe the impact of early-life pain exposure on behavioral traits, brain disorders and novel therapeutic treatments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The Van Gogh-like 2 (vangl2) gene is typically associated with planar cell polarity pathways, which is essential for correct orientation of epithelial cells during development. The encoded protein of this gene is a transmembrane protein and is highly conserved through evolution. Van Gogh-like 2 was selected for further study on the basis of consistent regulation after a nociceptive stimulus in adult common carp and rainbow trout in a microarray study. An in situ hybridisation was conducted in the brain of mature common carp (Cyprinus carpio), 1.5 and 3 h after a nociceptive stimulus comprising of an acetic acid injection to the lips of the fish and compared with a saline-injected control. The vangl2 gene was expressed in all brain regions, and particularly intensely in neurons of the telencephalon and in ependymal cells. In the cerebellum, a greater number (P=0.018) of Purkinje cells expressed vangl2 after nociception (n=7) compared with controls (n=5). This regulation opens the possibility that vangl2 is involved in nociceptive processing in the adult fish brain and may be a novel target for central nociception in vertebrates.

Recent studies have demonstrated that teleost fish possess nociceptors that detect potentially painful stimuli and that the physiological properties of these fibres are markedly similar to those found in mammals. This finding led to suggestions of possible pain perception in fish, contrary to the view that the sensory response in these animals is limited to the spinal cord and hindbrain and as such is reflexive. Therefore, the aim of this study was to determine if the brain is active at the molecular level by using a microarray analysis of gene expression in the forebrain, midbrain and hindbrain of two fish species. A comparison between the two species at different time points showed that many genes were differentially regulated in response to a noxious stimulus compared with controls. A number of genes that are involved in mammalian nociception, such as brain-derived neurotrophic factor (BDNF) and the cannabinoid CB1 receptor were regulated in the fish brain after a nociceptive event. Novel candidates that showed significant regulation in both species were also identified. In particular, the Van Gogh-like 2 gene, was regulated in both carp and trout and should be pursued to establish its precise role in nociception.

Corneal receptors have not previously been identified in lower vertebrates. The present study describes the properties of trigeminal ganglion corneal receptors in a teleost fish, the rainbow trout (Oncoryhnchus mykiss). Out of 27 receptors, 7 were polymodal nociceptors, 6 were mechanothermal nociceptors, 2 were mechanochemical receptors and the largest group, 12, were only responsive to mechanical stimulation. No cold responsive receptors were found on the trout cornea. Mechanical and thermal thresholds were lower and receptive field diameters smaller than those of cutaneous trigeminal receptors in the trout, demonstrating greater sensitivity in the cornea. The lack of cold sensitive neurons may provide evidence for the evolution of cold nociceptors in vertebrates that is related to the transition from poikilothermy to homeothermy.

The trigeminal nerve in the rainbow trout, Oncorhynchus mykiss, was examined for the presence of A-delta and C fibres. Sections of the three branches of the trigeminal nerve were found to comprise a range of fibre types including A-delta and C fibres. The size range of the cell bodies of the trigeminal ganglion reflected the fibre range since they correlated with the size range of axons in the nerve branches. Electrophysiological recordings of evoked activity from the ganglion confirmed the presence of these fibre types and the proportion of these mirrored the proportion of fibre types in the anatomical analyses. A-beta fibres were most common followed by A-delta fibres, then A-alpha fibres with C fibres being the fewest fibre type found. In higher vertebrates, A-delta and C fibres in the trigeminal nerve convey both somatosensory and nociceptive information to the brain. The evolutionary significance of these results is discussed as well as the potential for nociceptive capability in a lower vertebrate.