M Dusch1, M Schley, O Obreja, E Forsch, M Schmelz, Roman Rukwied. 1. Department of Anaesthesiology and Intensive Care Medicine, University Medicine Mannheim, Ruprecht-Karls-University Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Abstract
OBJECTIVE: We compared the characteristics of neurogenic flare responses in human and pig skin to establish a translational research animal model. MATERIAL AND SUBJECTS: Eight domestic pigs and six male subjects were investigated. TREATMENT: Electrical pulses were delivered transcutaneously with increasing current intensities, pulse frequencies and pulse widths. METHODS: Inflammatory skin responses were recorded by laser Doppler imaging and analyzed by ANOVA and Fisher's (LSD) post hoc test. RESULTS: Transcutaneous stimuli of 5 mA onward induced a significant flare development in humans. In the pig, significantly lower currents of 2.5 mA already induced a flare response. Smaller flare sizes of about 3.5 cm(2) were analyzed. The flare continuously declined despite ongoing stimulation. CONCLUSIONS: Lower excitation thresholds and smaller receptive fields of nociceptors can be suggested in pigs. Impaired neuropeptide release, altered vesicle replenishment, different neuropeptide sensitivity, or insufficient peripheral decoding of action potentials may contribute to steadily decreasing flare responses. These attributes may be objectives of pre-clinical anti-hyperalgesic studies and their accurate analysis in pigs reveals a particularly sensitive translational animal model for nociceptor researches.
OBJECTIVE: We compared the characteristics of neurogenic flare responses in human and pig skin to establish a translational research animal model. MATERIAL AND SUBJECTS: Eight domestic pigs and six male subjects were investigated. TREATMENT: Electrical pulses were delivered transcutaneously with increasing current intensities, pulse frequencies and pulse widths. METHODS: Inflammatory skin responses were recorded by laser Doppler imaging and analyzed by ANOVA and Fisher's (LSD) post hoc test. RESULTS: Transcutaneous stimuli of 5 mA onward induced a significant flare development in humans. In the pig, significantly lower currents of 2.5 mA already induced a flare response. Smaller flare sizes of about 3.5 cm(2) were analyzed. The flare continuously declined despite ongoing stimulation. CONCLUSIONS: Lower excitation thresholds and smaller receptive fields of nociceptors can be suggested in pigs. Impaired neuropeptide release, altered vesicle replenishment, different neuropeptide sensitivity, or insufficient peripheral decoding of action potentials may contribute to steadily decreasing flare responses. These attributes may be objectives of pre-clinical anti-hyperalgesic studies and their accurate analysis in pigs reveals a particularly sensitive translational animal model for nociceptor researches.
Authors: Frank L Rice; David Castel; Elizabeth Ruggiero; Marilyn Dockum; George Houk; Itai Sabbag; Phillip J Albrecht; Sigal Meilin Journal: Neurobiol Pain Date: 2018-07-20