Laboratory environmental factors and pain behavior: the relevance of unknown unknowns to reproducibility and translation

Inhibition of acid‐sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain

“…There are many factors underlying the spectrum of sensitivity to analgesics, including genetics, sex, age and health status (Muralidharan and Smith, ; Smith and Muralidharan, ). All of these factors are equally applicable to preclinical pain studies in animals (Avsaroglu et al, ; Ji et al, ), with the addition of differing laboratory conditions and animal handling practices, which can contribute different levels of stress (Mogil, ; Mogil, ). Stress, for instance from handling or simple environment changes such as being placed in a different room, can induce substantial analgesic responses and is a confounding factor in pain studies that can result in wide variation in responses (Mogil et al, ; Mogil, ).…”

“…All of these factors are equally applicable to preclinical pain studies in animals (Avsaroglu et al, ; Ji et al, ), with the addition of differing laboratory conditions and animal handling practices, which can contribute different levels of stress (Mogil, ; Mogil, ). Stress, for instance from handling or simple environment changes such as being placed in a different room, can induce substantial analgesic responses and is a confounding factor in pain studies that can result in wide variation in responses (Mogil et al, ; Mogil, ). In order to minimize such potential sources of variation, our protocol ensured that animals were handled daily during the acclimation period to minimize stress effects and that assays were carried out blinded to minimize unconscious bias during behavioural assessment.…”

Etiology and Pharmacology of Neuropathic Pain

“…This is compounded by epigenetic modifications in humans and by the limited ability of rodent models to predict clinical efficacy (Mogil, 2017;Patel et al, 2017;Sexton et al, 2017;Yekkirala et al, 2017). Despite the realization that pain processing in males differs from that in females (Mogil, 2012b;Mifflin and Kerr, 2013;Sorge et al, 2015;Dodds et al, 2016;Melchior et al, 2016;Dickie et al, 2017;Sorge and Totsch, 2017), many preclinical studies have been done on male rodents to avoid possible complications imposed by the estrous cycle.…”

Effects of adaptation to handling on the circadian rhythmicity of blood solutes in Mongolian gerbils

“…There are many factors such as temperature, humidity, light intensity, noise, handling, cage movement, dietary schedules and transportation that may affect experimental results by producing stress in laboratory animals . If the animals have not adapted to the new environment at the procedure of experiment, their physiological state may not have returned to normal, and the biomedical research results obtained may be influenced by even quite small physiological changes . Handling and blood collection are two of the commonest operations in animal experiments and may influence physiological parameters for a period of time during the experiment.…”