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Fifty-seven level I trauma center nurses/physicians participated in a 4-day intervention to learn relaxed alertness using mindfulness-based instructions and EEG neurofeedback. Neurofeedback was provided by a Bispectral Index TM (BIS) system that continuously displays a BIS value (0-100) on the monitor screen. Reductions in the BIS value indicate that power in a high-frequency band (30-47 Hz) is decreased and power in an intermediate band (11-20 Hz) is increased. A wellbeing tool with four positive affect and seven negative affect items based on a 5-category Likert scale was used. The wellbeing score is the sum of the positive affect items (positive affect score) and the reverse-scored negative affect items (non-stress score). Of functional concern were four negative affect items rated as moderately, quite a bit, or extremely in a large percent. Of greater concern were all four positive affect items rated as very slightly or none at all, a little, or moderately in over half of the participants. Mean and nadir BIS values were markedly decreased during neurofeedback when compared to baseline values. Post-session relaxation scores were higher than pre-session relaxation scores. Post-session relaxation scores had an inverse relationship with mean and nadir BIS values. Mean and nadir BIS values were inversely associated with NFB cognitive states (i.e., widening the visual field, decreasing effort, attention to space, and relaxed alertness). For all participants, the wellbeing score was higher on day 4 than on day 1. Participants had a higher wellbeing score on day 4 than a larger group of nurses/physicians who did not participate in the BIS neurofeedback trial. Eighty percent of participants demonstrated an improvement in the positive affect or non-stress score on day 4, when compared to day 1; the wellbeing, non-stress, and positive affect scores were substantially higher on day 4 than on day 1. Additionally, for that 80% of participants, the improvements in wellbeing and non-stress were associated with reductions in day 3 BIS values. These findings indicate that trauma center nurses/physicians participating in an EEG neurofeedback trial with mindfulness instructions had improvements in wellbeing. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03152331. Registered May 15, 2017., (Copyright © 2019 Dunham, Burger, Hileman, Chance, Hutchinson, Kohli, DeNiro, Tall and Lisko.)

Intraplantar formalin injection is widely used as an experimental model of tonic pain. We investigated the role of endogenous micro-opioid receptor mechanisms in formalin-induced nocifensive behavior in mice. The flinching response induced by formalin (2%, 20 microl) was studied in mice with normal (wild type, n = 8) and absent (homozygous micro-opioid receptor knockout, n = 8) micro-opioid receptor levels. The flinch responses were counted every 5 min for 60 min post-formalin injection. Lumbar spinal cord (L4, 5) was harvested 2 h post-formalin injection to examine c-Fos expression using immunohistochemistry. The effects of naloxone (5 mg/kg, sc) administered 30 min before the intraplantar formalin injection on the flinching response of wild-type mice (n = 7) were also recorded. The second-phase formalin response (10-60 min after formalin) was higher in homozygous micro-opioid receptor knockout mice compared to the wild-type mice (P < 0.01). Naloxone administration in wild-type mice before formalin injection resulted in pain behavior similar to that observed in homozygous micro-opioid receptor knockout mice (P > 0.05). The c-Fos expression induced by formalin injection in the knockout mice was not different from that observed in wild-type mice. Our results suggest that the endogenous micro-opioid system is activated by intraplantar formalin injection and exerts a tonic inhibitory effect on the pain behavior. These results suggest an important modulatory role of endogenous micro-opioid receptor mechanisms in tonic pain states.