Antinociceptive effect of intermittent fasting via the orexin pathway on formalin-induced acute pain in mice.

It has been suggested that stress responses induced by fasting have analgesic effects on nociception by elevating the levels of stress-related hormones, while there is limited understanding of pain control mechanisms. Here, we investigated whether acute or intermittent fasting alleviates formalin-induced pain in mice and whether spinal orexin A (OXA) plays a role in this process. 6, 12, or 24 h acute fasting (AF) and 12 or 24 h intermittent fasting (IF) decreased the second phase of pain after intraplantar formalin administration. There was no difference in walking time in the rota-rod test and distance traveld in the open field test in all groups. Plasma corticosterone level and immobility time in the forced swim test were increased after 12 h AF, but not after 12 h IF. 12 h AF and IF increased not only the activation of OXA neurons in the lateral hypothalamus but also the expression of OXA in the lateral hypothalamus and spinal cord. Blockade of spinal orexin 1 receptor with SB334867 restored formalin-induced pain and spinal c-Fos immunoreactivity that were decreased after 12 h IF. These results suggest that 12 h IF produces antinociceptive effects on formalin-induced pain not by corticosterone elevation but by OXA-mediated pathway.

Four-week inhalation toxicity, mutagenicity and immunotoxicity studies of Keum-Yeon-Cho (NosmoQ), tobacco substitute composition, in mice.

Safety of Keum-Yeon-Cho (NosmoQ), a tobacco substitute composition, was evaluated in terms of acute- and 4 weeks repeated-inhalation toxicity, mutagenicity, and immunotoxicity using Balb/c mice. The air inside the inhalation chamber was collected and analyzed by GC-MS. In acute inhalation toxicity test, male and female mice were exposed to 40 Keum-Yeon-Cho cigarettes. The 50% lethal concentration (LC(50)) of NosmoQ was considered to be much higher than 40 cigarettes in both sexes. In 4-week repeated inhalation toxicity test, male and female mice were exposed for 6 h/day, 5 days/week for 4 weeks to 10 and 20 cigarettes per day, while control mice were exposed to filtered air. Our data indicated that no observed adverse effect level (NOAEL) of Keum-Yeon-Cho should be over 20 cigarettes per day. Results of Salmonella typhimurium reversion assay with/without histidine moiety, in vivo chromosomal aberration and in vivo micronucleus assays using mouse bone marrow cells revealed that Keum-Yeon-Cho has no mutagenicity. Evaluation of peripheral cellular immunity of mice treated with Keum-Yeon-Cho using in vitro lymphocyte proliferation assay showed no significant difference in mean stimulation index (SI) between mice exposed to Keum-Yeon-Cho and control mice. Mean CO concentrations and total particulate matter contents of 10 and 20 cigarettes were 21.1±1.23 and 40.7±1.21 ppm (mean±S.D., n=5), and 25.7±3.09 and 59.0±4.0 mg dry weight (mean±S.D., n=5), respectively. Although at negligible concentration (less than ppb level) several polycyclic aromatic hydrocarbons (PAHs) were also detected, these results indicate that NosmoQ has no toxic effect on mice.