Effect of daily treadmill running exercise on masseter muscle nociception associated with social defeat stress in mice.

We investigated the effects of social defeat stress (SDS) and treadmill running on masseter muscle nociception, which was quantified by the orofacial formalin test and c-Fos and FosB immunoreactivities in the upper cervical spinal cord (C1/C2) region in male mice. After daily SDS or non-SDS conditioning for 10 days, SDS-conditioned mice were categorized into SDS-susceptible versus resilient mice. Several mice, including non-SDS-conditioned, SDS-susceptible, and resilient mice, were selected to assess masseter muscle nociception on Day 11. SDS conditioning for 10 days increased masseter muscle-evoked nocifensive behaviors and c-Fos and FosB expression in SDS-susceptible compared to non-SDS and resilient mice. The remaining SDS-susceptible and non-SDS mice were subjected to an additional 10 days of SDS plus treadmill running or sedentary sessions before assessing masseter muscle nociception on Day 21. Daily treadmill running sessions reduced enhanced masseter muscle nociception in SDS-susceptible mice but not in non-SDS mice. The preventive effects of daily treadmill running immediately after each SDS conditioning for 10 days on orofacial nocifensive behaviors were assessed on Day 11. Treadmill running conducted immediately after daily SDS inhibited enhanced orofacial nocifensive behaviors. These findings indicate that repeated SDS increases masseter muscle nociception, which could be prevented by daily treadmill running exercise.

ROCK inhibitors enhance bone healing by promoting osteoclastic and osteoblastic differentiation.

Osteoclast and osteoblast are essential for proper bone development and remodeling as well as recovery of bone fracture. In this study, we seek chemical compounds that enhance turnover of bone metabolism for promoting bone healing. First, we screen a chemical library which includes 378 compounds by using murine pre-osteoclastic RAW264.7 cells to identify compounds that promote osteoclastic differentiation. We find that two ROCK (Rho-associated coiled-coil kinase) inhibitors, HA-1077 (Fasudil) and Y-27632, enhance osteoclastogenesis. Subsequently, we identify that these two compounds also increase osteoblastic differentiation of MC3T3-E1 cells. Finally, our in vivo experiment shows that the local administration of ROCK inhibitors accelerate the bone healing of the rat calvarial defect.

Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

The interactions between different tastes on initiation of reflex swallow elicited by electrical stimulation in humans.

The act of eating is a source of pleasure for people and is a major factor in maintaining a good quality of life. Several types of products for dysphagia patients are available to decrease aspiration of food that often accompanies daily food intake. The final goal of these products is to improve the ease of forming a food bolus and/or the safety of the swallowing process; however, tastes of products are not a major concern with initiation of swallowing. In the present study, we investigated the effect of bitter taste stimuli (quinine) and the combination of quinine and umami (monosodium glutamate: MSG) applied to the oropharynx on reflex swallows evoked by electrical stimulation to the oropharyngeal mucosa. Each of the distilled water (DW), quinine and quinine-MSG mixture solution (volume of each solutions, 100 µl) was applied 1 s prior to electrical stimulation. No swallow was evoked when each of the solutions was applied without electrical stimulation. The application of DW and lower concentration of quinine (<100 µM) did not affect the latency of reflex swallow, but 100 µM quinine application increased the latency of the reflex swallow. In addition, application of quinine-MSG mixture solution counteracted the increase in latency induced by quinine application alone. These findings suggest that MSG enhances the initiation of swallowing along with its well-known increase in appetite stimulation. Adding MSG might be effective when creating food to promote swallowing.