No abstract

Although the antinociceptive effect of NMDA antagonists in the formalin test is well recognised, these compounds can induce adverse motor effects. The aim of this study was to identify the systemic doses of NMDA antagonists that induce analgesia without causing side effects. Male Swiss mice (30-40g) received a subcutaneous (sc) injection of 1.25% formalin (50 micro l) in the dorsal surface of the right hind-paw and, 15min before or after formalin, an ip injection of one of the following NMDA receptor antagonists: MK 801 (0.01, 0.025, and 0.05mg/kg), memantine (0.1, 0.5, and 1mg/kg), ketamine (0.125, 0.25, and 0.5mg/kg), dextromethorphan (5, 10, and 20mg/kg), and CGP 37849 (4, 6, and 8mg/kg). Pain-related behaviour (licking, lifting, favouring, shaking, and flinching of the treated paw) was recorded at 5-min intervals for 60min. The NMDA receptor antagonists significantly (p<0.01) and dose-dependently reduced, versus controls, nociceptive activity during the second phase of the formalin test (from the 20th to the 60thmin): at the highest doses, 97.6+/-0.1% with MK 801; 90.4+/-0.2% with memantine; 74.7+/-0.3% with ketamine; 92.8+/-0.4% with dextromethorphan; and 80.7+/-0.3% with CGP 37849, without affecting coordination. The rank order potency of antinociceptive activity of NMDA antagonists was: MK801>memantine>ketamine>dextromethorphan>CGP37849. The NMDA antagonists administered after formalin (during the analgesic interval) did not affect the late phase of the formalin test. In conclusion, systemic administration of NMDA receptor antagonists decreases the nociception observed during the late phase of the formalin test.

Force‐based seismic design involves the reduction of elastic spectra by introducing a behavior factor, q. This approach is widespread in engineering practice; however, recent studies have shown that structures consistently designed at different sites will not share the same level of seismic risk, which can be defined as the annual rate of the structure failing to meet a seismic performance objective, despite seismic actions having the same exceedance return period at all sites. This paper investigates whether the definition of site‐specific q factors can lead to uniform risk across sites characterized by varying levels of seismic hazard, based on the pushover curves of bare frame reinforced concrete buildings. These pushover curves are used to establish the backbones of equivalent single degree of freedom systems with varying lateral resistance. These systems are fictitiously placed at several Italian sites and their seismic failure risk is computed by integrating their fragility, assessed by means of incremental dynamic analysis, with each site's hazard curve. By assuming an arbitrary risk threshold, the same for all sites, the corresponding lateral strength leading to said threshold is determined and the corresponding behavior factor is back calculated. As expected, risk‐targeted q factors tend to increase with decreasing seismic hazard and are highly sensitive to the shape of the hazard curve beyond the design return period. Coupled with the fact that at low hazard sites lateral strength is determined by detailing for gravity‐load design and minimum code requirements, rather than seismic design actions, the results suggest that q factor‐based design is unsuitable for warranting territorially uniform seismic safety, yet it may be suitable for setting an upper‐bound to the annual failure probability.