Spinal trigeminal neurons demonstrate an increase in responses to dural electrical stimulation in the orofacial formalin test

Primary headaches are often associated with pain in the maxillofacial region commonly classified under the term “orofacial pain” (OFP). In turn, long-lasting OFP can trigger and perpetuate headache as an independent entity, which is able to persist after the resolution of the main disorder. A close association between OFP and headache complicates their cause and effect definition and leads to misdiagnosis. The precise mechanisms underlying this phenomenon are poorly understood, partly because of the deficiency of research-related findings. We combined the animal models of OFP and headache—the orofacial formalin test and the model of trigeminovascular nociception—to investigate the neurophysiological mechanisms underlying their comorbidity. In anesthetized rats, the ongoing activity of single convergent neurons in the spinal trigeminal nucleus was recorded in parallel to their responses to the electrical stimulation of the dura mater before and after the injection of formalin into their cutaneous receptive fields. Subcutaneous formalin resulted not only in the biphasic increase in the ongoing activity, but also in an enhancement of neuronal responses to dural electrical stimulation, which had similar time profile. These results demonstrated that under tonic pain in the orofacial region a nociceptive signaling from the dura mater to convergent trigeminal neurons is significantly enhanced apparently because of the development of central sensitization; this may contribute to the comorbidity of OFP and headache

Network Topologies and Dynamics Leading to Endotoxin Tolerance and Priming in Innate Immune Cells

The innate immune system, acting as the first line of host defense, senses and adapts to foreign challenges through complex intracellular and intercellular signaling networks. Endotoxin tolerance and priming elicited by macrophages are classic examples of the complex adaptation of innate immune cells. Upon repetitive exposures to different doses of bacterial endotoxin (lipopolysaccharide) or other stimulants, macrophages show either suppressed or augmented inflammatory responses compared to a single exposure to the stimulant. Endotoxin tolerance and priming are critically involved in both immune homeostasis and the pathogenesis of diverse inflammatory diseases. However, the underlying molecular mechanisms are not well understood. By means of a computational search through the parameter space of a coarse-grained three-node network with a two-stage Metropolis sampling approach, we enumerated all the network topologies that can generate priming or tolerance. We discovered three major mechanisms for priming (pathway synergy, suppressor deactivation, activator induction) and one for tolerance (inhibitor persistence). These results not only explain existing experimental observations, but also reveal intriguing test scenarios for future experimental studies to clarify mechanisms of endotoxin priming and tolerance.Comment: 15 pages, 8 figures, submitte

Nocturnal masseter EMG activity of healthy subjects in a natural environment.

Facial pain of patients with craniomandibular disorders might be caused by muscle overload. However, the activity of masticatory muscles of healthy individuals is still unknown. The aim of this study was therefore a first attempt to clarify this question by recording the masseter muscle activity of healthy subjects during sleep by means of portable recorders. The study was performed on 21 healthy subjects selected after telephone and questionnaire screenings and clinical examination from among randomly selected inhabitants of Zürich. The masseter EMG was recorded during seven nights in each subject's natural environment with the electrodes in reproducible position. The signal was analyzed for number, amplitude, and duration of contraction periods defined as signal portions above a threshold which could contain sub-threshold signal portions shorter than the standby time of 5 sec. The signal amplitude was expressed in percent of the amplitude recorded during maximum voluntary clenches (%MVC). An average of 71.9 +/- 28.7 contraction episodes per night (men, 74.7 +/- 30.1; women, 65.0 +/- 23.8; p = 0.043), i.e., of 10.5 +/- 3.8 per hour (men, 11.0 +/- 4.0; women, 9.3 +/- 3.0; p = 0.005), was found. The average mean amplitude was 26.2 +/- 6.4% MVC (men, 27.0 +/- 6.8; women, 24.4 +/- 4.5; p = 0.009). The duration of the episodes had a mode of 0.5 sec, and the group mean of the integral of the amplitude over time was 123.7 +/- 157.9% MVC (men, 138.9 +/- 184.0; women, 85.9 +/- 28.2; p = 0.005). Healthy subjects showed intermittent periods of masseter activity during sleep which, on average, were of rather low intensity and short duration

The role of the feedforward paradigm in cognitive psychology

Feedforward control is a process adjusting behaviour in a continuative way. Feedforward takes place when an equilibrium state is disrupted and the system has to automatically retrieve the homeostatic stable state. It also occurs when a perturbation is previewed and must be eliminated in order to achieve a desired goal. According to the most general definition, a feedforward process operates by fixing the future representation of the desired state, the achieving of which stops the process. Then, feedforward works by means of the refinement determined by successive comparisons between the actual and target products. In its applications, a feedforward process is thought to be modulated by the subject's purpose and the environmental state. Over the years, the feedforward process has assumed different connotations in several contests of cognitive psychology. An overview of the research fields in psychology that significantly progressed with the introduction of a feedforward paradigm is provided by: (a) reviewing models in which the feedforward concept plays a fundamental role in the system control; (b) examining critical experiments related to the interaction of feedforward and feedback processes; (c) evidencing practical applications for some of the presented feedforward-based architectures. © Marta Olivetti Belardinelli and Springer-Verlag 2006