Chronic pain is a widespread disorder affecting millions of people and is insufficiently addressed by current classes of analgesics due to significant long-term or high dosage side effects. A promising approach that was recently proposed involves the systemic inhibition of the voltage-gated sodium channel Nav1.7, capable of cancelling pain perception completely. Notwithstanding numerous attempts, currently no drugs have been approved for the inhibition of Nav1.7. The task is complicated by the difficulty of creating a selective drug for Nav1.7, and avoiding binding to the many human paralogs performing fundamental physiological functions. In our work, we obtained a promising set of ligands with up to 5-40-fold selectivity and reaching 5.2 nanomolar binding affinity by employing a proper treatment of the problem and an innovative differential in silico screening procedure to discriminate for affinity and selectivity against the Nav paralogs. The absorption, distribution, metabolism, and excretion (ADME) properties of our top-scoring ligands were also evaluated, with good to excellent results. Additionally, our study revealed that the top-scoring ligand is a stereoisomer of an already-approved drug. These facts could reduce the time required to bring a new effective and selective Nav1.7 inhibitor to the market.

The microwave emitting Radio Electric Asymmetric Conveyor (REAC) is a technology able to interact with biological tissues at low emission intensity (2 mW at the emitter and 2.4 or 5.8 GHz) by inducing radiofrequency generated microcurrents. It shows remarkable biological effects at many scales from gene modulations up to functional global remodeling even in human subjects. Previous REAC experiments by functional Magnetic Resonance Imaging (fMRI) on healthy human subjects have shown deep modulations of cortical BOLD signals. In this paper we studied the effects of REAC application on spontaneous and evoked neuronal activities simultaneously recorded by microelectrode matrices from the somatosensory thalamo-cortical axis in control and chronic pain experimental animal models. We analyzed the spontaneous spiking activity and the Local Field Potentials (LFPs) before and after REAC applied with a different protocol. The single neuron spiking activities, the neuronal responses to peripheral light mechanical stimuli, the population discharge synchronies as well as the correlations and the network dynamic connectivity characteristics have been analyzed. Modulations of the neuronal frequency associated with changes of functional correlations and significant LFP temporal realignments have been diffusely observed. Analyses by topological methods have shown changes in functional connectivity with significant modifications of the network features.

In the last 30 years, a converging series of laboratory experiments, clinical trials, and neurocognitive studies have identified several key mechanisms of placebo effects. These studies suggest not only that placebo responses may be ubiquitous across research and clinical settings, but also that they can significantly modulate symptoms across a wide spectrum of highly prevalent conditions such as acute pain, chronic pain, anxiety, depression, Parkinson's disease, and nausea, just to name a few. In order to inform the medical community about the most recent advances in the field of placebo studies, a thematic workshop entitled "The Science of Placebo" was held at the Beth Israel Deaconesses Medical Center (BIDMC), Harvard Medical School, in Boston (MA), on the 19-20 of June 2013. The workshop, sponsored by The Robert Wood Johnson Foundation, was organised by the Program in Placebo Studies and the Therapeutic Encounter, a Harvard-wide network of researchers dedicated to the study of the placebo phenomenon hosted by the BIDMC. The event was structured as a series of four public lectures, each delivered by a leading investigator in the field of placebo studies. The four keynote speakers were Fabrizio Benedetti, professor of neurophysiology and human physiology at the University of Turin Medical School and at the National Institute of Neuroscience in Italy; Tor Wager, director of the Cognitive and Affective Control Laboratory and associate professor of psychology and neuroscience at the University of Colorado; Predrag Petrovic, psychiatrist and researcher in the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm; and Ted Kaptchuk, director of the Program in Placebo Studies and associate professor of medicine at Harvard Medical School.

Changes in the levels of either the cannabinoid CB 1 receptors or of their endogenous ligands, anandamide and 2-arachidonoylglycerol, appear to be casual or consequential in many neurological disorders. Several examples of how such diseases may be treated by substances capable of selectively manipulating endocannabinoid levels and action are presented, using animal models of neuropathological conditions, such as motor disorders, multiple sclerosis, neuronal damage, chronic and inflammatory pain, anorexia, cachexia and motivational disturbances. These examples indicate that new therapeutic agents, lacking the undesirable psychotropic side effects of Cannabis, may be developed from current studies on the endocannabinoid system.