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The RETRACE-3D project (centRal italy EarThquakes integRAted Crustal model) focused on the revision of all the available geological and geophysical data in the area interested by the 2016-2018 seismic sequence of central Italy, with the final aim to reconstruct a reliable and consistent 3D geological model of that area. It is based on a collaboration, which was framed into a formal agreement, between Dipartimento della Protezione Civile (the Italian Civil Protection Department), Istituto di Geologia Ambientale e Geoingegneria, and Istituto per il Rilevamento Elettromagnetico of the Consiglio Nazionale delle Ricerche, Istituto Nazionale di Geofisica e Vulcanologia, and Istituto Superiore per la Protezione e la Ricerca Ambientale. The agreement purpose was to develop a project aimed at the geological and seismotectonic characterisation of the crustal volume hosting that seismic sequence. We present and discuss the approach, methodology and results of the project. The 3D geological model of the study area is developed in detail down to a depth of about 12 km, and extended to the Moho based on available regional-scale information. The model is available on the RETRACE-3D project website (www.retrace3d.it).

Neuropathic pain (NP) remains an untreatable disease due to the complex pathophysiology that involves the whole pain neuraxis including the forebrain. Sensory dysfunctions such as allodynia and hyperalgesia are only part of the symptoms associated with neuropathic pain that extend to memory and affectivity deficits. The development of multi-target molecules might be a promising therapeutic strategy against the symptoms associated with NP. 2-pentadecyl-2-oxazoline (PEA-OXA) is a plant-derived agent, which has shown effectiveness against chronic pain and associated neuropsychiatric disorders. The molecular mechanisms by which PEA-OXA exerts its effects are, however, only partially known. In the current study, we show that PEA-OXA, besides being an alpha2 adrenergic receptor antagonist, also acts as a modulator at histamine H3 receptors, and report data on its effects on sensory, affective and cognitive symptoms associated with the spared nerve injury (SNI) model of neuropathic pain in mice. Treatment for 14 days with PEA-OXA after the onset of the symptoms associated with neuropathic pain resulted in the following effects: (i) allodynia was decreased; (ii) affective/cognitive impairment associated with SNI (depression, spatial, and working memories) was counteracted; (iii) long-term potentiation in vivo in the lateral entorhinal cortex-dentate gyrus (perforant pathway, LPP) was ameliorated, (iv) hippocampal glutamate, GABA, histamine, norepinephrine and dopamine level alterations after peripheral nerve injury were reversed, (v) expression level of the TH positive neurons in the Locus Coeruleus were normalized. Thus, a 16-day treatment with PEA-OXA alleviates the sensory, emotional, cognitive, electrophysiological and neurochemical alterations associated with SNI-induced neuropathic pain.

Chronic pain is associated with cognitive deficits. Palmitoylethanolamide (PEA) has been shown to ameliorate pain and pain-related cognitive impairments by restoring glutamatergic synapses functioning in the spared nerve injury (SNI) of the sciatic nerve in mice. SNI reduced mechanical and thermal threshold, spatial memory and LTP at the lateral entorhinal cortex (LEC)-dentate gyrus (DG) pathway. It decreased also postsynaptic density, volume and dendrite arborization of DG and increased the expression of metabotropic glutamate receptor 1 and 7 (mGluR1 and mGluR7), of the GluR1, GluR1s845 and GluR1s831 subunits of AMPA receptor and the levels of glutamate in the DG. The level of the endocannabinoid 2-arachidonoylglycerol (2-AG) was instead increased in the LEC. Chronic treatment with PEA, starting from when neuropathic pain was fully developed, was able to reverse mechanical allodynia and thermal hyperalgesia, memory deficit and LTP in SNI wild type, but not in PPAR? null, mice. PEA also restored the level of glutamate and the expression of phosphorylated GluR1 subunits, postsynaptic density and neurogenesis. Altogether, these results suggest that neuropathic pain negatively affects cognitive behavior and related LTP, glutamatergic synapse and synaptogenesis in the DG. In these conditions PEA treatment alleviates pain and cognitive impairment by restoring LTP and synaptic maladaptative changes in the LEC-DG pathway. These outcomes open new perspectives for the use of the N-acylethanolamines, such as PEA, for the treatment of neuropathic pain and its central behavioural sequelae.

We are writing this comment because many aspects of the analysis presented by Nappi et al. (2018) are debatable. In particular, a major issue is relevant to the conclusion suggested by Nappi et al. (2018) about a seismogenic normal fault with northward dip; this finding is not grounded because the Authors do not really present a causative source model and, above all, their statement is clearly not consistent with the DInSAR, GPS and seismological measurements presented in the manuscript previously published by De Novellis et al. (2018). Moreover, we also report an evident error in the geologic map proposed by Nappi et al. (2018), see Figure 3 of their manuscript.

We investigate the ground deformation pattern and the source geometry responsible of the 2016 Central Italy seismic sequence (CISS) by joint exploiting the Multisensors and Multiorbits satellite measurements (i.e. Sentinel-1 and ALOS 2) and the integration with the available geological/structural and seismological data. To this purpose we integrate these measurements in a physically-based optimization model scenario. We consider the new seismic sequence that struck Umbria-Marche Apennines (Central Italy) since the month of August 2016. This seismic sequence started with the Amatrice earthquake (MW 6.0) occurred on August 24th. This event nucleated along a SW dipping extensional lineament, called the Mt. Gorzano fault (e.g. Boncio et al., 2004), and caused 299 casualties and severe damages to buildings and historical monuments, devastating Amatrice itself, Accumoli and other surrounding small towns. During the following months, very numerous aftershocks have nucleated and the CISS has migrated northward (e.g. Tinti et al., 2016). On October 26th two intense events occurred with ML 5.4 and ML 5.9, respectively. Moreover, on October 30th the strongest event of the sequence occurred with MW 6.5 close to the small town of Norcia and nucleated along the Mt. Vettore extensional fault (e.g. Galadini & Galli, 2003). The involved area is still active and a lot of earthquake nucleate every day: up to now, the INGV seismic network has recorded more than 30000 events. Despite to the tectonic complexity of the 2016 CISS, we achieved a good determination/description of the ground deformation pattern thanks to the big amount of SAR data acquired by Sentinel-1 (ESA) and ALOS 2 (JAXA) satellites, characterized by small temporal baselines and from different orbits (ascending and descending orbits). In this way, we can analyse in greater detail the ground deformation pattern of the individual seismic events, also decomposing the vertical component and the east-west one. In this context SAR data are a fundamental tool to better understand the spatio-temporal evolution of 2016 CISS. In this context, the present study, benefiting from satellite and in situ information, will investigate, through a numerical optimization multiphysics approach, the most suitable geological scenario that governed the spatial and temporal evolution of the Amatrice-Norcia seismic sequence. References Boncio, P., Lavecchia, G., Milana, G., & Rozzi, B. (2004). "Seismogenesis in Central Apennines, Italy: an integrated analysis of minor earthquake sequences and structural data in the Amatrice-Campotosto area." Annals of Geophysics, vol. 47, issue 6, December 2004. Galadini, F., & Galli, P. (2003). "Paleoseismology of silent faults in the Central Apennines (Italy): the Mt. Vettore and Laga Mts. faults." Annals of Geophysics, vol. 46, issue 5, October 2003. Tinti, E., Scognamiglio, L., Michelini, A., & Cocco, M. (2016). "Slip heterogeneity and directivity of the ML 6.0, 2016, Amatrice earthquake estimated with rapid finite-fault inversion." Geophysical Research Letters, vol. 43, issue 20.

We investigate a large geodetic data set of interferometric synthetic aperture radar (InSAR) and GPS measurements to determine the source parameters for the three main shocks of the 2016 Central Italy earthquake sequence on 24 August and 26 and 30 October (M-w 6.1, 5.9, and 6.5, respectively). Our preferred model is consistent with the activation of four main coseismic asperities belonging to the SW dipping normal fault system associated with the Mount Gorzano-Mount VettoreMount Bove alignment. Additional slip, equivalent to a Mw similar to 6.1-6.2 earthquake, on a secondary (1) NE dipping antithetic fault and/or (2) on a WNW dipping low-angle fault in the hanging wall of the main system is required to better reproduce the complex deformation pattern associated with the greatest seismic event (the Mw 6.5 earthquake). The recognition of ancillary faults involved in the sequence suggests a complex interaction in the activated crustal volume between the main normal faults and the secondary structures and a partitioning of strain release.

order to integrate and homogenize the big amount of data derived by several acquisition platform (i.e., remote sensing, geological geophysical and in situ measurements) we propose an innovative approach so called: Chain Rule Optimization Procedure (C.R.O.P.). In detail the proposed methodology is an optimization tools developed in a numerical environment able to simulate the natural phenomena in a multiphysics context; this approach allows taking in account the complex physical interactions that occurred during the evolution of a natural system. In this context, the development of physically-based model is made possible because each optimization steps of the chain represents the input of the subsequent step (figure 1). Following this approach, the achieved best-fit model represents a calibrate solution that takes into account the impact of the most relevant physical parameters involved in the observed phenomena. More Specifically, to demonstrate the capability and versatility of our proposed methodological approach, we select as case of study the Ischia Island (Southern Italy), a volcanic area characterized by very high values of heat flow, a high temperature geothermal system and relevant active long term- ground deformation processes detected via C-BAND Multiorbit DInSAR data acquisition. Accordingly, we applied the multi-sensor SBAS approach to the whole archive of SAR data (about 300 images) collected over the Ischia Island from ascending and descending orbits during the 1992-2010 time interval by the ERS-1/2 and ENVISAT sensors. In order to achieve a unitary physically based model of the active long-term ground deformation phenomena, we applied the proposed methodology starting from the collection and integration of the available geological and geophysical information acquired in the last decades by the scientific community. For the Ischia volcano case study, the first step is represented by the realization of the 3D geological model of the Ischia volcanic-hydrothermal system. More specifically, we build a 3D geological-structural and petrophysical model of the whole crust beneath the Ischia volcano by integrating geological and geophysical. This geological model represents the numerical domains for the subsequent numerical optimization procedure of the available temperature measurements (i.e., shallow and deep borehole geothermal measurements). At this stage, we also evaluate the amount of the conductive and/or convective thermal regime, in order to explain the complex status of the hydrothermal system of the island of Ischia. The 3D optimized thermal field results allow to reconstruct the 3D imaging of the B/D transition for a defined time window. Finally, a 3D fluid-dynamic model, in viscous flow approximation, is performed to highlight how the viscosity contrasts between the rocks of the ductile and brittle region modulate the long-term subsidence of the Ischia Island. This fluid-dynamic model is optimized by exploiting component of the ground deformation pattern detected via satellite multi-orbit C-Band SAR (Synthetic Aperture Radar) data acquired in the time interval 1992 - 2010. Finally, we point out that the application of the C.R.O.P proposed methodology at Ischia volcanic island highlights that the driving forces that modulates the spatial and temporal evolution of 1992-2010 long-term subsidence phenomenon, detected via advanced DInSAR Interferometry, are controlled by the coupling effects of crust rheology, which are governed by existence of the thermally anomalous igneous intrusion and by the gravitational loading of the volcano edifice.

We present the main activities and the most significant results that the Institute for Electromagnetic Sensing of the Environment (IREA) of the National Research Council (CNR) has retrieved within the framework of its collaboration with the Ministry of Economic Development (MiSE) - Directorate- General for Safety of Mining and Energy Activities National Mining Office for Hydrocarbons and Georesources (DGS-UNMIG). In particular, this agreement aims at detecting and monitoring surface deformation affecting the areas of particular interest for the DGS-UNMIG through space-borne Differential SAR (Synthetic Aperture Radar) Interferometry (DInSAR) analysis and multi-parameters and multi-physics modelling. The first ones provide information on the spatial distribution of the retrieved ground displacements and their temporal evolution, the second on the geological/geophysical processes that characterize the investigated areas. In this work, we present the preliminary results retrieved via interferometric analysis performed by exploiting SAR data acquired from the first (ERS-ENVISAT) and second (Sentinel-1) generation sensors over the Emilia-Romagna Region (North Italy) and the entire Italian Peninsula, respectively. Moreover, we performed a 3D geological-structural model of the Cavone site (Emilia-Romagna) and a 3D FEM (Finite Element Method) model for simulating the co-seismic dislocation of the M6.0 and M5.8 seismic events, which occurred on 20/05/2012 and 29/05/2012 over Emilia-Romagna region, respectively.

On 24 August 2016, at 01:36 UTC¸ the intra-Apennine extensional fault system of Central Italy released a destructive earthquake (MW 6.0). It produced widespread damage and fatalities, killing about 300 people and severely destroying the town of Amatrice and surrounding villages. After few hours, the Amatrice earthquake was followed by a significant aftershock (MW 5.5), which nucleated 15 km NW-ward. The epicentral area of the seismic sequence extends in the NNW-SSE direction, for a length of about 25-30 km. It is located at the hanging-wall of the WSW-dipping Vettore-Gorzano active extensional fault system. During the days following the main shock, a significant number of Synthetic Aperture Radar (SAR) data have been acquired from different passes and angles by the L-band ALOS-2, C-band Sentinel-1 and X-band COSMO-SkyMed satellites. This allowed us to map in a very short time the co-seismic ground displacements through the Differential SAR Interferometry (DInSAR) technique, and also to evaluate their Vertical and East-West components with high details. The generated interferometric pattern is characterized by a double-eyed co-seismic shape that spans 20 km along the NNW-SSE direction and that well coincides with the epicentral areas. We modeled the seismic source that well fit the Mw 6.2 event. In particular, for this analysis, we separately applied an analytical Okada approach as well as a 3D Finite Element (FE) numerical modeling, the latter jointly exploiting DInSAR measurements and structural-geological data. The model obtained via the FE approach suggests that the Amatrice 2016 earthquake nucleated at 8 km deep along the intersection line between the Vettoretto-Redentore and the Northern Gorzano faults, and instantly geminated in two rupture patches that radiated with an approximate bilateral symmetry on the two fault planes. The two rupture patches covered differently shaped slip area, with aspect ratio that well recalls the shape of the interferometric lobes of ground subsidence at the two faults hanging wall. The different shapes of the two lobes are partially associated to the different dip-angle of the Vettoreto-Redentore and Gorzano faults (50° ad 60° respectively). In summary, we found evidences of bilateral rupture propagating along two en-echelon faults connected at the hypocenter.

We investigate the ground deformation and source geometry of the 2016 Amatrice earthquake (Central Italy) by exploiting ALOS2 and Sentinel-1 coseismic differential interferometric synthetic aperture radar (DInSAR) measurements. They reveal two NNW-SSE striking surface deformation lobes, which could be the effect of two distinct faults or the rupture propagation of a single fault. We examine both cases through a single and a double dislocation planar source. Subsequently, we extend our analysis by applying a 3-D finite elements approach jointly exploiting DInSAR measurements and an independent, structurally constrained, 3-D fault model. This model is based on a double fault system including the two northern Gorzano and Redentore-Vettoretto faults (NGF and RVF) which merge into a single WSW dipping fault surface at the hypocentral depth (8 km). The retrieved best fit coseismic surface deformation pattern well supports the exploited structural model. The maximum displacements occur at 5-7 km depth, reaching 90 cm on the RVF footwall and 80 cm on the NGF hanging wall. The von Mises stress field confirms the retrieved seismogenic scenario.

BACKGROUND AND PURPOSE Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception. EXPERIMENTAL APPROACH Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey. KEY RESULTS Cannabidiol and CBC dose-dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick-test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB(1) adenosine A(1) and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD. CONCLUSIONS AND IMPLICATIONS CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action.