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European Brain Research Institute (EBRI)
Via del Fosso di Fiorano 64

00143 - Rome


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Dr Silvia Marinelli
Physiopathology of Endocannabinoid System
The European Brain Research Institute in Rome

Research Area

NP is a form of chronic pain in which a sustained activation of nociceptive pathway cause a “maladaptive” response/plasticity of the pain circuitry in which the nociceptive transmission is enhanced and altered so that pain is felt in the absence of stimuli and the response to innocuous (allodynia) and noxious stimuli are enhanced (hyperalgesia). It can persist years and even decades after its first expression so that it is considered itself a disabling disease.
In addition to its nociceptive and the nocifensive component NP is also considered by the emotional–affective and cognitive aspects which are crucial for a whole knowledge of the pain mechanisms. In fact pain can induce impairment of cognitive processes that in turn modulate pain perception. In other words, chronic pain conditions cause depression and anxiety and vice versa patients with depression and/or anxiety feel pain intensely. To this regard, specific brain areas, such as the cingulate and somatosensory cortex, undergo changes following persistent activation of the nociceptive circuits and the synaptic strength increased due to a synaptic excitatory facilitation or reductionin inhibition. In particular, a structural reorganization, recruitment of additional brain areas, alteration of neurochemistry and disruption of the functional connectivity between different cortical regions are the main mechanisms of the chronic NP.
The major interest of our laboratory is the study of the basic mechanisms of NP in the cingulate and somatosensory cortex at both neuronal and glial level and the involvement of cannabinoid receptors (CBRs) and vanilloid receptors type-1 (TRPV1) in the emotional-affective, cognitive and sensory aspects of pain. Using a combination of electrophysiological, cellular, pharmacological and morphological techniques in a murine model of NP (the chronic constriction injury) we aim at identifying alterations of excitatory and inhibitory neurotransmission onto cortical pyramidal neurons, with a focus on changes of endocannabinoid signaling.

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5 Selected Publications

Manseau F., Marinelli S., Schwaller B., Mendez P., Prince DA., Huguenard JR., Bacci A. (2010) Desynchronization of neocortical networks by asynchronous release of GABA at autaptic and synaptic contacts from fast-spiking interneurons. PLoS Biol., 8 (9) : pii: ee1000492.

Marinelli S., Pacioni S., Cannich A., Marsicano G., Bacci A. (2009) Self-modulation of neocortical glutamatergic neurons by endocannabinoids. Nat. Neurosci., 12 : (12) 1488-90.

Marinelli S., Pacioni S., Bisogno T., Di Marzo V., Prince DA., Huguenard JR., Bacci A. (2008) The endocannabinoid 2-AG is responsible for the slow self-inhibition in neocortical interneurons. J. Neurosci., 28 (50) : 13532-41.

Marinelli S., Di Marzo V., Florenzano F., Viscomi MT., Fezza F., van der Stelt M., Bernardi G., Molinari M., Maccarroneand Mercuri NB. (2007) N-arachidonoyldopamine tunes synaptic transmission onto dopaminergic neurones by activating both cannabinoid and vanilloid receptors. Neurospychopharmacology., 32 (2) : 298-308.

Marinelli S., Connor M., Schnell SA., Christie MJ., Wessendorf MW., Vaughan CW. (2005) Delta-opioid receptor-mediated actions on rostral ventromedial medulla neurons. Neuroscience., 132 (2) : 239-44.

Awards, Fellowships and Honours

2004            Travel Grant, FENS Meeting-Lisbon 2004
2002            33rd Course of the International School of Biophysics ”A.Borsellino”
1999            Electrical Signalling in the CNS, Course at International School for Advanced Studies
1999            CNR, National Council of the Research, Research Training Awards ( until 2000)
2010            Italian Ministry of Health, Young Investigator Awards
2012            International Astrocytes School, Bertinoro, Italy

Technical Expertise
  • Endocannabinoid system and synaptic transmission
  • Vanilloid receptors type-1 (TRPV1) in the brain
  • Chronic pain and epilepsy
  • Cortical microcircuits
  • Electrophysiology in ex vivo (acute brain slices)
  • Anatomy/confocal microscopy and morphology reconstruction
  • In vivo labelling: injection of retrograde fluorescent dyes in the rat spinal cord under anesthesia