Pierangelo Geppetti

University of Florence, Florens, Tuscany, Italy

Are you Pierangelo Geppetti?

Claim your profile

Publications (357)1866.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Evidence is accumulating on the role of transient receptor potential (TRP) channels, namely TRPV1, TRPA1, TRPV4 and TRPM8, expressed by C- and Aδ-fibres primary sensory neurons, in cough mechanism. Selective stimuli for these channels have been proven to provoke and, more rarely, to inhibit cough. More importantly, cough threshold to TRP agonists is increased by proinflammatory conditions, known to favour cough. Off-target effects of various drugs, such as tiotropium or desflurane, seem to produce their protective or detrimental actions on airway irritation and cough via TRPV1 and TRPA1, respectively. Thus, TRPs appear to encode the process that initiates or potentiates cough, activated by exogenous irritants and endogenous proinflammatory mediators. More research on TRP channels may result in innovative cough medicines. Copyright © 2015. Published by Elsevier Ltd.
    Current Opinion in Pharmacology 02/2015; 22C:18-23. · 4.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sympathetic fibres maintain some forms of neuropathic pain, but the underlying mechanisms are poorly understood. Therefore, this study investigated the possible involvement of transient receptor potential ankyrin 1 (TRPA1) and the role of the sympathetic nervous system (involved in sympathetically maintained neuropathic pain) in a model of neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) in mice. Systemic injection of the selective TRPA1 antagonist HC-030031 reversed the mechanical and cold allodynia that was induced by sciatic nerve chronic constriction injury (CCI). Nerve injury also sensitised mice to nociception, which was induced by the intraplantar injection of a low dose of the TRPA1 agonist allyl isothiocyanate without changing TRPA1 immunoreactivity in the injected paw. Furthermore, chemical sympathectomy produced by guanethidine largely prevented CCI-induced mechanical and cold allodynia. CCI also induced a norepinephrine-triggered nociception that was inhibited by an α-adrenoceptor antagonist, norepinephrine transporter block and monoamine oxidase inhibition. Finally, the peripheral injection of HC-030031 also largely reduced CCI-induced norepinephrine nociception and mechanical or cold allodynia. Taken together, the present findings reveal a critical role of TRPA1 in mechanical and cold hypersensitivity and norepinephrine hypersensitivity following nerve injury. Finally, our results suggest that TRPA1 antagonism may be useful to treat patients who present sympathetically maintained neuropathic pain. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 12/2014; · 2.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Use of aromatase inhibitors (AIs), exemestane, letrozole and anastrozole, for breast cancer therapy is associated with severe pain symptoms, the underlying mechanism of which is unknown. The electrophilic nature of AIs suggests that they may target the transient receptor potential ankyrin 1 (TRPA1) channel, a major pathway in pain transmission and neurogenic inflammation. AIs evoke TRPA1-mediated calcium response and current in rodent nociceptors and human cells expressing the recombinant channel. In mice, AIs produce acute nociception, which is exaggerated by pre-exposure to proalgesic stimuli, and, by releasing sensory neuropeptides, neurogenic inflammation in peripheral tissues. AIs also evoke mechanical allodynia and decreased grip strength, which do not undergo desensitization on prolonged AI administration. These effects are markedly attenuated by TRPA1 pharmacological blockade or in TRPA1-deficient mice. TRPA1 is a major mediator of the proinflammatory/proalgesic actions of AIs, thus suggesting TRPA1 antagonists for the treatment of pain symptoms associated with AI use.
    Nature Communications 12/2014; 5:5736. · 10.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with cholestatic disease have increased systemic concentrations of bile acids (BAs) and profound pruritus. The G protein-coupled BA receptor 1 TGR5 (encoded by GPBAR1) is expressed by primary sensory neurons; its activation induces neuronal hyperexcitability and scratching, by unknown mechanisms. We investigated whether the transient receptor potential ankyrin 1 (TRPA1) is involved in BA-evoked, TGR5-dependent pruritus in mice.
    Gastroenterology 09/2014; · 12.82 Impact Factor
  • The Journal of Headache and Pain 06/2014; 15(suppl 1). · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and purposeTransient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) are involved in many biological processes, including nociception and hyperalgesia. Whereas the involvement of TRPV1 in psychiatric disorders as anxiety and depression has been reported, little is known regarding the role of TRPA1 in these conditions.Experimental approachWe investigated the role of TRPA1 in mice models of depression (forced swimming test, FST) and anxiety (elevated plus maze test, EPM).Key resultsIntracerebroventricular (i.c.v.) administration of the TRPA1 antagonist (HC030031, 30 nmol/2 μl) reduced immobility time in the FST test. Similar results were obtained by oral administration of HC030031 (p.o., 30-300 mg/kg). Reduction in the immobility time in the FST induced by HC030031 (100 mg/kg) was completely prevented by pretreatment with TRPA1 agonist, cinnamaldehyde (50 mg/kg, p.o.), which per se was inactive. In the EPM test, pretreatment with cinnamaldehyde (50 mg/kg, p.o.), which per se did not affect behavior response, prevented the anxiolytic-like effect (increased open arms exploration) evoked by TRPA1 blockade (HC030031, 100 mg/kg, p.o.). Treatment with either cinnamaldehyde or HC030031 did not affect spontaneous ambulation. Finally, TRPA1-deficient mice showed anxiolytic- and antidepressant-like phenotypes in the FST test and EPM test, respectively.Conclusion and implicationsPresent findings indicate that genetic deletion or pharmacological blockade of the TRPA1 produce inhibitory activity in mouse models of anxiety and depression. Results imply that TRPA1 exerts a tonic control promoting anxiety and depression and suggests TRPA1 antagonism as an innovative strategy for the treatment of anxiety and mood disorders.
    British Journal of Pharmacology 05/2014; · 5.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute gout attacks produce severe joint pain and inflammation associated with monosodium urate (MSU) crystals leading to oxidative stress production. The transient potential receptor ankyrin 1 (TRPA1) is expressed by a subpopulation of peptidergic nociceptors and via its activation by endogenous reactive oxygen species, including hydrogen peroxide (H2O2), contributes to pain and neurogenic inflammation. The aim of the present study was to investigate the role of TRPA1 in hyperalgesia and inflammation in a model of acute gout attack in rodents. Inflammatory parameters and mechanical hyperalgesia were measured in male Wistar rats, wild-type (Trpa1(+/+)) or TRPA1-deficient (Trpa1(-/-)) male mice. Animals received intra-articular (i.a., ankle) injection of MSU. The role of TRPA1 was assessed by receptor antagonism, gene deletion or expression, sensory fiber defunctionalization, and calcitonin gene-related peptide (CGRP) release. We found that nociceptor defunctionalization, TRPA1 antagonist treatment (via i.a. or oral administration), and TRPA1 gene ablation abated hyperalgesia and inflammatory responses (edema, H2O2 generation, interleukin-1β release, and neutrophil infiltration) induced by i.a. MSU injection. In addition, we showed that MSU evoked generation of H2O2 in synovial tissue which stimulating TRPA1 producing CGRP release and plasma protein extravasation. The MSU-elicited responses were also reduced by the H2O2-detoxifying enzyme catalase and the reducing agent dithiothreitol. TRPA1 activation by MSU challenge-generated H2O2 mediates the entire inflammatory response in an acute gout attack rodent model, thus strengthening the role of the TRPA1 receptor and the H2O2 production as potential targets for treatment of acute gout attacks.
    Free Radical Biology and Medicine 04/2014; · 5.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized to a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia. This subset of nociceptors produces and releases the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), which mediate neurogenic inflammatory responses. TRPA1 is activated by a number of exogenous compounds, including molecules of botanical origin, environmental irritants, and medicines. However, the most prominent feature of TRPA1 resides in its unique sensitivity for large series of reactive byproducts of oxidative and nitrative stress. Here, the role of TRPA1 in models of different types of pain, including inflammatory and neuropathic pain and migraine, is summarized. Specific attention is paid to TRPA1 as the main contributing mechanism to the transition of mechanical and cold hypersensitivity from an acute to a chronic condition and as the primary transducing pathway by which oxidative/nitrative stress produces acute nociception, allodynia, and hyperalgesia. A series of migraine triggers or medicines have been reported to modulate TRPA1 activity and the ensuing CGRP release. Thus, TRPA1 antagonists may be beneficial in the treatment of inflammatory and neuropathic pain and migraine.
    Ergebnisse der Physiologie 03/2014; · 3.90 Impact Factor
  • Pierangelo Geppetti, Riccardo Patacchini, Romina Nassini
    [Show abstract] [Hide abstract]
    ABSTRACT: The discovery that a number of transient receptor potential (TRP) channels are expressed in a subpopulation of primary sensory neurons innervating the upper and lower airways as well as in nonneuronal cells in the airways and lungs has initiated a quest for the understanding of their role in the physiology and pathophysiology of the respiratory tract. Various members of the TRP vanilloid subfamily (TRPV1, TRPV4) and the TRP ankyrin 1 (TRPA1), because of their localization in peptidergic sensory neurons, promote airway neurogenic inflammation. In particular, TRPA1, which is gated by oxidative and nitrative stress byproducts, has been found to mediate inflammatory responses produced by an unprecedented series of toxic and irritant agents produced by air pollution, contained in cigarette smoke, and produced by accidental events at the workplace. The observation that reactive molecules endogenously produced in the airways/lungs of asthma, work-related asthma, and chronic obstructive pulmonary disease target TRPA1 underscores the primary role of the TRPA1 channel in these conditions. Identification of TRP channels, and especially TRPA1, as major targets of oxidative/nitrative stress and a variety of irritant environmental agents supports the hypothesis that neurogenic inflammation plays an important role in work-related inflammatory diseases and that antagonists for such channels may be novel therapeutic options for the treatment of these diseases.
    Current Opinion in Allergy and Clinical Immunology 01/2014; · 3.40 Impact Factor
  • Advances in Free Radical Biology & Medicine 01/2014; 72:200–209.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The tachykinins, exemplified by substance P, are one of the most intensively studied neuropeptide families. They comprise a series of structurally related peptides that derive from alternate processing of three Tac genes and are expressed throughout the nervous and immune systems. Tachykinins interact with three neurokinin G protein-coupled receptors. The signaling, trafficking, and regulation of neurokinin receptors have also been topics of intense study. Tachykinins participate in important physiological processes in the nervous, immune, gastrointestinal, respiratory, urogenital, and dermal systems, including inflammation, nociception, smooth muscle contractility, epithelial secretion, and proliferation. They contribute to multiple diseases processes, including acute and chronic inflammation and pain, fibrosis, affective and addictive disorders, functional disorders of the intestine and urinary bladder, infection, and cancer. Neurokinin receptor antagonists are selective, potent, and show efficacy in models of disease. In clinical trials there is a singular success: neurokinin 1 receptor antagonists to treat nausea and vomiting. New information about the involvement of tachykinins in infection, fibrosis, and pruritus justifies further trials. A deeper understanding of disease mechanisms is required for the development of more predictive experimental models, and for the design and interpretation of clinical trials. Knowledge of neurokinin receptor structure, and the development of targeting strategies to disrupt disease-relevant subcellular signaling of neurokinin receptors, may refine the next generation of neurokinin receptor antagonists.
    Physiological Reviews 01/2014; 94(1):265-301. · 29.04 Impact Factor
  • Source
    S Benemei, C Fusi, Gabriela Trevisan, Pierangelo Geppetti
    [Show abstract] [Hide abstract]
    ABSTRACT: Migraine remains an elusive and poorly understood disease. The uncertainty is reflected by the current unsatisfactory acute and prophylactic migraine treatment. Genetic and pharmacological information points to certain transient receptor potential (TRP) in pain mechanisms. In particular, vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) seem to play a major role in different models of pain diseases. Recent findings have underscored the possibility that TRP channels expressed in the nerve terminals of peptidergic nociceptors contribute to the migraine mechanism. Among this channel subset, TRPA1, a sensor of oxidative, nitrative and electrophilic stress, is activated by an unprecedented series of irritant and pain provoking exogenous and endogenous agents, which by this neuronal pathway release the pro-migraine peptide, calcitonin gene-related peptide (CGRP). Some of the recently identified TRPA1 activators have long been known as migraine triggers. Furthermore, specific analgesic and antimigraine medicines have been shown to inhibit or desensitise the TRPA1 channel. Thus, TRPA1 is emerging as a major contributing pathway in migraine and as a novel target for the development of drugs for pain and migraine treatment.
    British Journal of Pharmacology 11/2013; · 5.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Gout is a common cause of inflammatory arthritis and is provoked by the accumulation of monosodium urate (MSU) crystals. However, the underlying mechanisms of the pain associated with acute attacks of gout are poorly understood. The aim of this study was to evaluate the role of transient receptor potential ankyrin 1 (TRPA-1) and TRPA-1 stimulants, such as H2O2, in a rodent model of MSU-induced inflammation. MethodsMSU or H2O2 was injected into the hind paws of rodents or applied in cultured sensory neurons, and the intracellular calcium response was measured in vitro. Inflammatory or nociceptive responses in vivo were evaluated using pharmacologic, genetic, or biochemical tools and methods. ResultsTRPA-1 antagonism, TRPA-1 gene deletion, or pretreatment of peptidergic TRP-expressing primary sensory neurons with capsaicin markedly decreased MSU-induced nociception and edema. In addition to these neurogenic effects, MSU increased H2O2 levels in the injected tissue, an effect that was abolished by the H2O2-detoxifying enzyme catalase. H2O2, but not MSU, directly stimulated sensory neurons through the activation of TRPA-1. The nociceptive responses evoked by MSU or H2O2 injection were attenuated by the reducing agent dithiothreitol. In addition, MSU injection increased the expression of TRPA-1 and TRP vanilloid channel 1 (TRPV-1) and also enhanced cellular infiltration and interleukin-1β levels, and these effects were blocked by TRPA-1 antagonism. Conclusion Our results suggest that MSU injection increases tissue H2O2, thereby stimulating TRPA-1 on sensory nerve endings to produce inflammation and nociception. TRPV-1, by a previously unknown mechanism, also contributes to these responses.
    Arthritis & Rheumatology 11/2013; 65(11). · 7.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To verify preliminary studies on patients with melanoma exposed to β-blockers that suggested a reduced risk of disease recurrence and death. Data were obtained from all consecutive patients diagnosed as having melanoma between January 1, 1993, and December 31, 2009, at the Department of Dermatology of the University of Florence, Azienda Sanitaria di Firenze. Participants were excluded if at baseline they reported a previous diagnosis of cutaneous malignant melanoma or another malignant disease. We also excluded participants with evidence of visceral, lymph nodal, and in-transit metastasis at the time of the diagnosis. Of 741 consecutive patients with melanoma, 79 (11%) were prescribed β-blockers (for hypertension in most cases) for 1 or more years (treated) and 662 (89%) were not (untreated). The multivariate Cox model indicated that the treated group had improved overall survival after a median follow-up of 4 years (P=.005). For each year of β-blocker use, the risk of death was reduced by 38%. The presence of hypertension, the use of antihypertensive agents for 1 or more years, or the use of other commonly used medicines were not associated with a better outcome for patients with melanoma. The results confirm and strengthen previous findings that β-blocker use is associated with a reduced risk of melanoma recurrence and death. The results also indicate the strong need for a randomized clinical trial to conclusively assess whether β-blockers afford protection against melanoma recurrence and death.
    Mayo Clinic Proceedings 11/2013; 88(11):1196-203. · 5.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ever since their identification, interest in the role of transient receptor potential (TRP) channels in health and disease has steadily increased. Robust evidence has underlined the role of TRP channels expressed in a subset of primary sensory neurons of the trigeminal ganglion to promote, by neuronal excitation, nociceptive responses, allodynia and hyperalgesia. In particular, the TRP vanilloid 1 (TRPV1) and the TRP ankyrin 1 (TRPA1) are expressed in nociceptive neurons, which also express the sensory neuropeptides, tachykinins, and calcitonin gene-related peptide (CGRP), which mediate neurogenic inflammatory responses. Of interest, CGRP released from the trigeminovascular network of neurons is currently recognized as a main contributing mechanism of migraine attack. The ability of TRPA1 to sense and to be activated by an unprecedented series of exogenous and endogenous reactive molecules has now been extensively documented. Several of the TRPA1 activators are also known as triggers of migraine attack. Thus, TRP channels, and particularly TRPA1, may be proposed as novel pathways in migraine pathophysiology and as possible new targets for its treatment.
    The Journal of Headache and Pain 08/2013; 14(1):71. · 3.28 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: While feverfew has been used for centuries to treat pain and headaches and is recommended for migraine treatment, the mechanism for its protective action remains unknown. Migraine is triggered by calcitonin gene-related peptide (CGRP) release from trigeminal neurons. Peptidergic sensory neurons, express a series of transient receptor potential (TRP) channels, including the ankyrin 1 (TRPA1) channel. Recent findings have identified agents either inhaled from the environment or produced endogenously, which are known to trigger migraine or cluster headache attacks, as TRPA1 simulants. A major constituent of feverfew, parthenolide, may interact with TRPA1 nucleophilic sites, suggesting that feverfew antimigraine effect derives from its ability to target TRPA1. We found that parthenolide stimulates recombinant (transfected cells) or natively expressed (rat/mouse trigeminal neurons) TRPA1, where it, however, behaves as a partial agonist. Furthermore, in rodents, after initial stimulation, parthenolide desensitizes the TRPA1 channel, and renders peptidergic, TRPA1-expressing nerve terminals unresponsive to any stimulus. This effect of parthenolide abrogates nociceptive responses evoked by stimulation of peripheral trigeminal endings. TRPA1 targeting and neuronal desensitization by parthenolide inhibits CGRP release from trigeminal neurons and CGRP-mediated meningeal vasodilatation, evoked by either TRPA1 agonists or other unspecific stimuli. TRPA1 partial agonism, together with desensitization and nociceptor defunctionalization, ultimately resulting in inhibition of CGRP release within the trigeminovascular system, may contribute to the antimigraine effect of parthenolide.
    Pain 08/2013; · 5.64 Impact Factor
  • Silvia Benemei, Pierangelo Geppetti
    Headache The Journal of Head and Face Pain 07/2013; 53(7):1162-3. · 2.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.
    The Journal of clinical investigation 03/2013; · 15.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and painful adverse reaction of cancer treatment in patients that is little understood or treated. Cytotoxic drugs that cause CIPN exert their effects by increasing oxidative stress, which activates the ion channel TRPA1 expressed by nociceptors. In this study, we evaluated whether TRPA1 acted as a critical mediator of CIPN by bortezomib or oxaliplatin in a mouse model system. Bortezomib evoked a prolonged mechanical, cold, and selective chemical hypersensitivity (the latter against the TRPA1 agonist allyl isothiocyanate). This CIPN hypersensitivity phenotype that was stably established by bortezomib could be transiently reverted by systemic or local treatment with the TRPA1 antagonist HC-030031. A similar effect was produced by the oxidative stress scavenger α-lipoic acid. Notably, the CIPN phenotype was abolished completely in mice that were genetically deficient in TRPA1, highlighting its essential role. Administration of bortezomib or oxaliplatin, which also elicits TRPA1-dependent hypersensitivity, produced a rapid, transient increase in plasma of carboxy-methyllysine, a by-product of oxidative stress. Short-term systemic treatment with either HC-030031 or α-lipoic acid could completely prevent hypersensitivity if administered before the cytotoxic drug. Our findings highlight a key role for early activation/sensitization of TRPA1 by oxidative stress by-products in producing CIPN. Further, they suggest prevention strategies for CIPN in patients through the use of early, short-term treatments with TRPA1 antagonists.
    Cancer Research 03/2013; · 9.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this review is to present the preclinical, epidemiological and clinical data relevant to the association between β-blockers and melanoma progression. Preclinical studies have shown that β-adrenergic receptor (β-AR) signaling can inhibit multiple cellular processes involved in melanoma progression and metastasis. These observations have suggested the possibility that drugs originally intended for the treatment of cardiovascular disease, the β-AR blockers, may provide new therapeutic opportunities for the control of tumor progression. A large number of observational studies demonstrated the protective effect of β-blockers in breast cancer but, more recently, similar findings were also reported in other cancers such as prostate cancer and melanoma. With regard to melanoma, two recently published studies demonstrated a great reduction in the risk of disease progression for each year of treatment with β-blockers. The results from these studies have suggested a potential role for targeting the β-AR pathway in melanoma patients. Questions regarding the type of β-blocker or tumor characteristics, appropriate treatment paradigms and, most importantly, efficacy must be answered in randomized clinical studies before β-blockers can be considered a therapeutic option for patients with melanoma.
    Expert Review of Anti-infective Therapy 11/2012; 12(11):1461-7. · 3.06 Impact Factor

Publication Stats

12k Citations
1,866.58 Total Impact Points


  • 1983–2014
    • University of Florence
      • • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      • • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      • • Dipartimento di Medicina Sperimentale e Clinica
      Florens, Tuscany, Italy
  • 2013
    • Universidade Federal de Santa Maria
      Santa Maria da Boca do Monte, Rio Grande do Sul, Brazil
  • 2011
    • Santa Chiara Hospital
      Trient, Trentino-Alto Adige, Italy
  • 2010
    • French Institute of Health and Medical Research
      • Toulouse Purpan Pathophysiology Center CPTP
      Paris, Ile-de-France, France
  • 1997–2010
    • University of Ferrara
      • • Department of Clinical and Experimental Medicine
      • • Section of Pharmacology
      Ferrare, Emilia-Romagna, Italy
  • 1993–2010
    • University of California, San Francisco
      • • Department of Anesthesia and Perioperative Care
      • • Department of Surgery
      • • Cardiovascular Research Institute
      San Francisco, CA, United States
  • 2006–2008
    • Azienda Ospedaliero Universitaria Careggi
      • Emergency Intensive Care Unit
      Firenzuola, Tuscany, Italy
    • Foundation of the Carlo Besta Neurological Institute
      Milano, Lombardy, Italy
    • Federal University of Santa Catarina
      Nossa Senhora do Destêrro, Santa Catarina, Brazil
  • 2006–2007
    • Chiesi Farmaceutici S.p.A.
      Parma, Emilia-Romagna, Italy
  • 2005–2006
    • Charité Universitätsmedizin Berlin
      • Department of Pediatrics, Division of Pneumonology and Immunology
      Berlin, Land Berlin, Germany
  • 2002–2005
    • Humboldt-Universität zu Berlin
      • Clinical Psychology Research Unit
      Berlín, Berlin, Germany
    • Brown University
      Providence, Rhode Island, United States
  • 2004
    • Imperial College London
      • Faculty of Medicine
      Londinium, England, United Kingdom
    • University of Hull
      • Respiratory Medicine
      Kingston upon Hull, England, United Kingdom
  • 1996–2004
    • King's College London
      • • Institute of Pharmaceutical Science
      • • School of Biomedical Sciences
      London, ENG, United Kingdom
    • Cardiovascular Research Foundation
      New York, New York, United States
  • 2001
    • National Research Council
      Roma, Latium, Italy
  • 2000
    • Leiden University Medical Centre
      • Department of Pulmonology
      Leiden, South Holland, Netherlands
  • 1999
    • University of Padova
      Padua, Veneto, Italy
  • 1998–1999
    • University of Catania
      Catania, Sicily, Italy
    • Dokkyo Medical University
      Totigi, Tochigi, Japan
  • 1993–1996
    • CSU Mentor
      Long Beach, California, United States
  • 1995
    • London Research Institute
      Londinium, England, United Kingdom
  • 1985–1995
    • Sapienza University of Rome
      • • Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences
      • • Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science
      • • Department of Neuroscience, Mental Health and Sense Organs NESMOS
      Roma, Latium, Italy
  • 1994
    • Tuscia University
      Viterbo, Latium, Italy
  • 1990
    • It-Robotics
      Vicenza, Veneto, Italy