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2. Once-monthly galcanezumab for the prevention of migraine in adults: an evidence-based descriptive review and potential place in therapy

Author

Lupi C, Guerzoni S, Negro A, and Benemei S

Subjects
calcitonin gene-related peptide, headache, LY2951742, monoclonal antibody prophylaxis, Therapeutics. Pharmacology, RM1-950
Abstract

Chiara Lupi,1 Simona Guerzoni,2 Andrea Negro,3 Silvia Benemei1 1Headache Centre, Careggi University Hospital, Department of Health Sciences, University of Florence, Florence, Italy; 2Medical Toxicology Unit, Headache and Drug Abuse Centre, Department of Biomedical, Metabolic and Neural Sciences, University of Modena e Reggio Emilia, Modena, Italy; 3Department of Clinical and Molecular Medicine, Regional Referral Headache Centre, Sant’Andrea Hospital, Sapienza University, Rome Abstract: In the last 15 years relevant efforts have been made to demonstrate that calcitonin gene-related peptide (CGRP) antagonism is a valuable and druggable mechanism for treatment or prevention of migraine. Galcanezumab is one of the antibodies developed and studied to prevent migraine by targeting CGRP. The scope of this review is to report data currently available on galcanezumab. According to available data, galcanezumab is safe and efficacious in preventing migraine in episodic migraine patients, also reducing disability and functional impairment due to the disorder. In September 2018, galcanezumab was approved in the USA for the prevention of migraine in adults. The placement of galcanezumab into the current therapeutic scenario will be a revolution for migraine patients, and probably in a less near future also for patients affected by other primary headaches. Keywords: calcitonin gene-related peptide, headache, LY2951742, monoclonal antibody prophylaxis, CGRP

Published
2019

7. Mental pain and pain-proneness in migraine subjects: Results from the PAINMIG cohort-study

Author

Cosci F., Svicher A., Mansueto G., Benemei S., Chiarugi A., De Cesaris F., Guidi J., Zipfel S., Cosci F., Svicher A., Mansueto G., Benemei S., Chiarugi A., De Cesaris F., Guidi J., and Zipfel S.

Subjects
psychological distress, migraine, DCPR, mental pain, pain-pronene
Abstract

Background. Pain has been qualified under four categories: nociception, perception of pain, suffering, and pain behaviors. Most of the literature on migraine has devoted attention to the first two. The aim of the present cohort study was to investigate patients with migraine enrolled at a tertiary care unit to study and mental pain and identify potential risk factors for migraine. Methods: An observational cross-sectional study was carried out on patients with chronic migraine (CM), episodic migraine (EM), and healthy subjects (HS). The three groups were matched for age and sex. A comprehensive assessment of migraine disability, pain, psychiatric disorders, psychosomatic syndromes, depressive and anxious symptoms, euthymia, psychosocial variables, mental pain, and pain proneness was performed. Results: Three hundred subjects were enrolled (100 CM, 100 EM, 100 HS). Based on the multiple regression analyses, those presenting pain-proneness (social impairment: OR=3.59, 95%CI 1.14.-11.29; depressive symptoms: OR=3.82, 95%CI 1.74-8.41) were more likely to be CM than HS. Those with higher levels of pain-proneness (social impairment: OR=4.04, 95%CI 1.60-10.22; depressive symptoms: OR=2.02, 95%CI 1.26-3.24) were more likely to be EM than HS. Those presenting higher levels of mental pain were more likely to be CM than EM (OR=1.45, 95%CI 1.02-2.07). Conclusion: Migraine is an unpleasant sensory and emotional experience associated with psychosocial manifestations which might contribute to the level of suffering of the individuals. Mental pain resulted to be the variable which most differentiated chronic from episodic migraine individuals.

Published
2021

10. Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study

Author

Brinkman, D, Tichelaar, J, Mokkink, L, Christiaens, T, Likic, R, Maciulaitis, R, Costa, J, Sanz, E, Maxwell, S, Richir, M, Van, A, Michiel A., L, Kostadinova, I, Ganeva, M, Atanasova, I, Gatchev, E, Stavreva, G, Vitezic, D, Matanovic, S, Wozniak, G, Nicolaou, P, Urbanek, K, Slanar, O, Kmonickova, E, Demlova, R, Bergmann, T, Damkier, P, Kalda, A, Huupponen, R, Backman, J, Drici, M, Deplanque, D, Molimard, M, Toussirot, E, Pers, Y, Bertin, P, Laviolle, B, Jeunne, C, Saulnier, P, Chamontin, B, Roustit, M, Orlikowski, D, Simon, N, Dequin, P, Angoulvant, T, Bolbrinker, J, Wojnowski, L, Cascorbi, I, Müller, F, Müller, S, Schwaninger, M, Neumann, J, Stümpel, F, Regenthal, R, Fuhr, U, Thürmann, P, Eirini, A, Papaioannidou, P, Kouvelas, D, Kolios, G, Riba, P, Kerins, D, Williams, D, Harnett, A, Spina, E, Fumagalli, G, Filippelli, A, Benemei, S, De Ponti, F, Cosentino, M, Locatelli, V, De Montis, M, Memo, M, Raschi, E, Purvina, S, Gulbinovic, J, Mifsud, J, Keijsers, K, Rissmann, R, Dumont, G, van Rosse, F, Spigset, O, Opdal, M, Braszko, J, Mirowska-Guzel, D, Broncel, M, Kocic, I, Sousa, M, Monteiro, E, Dima, L, Magyar, I, Conea, S, Buzoianu, A, Glasova, H, Tisonova, J, Glasa, J, Krzan, M, Saez-Penataro, J, de Abajo Iglesias, F, Capella, D, Figuerola, F, Sansuan, A, Lopez-Rico, M, Manso, G, Benitez, J, Lucena, M, Bernal, M, Cladellas, X, Hernandez, R, Pontes, C, Panagiotidis, G, Böttiger, Y, Wallerstedt, S, Eriksson, A, Desmeules, J, Krähenbühl, S, Plumb, R, Okorie, M, Wilson, K, Mckay, G, Sofat, R, Kapil, V, Whitfield, J, Thanacoody, R, Mir, F, Loke, Y, Schachter, M, O'Brien, L, Heep, A, Brinkman, David J, Tichelaar, Jelle, Mokkink, Lidwine B, Christiaens, Thierry, Likic, Robert, Maciulaitis, Romaldas, Costa, Joao, Sanz, Emilio J, Maxwell, Simon R, Richir, Milan C, van Agtmael, Michiel A. Lefebvre R, Kostadinova I, Ganeva M, Atanasova I, Gatchev E, Stavreva G, Vitezic D, Matanovic S, Wozniak G, Nicolaou P, Urbanek K, Slanar O, Kmonickova E, Demlova R, Bergmann T, Damkier P, Kalda A, Huupponen R, Backman J, Drici MD, Deplanque D, Molimard M, Toussirot E, Pers YM, Bertin P, Laviolle B, Jeunne CL, Saulnier PJ, Chamontin B, Roustit M, Orlikowski D, Simon N, Dequin PF, Angoulvant T, Bolbrinker J, Wojnowski L, Cascorbi I, Müller F, Müller S, Schwaninger M, Neumann J, Stümpel F, Regenthal R, Fuhr U, Thürmann P, Eirini A, Papaioannidou P, Kouvelas D, Kolios G, Riba P, Kerins D, Williams D, Harnett A, Spina E, Fumagalli G, Filippelli A, Benemei S, De Ponti F, Cosentino M, Locatelli V, De Montis MG, Memo M, Raschi E, Purvina S, Gulbinovic J, Mifsud J, Keijsers K, Rissmann R, Dumont G, van Rosse F, Spigset O, Opdal MS, Braszko J, Mirowska-Guzel D, Broncel M, Kocic I, Sousa MC, Monteiro E, Dima L, Magyar I, Conea S, Buzoianu A, Glasova H, Tisonova J, Glasa J, Krzan M, Saez-Penataro J, de Abajo Iglesias FJ, Capella D, Figuerola FAH, Sansuan AJC, Lopez-Rico M, Manso G, Benitez J, Lucena MI, Bernal ML, Cladellas XC, Hernandez RA, Pontes C, Panagiotidis G, Böttiger Y, Wallerstedt S, Eriksson A, Desmeules J, Krähenbühl S, Plumb R, Okorie M, Wilson K, McKay G, Sofat R, Kapil V, Whitfield J, Thanacoody R, Mir F, Loke Y, Schachter M, O'Brien L, Heep A, Brinkman, D, Tichelaar, J, Mokkink, L, Christiaens, T, Likic, R, Maciulaitis, R, Costa, J, Sanz, E, Maxwell, S, Richir, M, Van, A, Michiel A., L, Kostadinova, I, Ganeva, M, Atanasova, I, Gatchev, E, Stavreva, G, Vitezic, D, Matanovic, S, Wozniak, G, Nicolaou, P, Urbanek, K, Slanar, O, Kmonickova, E, Demlova, R, Bergmann, T, Damkier, P, Kalda, A, Huupponen, R, Backman, J, Drici, M, Deplanque, D, Molimard, M, Toussirot, E, Pers, Y, Bertin, P, Laviolle, B, Jeunne, C, Saulnier, P, Chamontin, B, Roustit, M, Orlikowski, D, Simon, N, Dequin, P, Angoulvant, T, Bolbrinker, J, Wojnowski, L, Cascorbi, I, Müller, F, Müller, S, Schwaninger, M, Neumann, J, Stümpel, F, Regenthal, R, Fuhr, U, Thürmann, P, Eirini, A, Papaioannidou, P, Kouvelas, D, Kolios, G, Riba, P, Kerins, D, Williams, D, Harnett, A, Spina, E, Fumagalli, G, Filippelli, A, Benemei, S, De Ponti, F, Cosentino, M, Locatelli, V, De Montis, M, Memo, M, Raschi, E, Purvina, S, Gulbinovic, J, Mifsud, J, Keijsers, K, Rissmann, R, Dumont, G, van Rosse, F, Spigset, O, Opdal, M, Braszko, J, Mirowska-Guzel, D, Broncel, M, Kocic, I, Sousa, M, Monteiro, E, Dima, L, Magyar, I, Conea, S, Buzoianu, A, Glasova, H, Tisonova, J, Glasa, J, Krzan, M, Saez-Penataro, J, de Abajo Iglesias, F, Capella, D, Figuerola, F, Sansuan, A, Lopez-Rico, M, Manso, G, Benitez, J, Lucena, M, Bernal, M, Cladellas, X, Hernandez, R, Pontes, C, Panagiotidis, G, Böttiger, Y, Wallerstedt, S, Eriksson, A, Desmeules, J, Krähenbühl, S, Plumb, R, Okorie, M, Wilson, K, Mckay, G, Sofat, R, Kapil, V, Whitfield, J, Thanacoody, R, Mir, F, Loke, Y, Schachter, M, O'Brien, L, Heep, A, Brinkman, David J, Tichelaar, Jelle, Mokkink, Lidwine B, Christiaens, Thierry, Likic, Robert, Maciulaitis, Romaldas, Costa, Joao, Sanz, Emilio J, Maxwell, Simon R, Richir, Milan C, van Agtmael, Michiel A. Lefebvre R, Kostadinova I, Ganeva M, Atanasova I, Gatchev E, Stavreva G, Vitezic D, Matanovic S, Wozniak G, Nicolaou P, Urbanek K, Slanar O, Kmonickova E, Demlova R, Bergmann T, Damkier P, Kalda A, Huupponen R, Backman J, Drici MD, Deplanque D, Molimard M, Toussirot E, Pers YM, Bertin P, Laviolle B, Jeunne CL, Saulnier PJ, Chamontin B, Roustit M, Orlikowski D, Simon N, Dequin PF, Angoulvant T, Bolbrinker J, Wojnowski L, Cascorbi I, Müller F, Müller S, Schwaninger M, Neumann J, Stümpel F, Regenthal R, Fuhr U, Thürmann P, Eirini A, Papaioannidou P, Kouvelas D, Kolios G, Riba P, Kerins D, Williams D, Harnett A, Spina E, Fumagalli G, Filippelli A, Benemei S, De Ponti F, Cosentino M, Locatelli V, De Montis MG, Memo M, Raschi E, Purvina S, Gulbinovic J, Mifsud J, Keijsers K, Rissmann R, Dumont G, van Rosse F, Spigset O, Opdal MS, Braszko J, Mirowska-Guzel D, Broncel M, Kocic I, Sousa MC, Monteiro E, Dima L, Magyar I, Conea S, Buzoianu A, Glasova H, Tisonova J, Glasa J, Krzan M, Saez-Penataro J, de Abajo Iglesias FJ, Capella D, Figuerola FAH, Sansuan AJC, Lopez-Rico M, Manso G, Benitez J, Lucena MI, Bernal ML, Cladellas XC, Hernandez RA, Pontes C, Panagiotidis G, Böttiger Y, Wallerstedt S, Eriksson A, Desmeules J, Krähenbühl S, Plumb R, Okorie M, Wilson K, McKay G, Sofat R, Kapil V, Whitfield J, Thanacoody R, Mir F, Loke Y, Schachter M, O'Brien L, and Heep A

Abstract

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired.

Published
2018

12. The Role of β-Blockers in Melanoma

Author

De Giorgi, V., Geppetti, P., Lupi, C., and Benemei, S.

Subjects
Adrenaline, Melanoma, Noradrenaline, Propranolol, β-adrenoceptors
Published
2020

13. Early experience of an infectious and tropical diseases unit during the coronavirus disease (COVID-19) pandemic, Florence, Italy, February to March 2020

Author

Lagi, F., Piccica, M., Graziani, L., Vellere, I., Botta, A., Tilli, M., Ottino, L., Borchi, B., Pozzi, M., Bartalesi, F., Mencarini, J., Spinicci, M., Zammarchi, L., Pieralli, F., Zagli, G., Nozzoli, C., Romagnoli, S., Bartoloni, A., Campolmi, I., Di Lauria, N., Millotti, G., Basile, G., Meli, M., Rogasi, P. G., Bartolozzi, D., Corsi, P., Mazzetti, M., Farese, A., Bresci, S., Cavallo, A., Trotta, M., Corti, G., Morettini, A., Poggesi, L., de Gaudio, A. R., Peris, A., Fontanari, P., Parronchi, P., Almerigogna, F., Annunziato, F., Liotta, F., Cosmi, L., Vultaggio, A., Matucci, A., Angileri, M., Ipponi, A., Cecchi, M., Benemei, S., Vannucchi, A. M., Matucci Cerinic, Marco, and Turco, L.

Subjects
0301 basic medicine, Male, Author's Correction, Epidemiology, COVID-19, Cohort, Florence, ICU, Italy, SARS-CoV-2, pandemic, Age Distribution, Aged, Betacoronavirus, Cannula, Cohort Studies, Comorbidity, Contact Tracing, Coronavirus Infections, Critical Care, Disease Outbreaks, Female, Humans, Intensive Care Units, Middle Aged, Patient Transfer, Pneumonia, Viral, Respiratory Care Units, Sex Distribution, Treatment Outcome, Coronavirus, Pandemics, Disease, medicine.disease_cause, law.invention, 0302 clinical medicine, law, Pandemic, Medicine, 030212 general & internal medicine, Intensive care unit, Rapid Communication, medicine.medical_specialty, 030106 microbiology, 03 medical and health sciences, Virology, business.industry, Public Health, Environmental and Occupational Health, Outbreak, Tropical disease, medicine.disease, Emergency medicine, business, Contact tracing
Abstract

We analysed the first 84 coronavirus disease (COVID-19) patients hospitalised in an infectious and tropical disease unit in Florence, Italy, over 30 days after the start of the COVID-19 outbreak in Italy. A 12% reduction in the rate of intensive care unit transfer was observed after the implementation of intensity care measures in the regular ward such as increasing the nurse/patient ratio, presence of critical care physicians and using high flow nasal cannulae oxygenation.

Published
2020

14. Persistent post-traumatic headache: a migrainous loop or not? The preclinical evidence

Author

Benemei, S. (Silvia), Labastida-Ramirez, A. (Alejandro), Abramova, E. (Ekaterina), Brunelli, N. (Nicoletta), Caronna, E. (Edoardo), Diana, P. (Paola), Gapeshin, R. (Roman), Hofacker, M.D. (Maxi Dana), Maestrini, I. (Ilaria), Pías, E.M. (Enrique Martínez), Mikulenka, P. (Petr), Tikhonova, O. (Olga), Martelletti, P. (Paolo), Maassen van den Brink, A. (Antoinette), Benemei, S. (Silvia), Labastida-Ramirez, A. (Alejandro), Abramova, E. (Ekaterina), Brunelli, N. (Nicoletta), Caronna, E. (Edoardo), Diana, P. (Paola), Gapeshin, R. (Roman), Hofacker, M.D. (Maxi Dana), Maestrini, I. (Ilaria), Pías, E.M. (Enrique Martínez), Mikulenka, P. (Petr), Tikhonova, O. (Olga), Martelletti, P. (Paolo), and Maassen van den Brink, A. (Antoinette)

Abstract

BACKGROUND: According to the International Classification of Headache Disorders 3, post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) is a secondary headache reported to have developed within 7 days from head injury, regaining consciousness following the head injury, or discontinuation of medication(s) impairing the ability to sense or report headache following the head injury. It is one of the most common secondary headache disorders, and it is defined as persistent when it lasts more than 3 months. MAIN BODY: Currently, due to the high prevalence of this disorder, several preclinical studies have been conducted using different animal models of mild TBI to reproduce conditions that engender PTH. Despite representing a simplification of a complex disorder and displaying different limitations concerning the human condition, animal models are still a mainstay to study in vivo the mechanisms of PTH and have provided valuable insight into the pathophysiology and possible treatment strategies. Different models reproduce different types of trauma and have been ideated in order to ensure maximal proximity to the human condition and optimal experimental reproducibility. CONCLUSION: At present, despite its high prevalence, PTH is not entirely understood, and the differential contribution of pathophysiological mechanisms, also observed in other conditions like migraine, has to be clarified. Although facing limitations, animal models are needed to improve understanding of PTH. The knowledge of currently available models is necessary to all researchers who want to investigate PTH and contribute to unravel its mechanisms.

Published
2020
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15. Persistent post-traumatic headache: A migrainous loop or not? The clinical evidence

Author

Labastida-Ramirez, A. (Alejandro), Benemei, S. (Silvia), Albanese, M. (Maria), D'Amico, A. (Antonina), Grillo, G. (Giovanni), Grosu, O. (Oxana), Ertem, D.H. (Devrimsel Harika), Mecklenburg, J. (Jasper), Fedorova, E.P. (Elena Petrovna), Řehulka, P. (Pavel), Di Cola, F.S. (Francesca Schiano), Lopez, J.T. (Javier Trigo), Vashchenko, N. (Nina), Maassen van den Brink, A. (Antoinette), Martelletti, P. (Paolo), Labastida-Ramirez, A. (Alejandro), Benemei, S. (Silvia), Albanese, M. (Maria), D'Amico, A. (Antonina), Grillo, G. (Giovanni), Grosu, O. (Oxana), Ertem, D.H. (Devrimsel Harika), Mecklenburg, J. (Jasper), Fedorova, E.P. (Elena Petrovna), Řehulka, P. (Pavel), Di Cola, F.S. (Francesca Schiano), Lopez, J.T. (Javier Trigo), Vashchenko, N. (Nina), Maassen van den Brink, A. (Antoinette), and Martelletti, P. (Paolo)

Abstract

Background: Headache is a common complication of traumatic brain injury. The International Headache Society defines post-traumatic headache as a secondary headache attributed to trauma or injury to the head that develops within seven days following trauma. Acute post-traumatic headache resolves after 3 months, but persistent post-traumatic headache usually lasts much longer and accounts for 4% of all secondary headache disorders. Main body: The clinical features of post-traumatic headache after traumatic brain injury resemble various types of primary headaches and the most frequent are migraine-like or tension-type-like phenotypes. The neuroimaging studies that have compared persistent post-traumatic headache and migraine found different structural and functional brain changes, although migraine and post-traumatic headache may be clinically similar. Therapy of various clinical phenotypes of post-traumatic headache almost entirely mirrors the therapy of the corresponding primary headache and are currently based on expert opinion rather than scientific evidence. Pharmacologic therapies include both abortive and prophylactic agents with prophylaxis targeting comorbidities, especially impaired sleep and post-traumatic disorder. There are also effective options for non-pharmacologic therapy of post-traumatic headache, including cognitive-behavioral approaches, onabotulinum toxin injections, life-style considerations, etc. Conclusion: Notwithstanding some phenotypic similarities, persistent post-traumatic headache after traumatic brain injury, is considered a separate phenomenon from migraine but available data is inconclusive. High-quality studies are further required to investigate the pathophysiological mechanisms of this secondary headache, in order to identify new targets for treatment and to prevent disability.

Published
2020
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16. Persistent post-traumatic headache: a migrainous loop or not? The preclinical evidence

Author

Benemei, S, Labastida Ramirez, Alejandro, Abramova, E, Brunelli, N, Caronna, E, Diana, P, Gapeshin, R, Hofacker, MD, Maestrini, I, Pias, EM, Mikulenka, P, Tikhonova, O, Martelletti, P, Maassen van den Brink, Antoinette, Benemei, S, Labastida Ramirez, Alejandro, Abramova, E, Brunelli, N, Caronna, E, Diana, P, Gapeshin, R, Hofacker, MD, Maestrini, I, Pias, EM, Mikulenka, P, Tikhonova, O, Martelletti, P, and Maassen van den Brink, Antoinette

Published
2020

17. Persistent post-traumatic headache: a migrainous loop or not? The clinical evidence

Author

Labastida Ramirez, Alejandro, Benemei, S, Albanese, M, D'Amico, A, Grillo, G, Grosu, O, Ertem, DH, Mecklenburg, J, Fedorova, EP, Rehulka, P, di Cola, FS, Lopez, JT, Vashchenko, N, Maassen van den Brink, Antoinette, Martelletti, P, Ehf, SAS, Labastida Ramirez, Alejandro, Benemei, S, Albanese, M, D'Amico, A, Grillo, G, Grosu, O, Ertem, DH, Mecklenburg, J, Fedorova, EP, Rehulka, P, di Cola, FS, Lopez, JT, Vashchenko, N, Maassen van den Brink, Antoinette, Martelletti, P, and Ehf, SAS

Published
2020

19. Poor patient awareness and frequent misdiagnosis of migraine: findings from a large transcontinental cohort

Author

Viana, M., primary, Khaliq, F., additional, Zecca, C., additional, Figuerola, M. D. L., additional, Sances, G., additional, Di Piero, V., additional, Petolicchio, B., additional, Alessiani, M., additional, Geppetti, P., additional, Lupi, C., additional, Benemei, S., additional, Iannacchero, R., additional, Maggioni, F., additional, Jurno, M. E., additional, Odobescu, S., additional, Chiriac, E., additional, Marfil, A., additional, Brighina, F., additional, Barrientos Uribe, N., additional, Pérez Lago, C., additional, Bordini, C., additional, Lucchese, F., additional, Maffey, V., additional, Nappi, G., additional, Sandrini, G., additional, and Tassorelli, C., additional

Published
2019
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20. Migraine and cluster headache - the common link

Author

Vollesen, A.L. (Anne Luise), Benemei, S. (Silvia), Cortese, F. (Francesca), Labastida-Ramirez, A. (Alejandro), Marchese, F. (Francesca), Pellesi, L. (Lanfranco), Romoli, M. (Michele), Ashina, M. (Messoud), Lampl, C. (Christian), Vollesen, A.L. (Anne Luise), Benemei, S. (Silvia), Cortese, F. (Francesca), Labastida-Ramirez, A. (Alejandro), Marchese, F. (Francesca), Pellesi, L. (Lanfranco), Romoli, M. (Michele), Ashina, M. (Messoud), and Lampl, C. (Christian)

Abstract

Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.

Published
2018
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21. TRPA1/NOX in the soma of trigeminal ganglion neurons mediates migraine-related pain of glyceryl trinitrate in mice.

Author

Marone, IM, De Logu, F, Nassini, R, De Carvalho Goncalves, M, Benemei, S, Ferreira, J, Jain, P, Li Puma, S, Bunnett, NW, Geppetti, P, Materazzi, S, Marone, IM, De Logu, F, Nassini, R, De Carvalho Goncalves, M, Benemei, S, Ferreira, J, Jain, P, Li Puma, S, Bunnett, NW, Geppetti, P, and Materazzi, S

Abstract

Glyceryl trinitrate is administered as a provocative test for migraine pain. Glyceryl trinitrate causes prolonged mechanical allodynia in rodents, which temporally correlates with delayed glyceryl trinitrate-evoked migraine attacks in patients. However, the underlying mechanism of the allodynia evoked by glyceryl trinitrate is unknown. The proalgesic transient receptor potential ankyrin 1 (TRPA1) channel, expressed by trigeminal nociceptors, is sensitive to oxidative stress and is targeted by nitric oxide or its by-products. Herein, we explored the role of TRPA1 in glyceryl trinitrate-evoked allodynia. Systemic administration of glyceryl trinitrate elicited in the mouse periorbital area an early and transient vasodilatation and a delayed and prolonged mechanical allodynia. The systemic, intrathecal or local administration of selective enzyme inhibitors revealed that nitric oxide, liberated from the parent drug by aldehyde dehydrogenase 2 (ALDH2), initiates but does not maintain allodynia. The central and the final phases of allodynia were respectively associated with generation of reactive oxygen and carbonyl species within the trigeminal ganglion. Allodynia was absent in TRPA1-deficient mice and was reversed by TRPA1 antagonists. Knockdown of neuronal TRPA1 by intrathecally administered antisense oligonucleotide and selective deletion of TRPA1 from sensory neurons in Advillin-Cre; Trpa1fl/fl mice revealed that nitric oxide-dependent oxidative and carbonylic stress generation is due to TRPA1 stimulation, and resultant NADPH oxidase 1 (NOX1) and NOX2 activation in the soma of trigeminal ganglion neurons. Early periorbital vasodilatation evoked by glyceryl trinitrate was attenuated by ALDH2 inhibition but was unaffected by TRPA1 blockade. Antagonists of the calcitonin gene-related peptide receptor did not affect the vasodilatation but partially inhibited allodynia. Thus, although both periorbital allodynia and vasodilatation evoked by glyceryl trinitrate are initiated

Published
2018

22. Migraine and cluster headache - the common link

Author

Vollesen, AL, Benemei, S, Cortese, F, Labastida Ramirez, Alejandro, Marchese, F, Pellesi, L, Romoli, M, Ashina, M, Lampl, C, Vollesen, AL, Benemei, S, Cortese, F, Labastida Ramirez, Alejandro, Marchese, F, Pellesi, L, Romoli, M, Ashina, M, and Lampl, C

Published
2018

25. Poor patient awareness and frequent misdiagnosis of migraine: findings from a large transcontinental cohort.

Author

Viana, M., Khaliq, F., Zecca, C., Figuerola, M. D. L., Sances, G., Di Piero, V., Petolicchio, B., Alessiani, M., Geppetti, P., Lupi, C., Benemei, S., Iannacchero, R., Maggioni, F., Jurno, M. E., Odobescu, S., Chiriac, E., Marfil, A., Brighina, F., Barrientos Uribe, N., and Pérez Lago, C.

Subjects
TENSION headache, MIGRAINE, NECK pain, DIAGNOSTIC errors, CERVICAL vertebrae, MAGNETIC resonance imaging
Abstract

Background and purpose: Although migraine is the second most disabling condition worldwide, there is poor awareness of it. The objective was to assess the awareness of migraine and previous diagnostic and therapeutic consultations and treatments in a large international population of migraineurs. Methods: This was a multicentre study conducted in 12 headache centres in seven countries. Each centre recruited up to 100 patients referred for a first visit and diagnosed with migraine. Subjects were given a structured clinical questionnaire‐based interview about the perceptions of the type of headache they suffered from, its cause, previous diagnoses, investigations and treatments. Results: In all, 1161 patients completed the study. Twenty‐eight per cent of participants were aware that they suffered from migraine. Sixty‐four per cent called their migraine 'headache'; less commonly they used terms such as 'cervical pain' (4%), tension headache (3%) and sinusitis (1%). Eight per cent of general practitioners and 35% of specialists (of whom 51% were neurologists and/or headache specialists) consulted for migraine formulated the correct diagnosis. Before participating in the study, 50% of patients had undergone X‐ray, computed tomography and/or magnetic resonance imaging of the cervical spine and 76% underwent brain and/or cervical spine imaging for migraine. Twenty‐eight per cent of patients had received symptomatic migraine‐specific medications and 29% at least one migraine preventive medication. Conclusions: Although migraine is a very common disease, poor awareness of it amongst patients and physicians is still an issue in several countries. This highlights the importance of the promotion of migraine awareness to reduce its burden and limit direct and indirect costs and the risk of exposure to useless investigations. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Essential Competencies in Prescribing: A First European Cross-Sectional Study Among 895 Final-Year Medical Students

Author

Brinkman, D. J., Tichelaar, J., Schutte, T., Benemei, S., Böttiger, Ylva, Chamontin, B., Christiaens, T., Likic, R., Maciulaitis, R., Marandi, T., Monteiro, E. C., Papaioannidou, P., Pers, Y. M., Pontes, C., Raskovic, A., Regenthal, R., Sanz, E. J., Tamba, B. I., Wilson, K., de Vries, T. P., Richir, M. C., van Agtmael, M. A., Brinkman, D. J., Tichelaar, J., Schutte, T., Benemei, S., Böttiger, Ylva, Chamontin, B., Christiaens, T., Likic, R., Maciulaitis, R., Marandi, T., Monteiro, E. C., Papaioannidou, P., Pers, Y. M., Pontes, C., Raskovic, A., Regenthal, R., Sanz, E. J., Tamba, B. I., Wilson, K., de Vries, T. P., Richir, M. C., and van Agtmael, M. A.

Abstract

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

Published
2017
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29. Triptans and CGRP blockade – impact on the cranial vasculature

Author

Benemei, S. (Silvia), Cortese, F. (Francesca), Labastida-Ramírez, A. (Alejandro), Marchese, F. (Francesca), Pellesi, L. (Lanfranco), Romoli, M. (Michele), Vollesen, A.L. (Anne Luise), Lampl, C. (Christian), Ashina, M. (Messoud), Benemei, S. (Silvia), Cortese, F. (Francesca), Labastida-Ramírez, A. (Alejandro), Marchese, F. (Francesca), Pellesi, L. (Lanfranco), Romoli, M. (Michele), Vollesen, A.L. (Anne Luise), Lampl, C. (Christian), and Ashina, M. (Messoud)

Abstract

The trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D receptors (triptans) and less than fifteen after the proof of concept of the gepant class of CGRP receptor antagonists, we are still a long way from understanding their precise site and mode of action in migraine. The effect on cranial vasculature is relevant, because all specific anti-migraine drugs and migraine pharmacological triggers may act in perivascular space. This review reports the effects of triptans and CGRP blocking molecules on cranial vasculature in humans, focusing on their specific relevance to migraine treatment.

Published
2017
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30. Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice.

Author

De Logu, F, Nassini, R, Materazzi, S, Carvalho Gonçalves, M, Nosi, D, Rossi Degl'Innocenti, D, Marone, IM, Ferreira, J, Li Puma, S, Benemei, S, Trevisan, G, Souza Monteiro de Araújo, D, Patacchini, R, Bunnett, NW, Geppetti, P, De Logu, F, Nassini, R, Materazzi, S, Carvalho Gonçalves, M, Nosi, D, Rossi Degl'Innocenti, D, Marone, IM, Ferreira, J, Li Puma, S, Benemei, S, Trevisan, G, Souza Monteiro de Araújo, D, Patacchini, R, Bunnett, NW, and Geppetti, P

Abstract

It is known that transient receptor potential ankyrin 1 (TRPA1) channels, expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1 is also expressed in Schwann cells. We found that in mice with partial sciatic nerve ligation, TRPA1 silencing in nociceptors attenuated mechanical allodynia, without affecting macrophage infiltration and oxidative stress, whereas TRPA1 silencing in Schwann cells reduced both allodynia and neuroinflammation. Activation of Schwann cell TRPA1 evoked NADPH oxidase 1 (NOX1)-dependent H2O2 release, and silencing or blocking Schwann cell NOX1 attenuated nerve injury-induced macrophage infiltration, oxidative stress and allodynia. Furthermore, the NOX2-dependent oxidative burst, produced by macrophages recruited to the perineural space activated the TRPA1-NOX1 pathway in Schwann cells, but not TRPA1 in nociceptors. Schwann cell TRPA1 generates a spatially constrained gradient of oxidative stress, which maintains macrophage infiltration to the injured nerve, and sends paracrine signals to activate TRPA1 of ensheathed nociceptors to sustain mechanical allodynia.

Published
2017

33. The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives

Author

Nassini, R, Fusi, C, Materazzi, S, Coppi, E, Tuccinardi, Tiziano, Marone, Im, De Logu, F, Preti, D, Tonello, R, Chiarugi, A, Patacchini, R, Geppetti, P, and Benemei, S.

Subjects
Male, Nociception, Dipyrone, Pain, Nerve Tissue Proteins, Concise guide, agranulocytosis, NO, Rats, Sprague-Dawley, Transient Receptor Potential Channels, Animals, Humans, metamizol, Pyrazolones, TRPA1 Cation Channel, TRPC Cation Channels, neuropathic pain, Analgesics, neurogenic inflammation, food and beverages, Research Papers, cold, inhibition, Mice, Inbred C57BL, pharmacology, activation, protein, HEK293 Cells, Hyperalgesia, Calcium Channels
Abstract

Although still used by hundreds of millions of people worldwide, the mechanism of the analgesic action of the pyrazolone derivatives (PDs), dipyrone, propyphenazone and antipyrine remains unknown. The transient receptor potential ankyrin 1 (TRPA1) channel, expressed by nociceptors, is emerging as a major pain transduction pathway. We hypothesized that PDs target the TRPA1 channel and by this mechanism produce their analgesic effect.Calcium responses and currents were studied in cultured TRPA1-expressing rodent dorsal root ganglion neurons and human cells. Acute nociception and mechanical hypersensitivity were investigated in naïve and genetically manipulated mice.Pyrazolone and PDs selectively inhibited calcium responses and currents in TRPA1-expressing cells and acute nocifensor responses in mice evoked by reactive channel agonists (allyl isothiocyanate, acrolein and H2 O2 ). In line with recent results obtained with TRPA1 antagonists and TRPA1 gene deletion, the two most largely used PDs, dipyrone and propyphenazone, attenuated TRPA1-mediated nociception and mechanical allodynia in models of inflammatory and neuropathic pain (formalin, carrageenan, partial sciatic nerve ligation and the chemotherapeutic drug, bortezomib). Notably, dipyrone and propyphenazone attenuated carrageenan-evoked mechanical allodynia, without affecting PGE2 levels. The main metabolites of PDs did not target TRPA1 and did not affect TRPA1-dependent nociception and allodynia.Evidence that in rodents the nociceptive/hyperalgesic effect produced by TRPA1 activation is blocked by PDs suggests that a similar pathway is attenuated by PDs in humans and that TRPA1 antagonists could be novel analgesics, devoid of the adverse haematological effects of PDs.

Published
2015

44. Anaphylaxis during the first course of high-dose methotrexate: a case report and literature review.

Author

Pugi, A., Benemei, S., Vietri, M., Tondo, A., Calvani, A. M., Mugelli, A., Vannacci, A., and Lapi, F.

Subjects
*ANAPHYLAXIS, *ANTINEOPLASTIC agents, *BONE tumors, *DRUG allergy, *DOSE-effect relationship in pharmacology, *METHOTREXATE, *OSTEOSARCOMA
Abstract

Summary What is known and Objective: Methotrexate (MTX) is widely used in the management of paediatric cancer with a generally favourable benefit/risk profile. We report an unusual adverse drug reaction with the first course of high-dose MTX in a paediatric patient and review the literature for similar cases. Case summary: An 11-year-old boy with small-cell osteoblastic osteosarcoma in the lower limb experienced a case of life-threatening anaphylaxis during the first course of high-dose MTX. The adverse event occurred during the first course, likely due to an immune-mediated mechanism. We postulate that prior antineoplastic treatment might have contributed to the immune response to MTX. What is new and Conclusion: Given that this reaction has rarely been reported, we discuss the present case with a review of other similar cases. Further studies are needed to substantiate this 'signal alarm' for serious MTX-related hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

Published
2012
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45. The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system.

Author

Nassini R, Materazzi S, Vriens J, Prenen J, Benemei S, De Siena G, la Marca G, Andrè E, Preti D, Avonto C, Sadofsky L, Di Marzo V, De Petrocellis L, Dussor G, Porreca F, Taglialatela-Scafati O, Appendino G, Nilius B, Geppetti P, and Nassini, Romina

Abstract

The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile constituent of the leaves of Umbellularia californica, has irritating properties, and is a reactive molecule that rapidly binds thiols. Thus, we hypothesized that umbellulone stimulates the transient receptor potential ankyrin 1 channel in a subset of peptidergic, nocioceptive neurons, activating the trigeminovascular system via this mechanism. Umbellulone, from µM to sub-mM concentrations, selectively stimulated transient receptor potential ankyrin 1-expressing HEK293 cells and rat trigeminal ganglion neurons, but not untransfected cells or neurons in the presence of the selective transient receptor potential ankyrin 1 antagonist, HC-030031. Umbellulone evoked a calcium-dependent release of calcitonin gene-related peptide from rodent trigeminal nerve terminals in the dura mater. In wild-type mice, umbellulone elicited excitation of trigeminal neurons and released calcitonin gene-related peptide from sensory nerve terminals. These two responses were absent in transient receptor potential ankyrin 1 deficient mice. Umbellulone caused nocioceptive behaviour after stimulation of trigeminal nerve terminals in wild-type, but not transient receptor potential ankyrin 1 deficient mice. Intranasal application or intravenous injection of umbellulone increased rat meningeal blood flow in a dose-dependent manner; a response selectively inhibited by systemic administration of transient receptor potential ankyrin 1 or calcitonin gene-related peptide receptor antagonists. These data indicate that umbellulone activates, through a transient receptor potential ankyrin 1-dependent mechanism, the trigeminovascular system, thereby causing nocioceptive responses and calcitonin gene-related peptide release. Pharmacokinetics of umbellulone, given by either intravenous or intranasal administration, suggest that transient receptor potential ankyrin 1 stimulation, which eventually results in meningeal vasodilatation, may be produced via two different pathways, depending on the dose. Transient receptor potential ankyrin 1 activation may either be caused directly by umbellulone, which diffuses from the nasal mucosa to perivascular nerve terminals in meningeal vessels, or by stimulation of trigeminal endings within the nasal mucosa and activation of reflex pathways. Transient receptor potential ankyrin 1 activation represents a plausible mechanism for Umbellularia californica-induced headache. Present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde and others that are known to be headache triggers and recently identified as transient receptor potential ankyrin 1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain. [ABSTRACT FROM AUTHOR]

Published
2012
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48. Pleasant natural scent with unpleasant effects: Cluster headache-like attacks triggered by Umbellularia californica.

Author

Benemei, S., Appendino, G., and Geppetti, P.

Subjects
*ODORS, *CLUSTER headache, *UMBELLULARIA californica, *ITALIANS, *GARDENERS, *DISEASES, *PHYSIOLOGY
Abstract

Umbellularia californica, a shrub or tree indigenous to southwestern Oregon and northern California, is commonly known as headache tree, probably because it is reported that its scent can cause headache. Here, we report the case of a 69-year-old Italian gardener, affected during his young adult age by cluster headache, who, 10 years from his last cluster episode, developed shorter-lasting cluster-like headache attacks after and at any time he was exposed to U. californica scent. The present case indicates that, even though endogenous mechanisms causing the cluster headache were no longer present, susceptibility to exogenous triggers remains active in this patient, and suggests that identification of the constituent(s) of U. californica responsible for triggering cluster headache-like attacks may help in the understanding of the hitherto elusive mechanism of cluster headache. [ABSTRACT FROM AUTHOR]

Published
2010
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49. Correction to: A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches.

Author

on behalf of the European Headache Federation School of Advanced Studies (EHF-SAS), García-Azorin, D., Speranza, M. L., Marini, V., Negro, A., Benemei, S., Barloese, M., Yamani, N., Messina, L. M., Peeters, I., Ferilli, M. A. N., and Ovchinnikov, D.

Subjects
PRIMARY headache disorders, THERAPEUTICS
Abstract

Following publication of the original article [1], we have been notified that the name of author five was spelled incorrectly as M. Ferrili, when the correct spelling is MAN Ferilli. [ABSTRACT FROM AUTHOR]

Published
2019
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