Research Research unitsChrOnic PAin Laboratory _ CoPaL

ChrOnic PAin Laboratory _ CoPaL

Awarded the European Research Council Advanced Grant, 2019-2024
‘Schwann Cell Options for chronic Pain Eradication’ – SCOPE

 Scientific coordinator: Pierangelo Geppetti, MD

Professor of Clinical Pharmacology at the Department of Health Sciences and the Biomedical School of the University of Florence
Chief of the Clinical Unit - Headache Center and Clinical Pharmacology, University Hospital of Careggi – Florence 
Past-President of the Italian Society for the Study of Headaches
Editor of Pain, Molecular Pain, The Journal of Headache and Pain, Handbook of Experimental Pharmacology; Past editor Physiological Reviews, British Journal of Pharmacology

 

Research Interest

Pierangelo Geppetti is a clinician and basic scientist studying the mechanisms and treatments of chronic pain, with a special focus on migraine and related primary headaches. Pierangelo’s lab seeks to understand the role of the feed-forward pathway which entails transient receptor potential (TRP) channels in Schwann cells and their ability to generate oxidative stress to signal chronic pain in models of inflammatory, neuropathic, cancer, and migraine pain.  The lab also seeks to discover new medicines for the treatment of chronic pain. 

 

Representative Publications

431 original and review articles 
h-Index of 81, Total citations >23,000 (Scopus).

 

Members 

Romina Nassini, PhD, 

Associate Professor of Clinical Pharmacology at the Department of Health Sciences and the Biomedical School of the University of Florence 

Romina Nassini is a basic scientist whose research interest focuses on the identification of new activators and inhibitors of the TRP channels and the molecular and translational aspects of these mechanisms. Romina has contributed to the identification of pathways by which inflammatory mediators signal to sensory nerves by gating receptors and channels, to cause pain in different models of cancer-related pain, including those due to the use of chemotherapeutic drugs, and models of pain due to cancer growth. More recently, Romina has contributed substantially to the identification of a novel mechanism (the TRPA1/NOX1 pathway) in Schwann cells, which, sustaining neuroinflammation, signals chronic neuropathic pain. 

93 original and review articles, 6 book chapters e 6 conference proceedings. 

h-Index 36, Total citations > 4700 (Scopus)

Complete listing available on the University of Florence site. 

 

Francesco De Logu, PhD, 

Scientific Researcher at the Department of Health Sciences and the Biomedical School of the University of Florence 

Francesco De Logu is a basic scientist who has opened a new area of investigation in the lab by coupling pharmacology and bio-imaging. Francesco, using unique expertise in several in vitro (molecular and cellular biology and immunohistochemistry) and in vivo (mastering complex models of diseases in mice) techniques, has markedly contributed to the understanding of the cellular and molecular basis of neuroinflammatory pathways that sustain chronic pain. Editor in Experimental Pharmacology and Drug Discovery, Frontiers in Pharmacology.

57 original and review articles, 4 book chapters.

n-Index 19, Total citations 1005 (Scopus)

Complete listing available on the University of Florence site. 

 

Other lab members

Daniel Souza Monteiro De Araujo, PhD, Research Fellow
Gaetano De Siena, PharmD, Research Fellow
Matilde Marini, BS, PhD student 
Lorenzo Landini, PhD, Research Fellow
Mustafa Titiz, BS, PhD student 
Luigi Francesco Iannone, MD, Research Fellow

 

Selected papers in the last 10 years

1. De Logu F, Nassini R, Hegron A, Landini L, Jensen DD, Latorre R, Ding J, Marini M, Souza Monteiro de Araujo D, Ramírez-Garcia P, Whittaker M, Retamal J, Titiz M, Innocenti A, Davis TP, Veldhuis N, Schmidt BL, Bunnett NW, Geppetti P. Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice. Nat Commun. 2022 13(1):646.
2. De Logu F, Marini M, Landini L, Souza Monteiro de Araujo D, Bartalucci N, Trevisan G, Bruno G, Marangoni M, Schmidt BL, Bunnett NW, Geppetti P, Nassini R. Peripheral Nerve Resident Macrophages and Schwann Cells Mediate Cancer-induced Pain. Cancer Res. 2021 26:3326.2020.
3. Romagnoli S, Peris A, De Gaudio AR, Geppetti P. SARS-CoV-2 and COVID-19: From the Bench to the Bedside. Physiol Rev. 2020 100:1455-1466.
4. De Logu F, De Prá SD, de David Antoniazzi CT, Kudsi SQ, Ferro PR, Landini L, Rigo FK, de Bem Silveira G, Silveira PCL, Oliveira SM, Marini M, Mattei G, Ferreira J, Geppetti P, Nassini R, Trevisan G. Macrophages and Schwann cell TRPA1 mediate chronic allodynia in a mouse model of complex regional pain syndrome type I. Brain Behav Immun. 2020 88:535-546.
5. De Logu F, Li Puma S, Landini L, Portelli F, Innocenti A, de Araújo DSM, Janal MN, Patacchini R, Bunnett NW, Geppetti P, Nassini R. Schwann cells expressing nociceptive channel TRPA1 orchestrate ethanol-evoked neuropathic pain in mice. J Clin Invest. 2019 129:5424-5441.
6. De Logu F, Trevisan G, Marone IM, Coppi E, Padilha Dalenogare D, Titiz M, Marini M, Landini L, Souza Monteiro de Araujo D, Li Puma S, Materazzi S, De Siena G, Geppetti P, Nassini R. Oxidative stress mediates thalidomide-induced pain by targeting peripheral TRPA1 and central TRPV4. BMC Biol. 2020 18:197.
7. 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. TRPA1/NOX in the soma of trigeminal ganglion neurons mediates migraine-related pain of glyceryl trinitrate in mice. Brain. 2018 Jul 6. 141(8):2312-2328.
8. 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. Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice. Nat Commun. 2017 8:1887.
9. Benemei S, De Logu F, Li Puma S, Marone IM, Coppi E, Ugolini F, Liedtke W, Pollastro F, Appendino G, Geppetti P, Materazzi S, Nassini R. The anti-migraine component of butterbur extracts, isopetasin, desensitizes peptidergic nociceptors by acting on TRPA1 cation channel. Br J Pharmacol. 2017 174:2897-2911.
10. Jensen DD, Lieu T, Halls ML, Veldhuis NA, Imlach WL, Mai QN, Poole DP, Quach T, Aurelio L, Conner J, Herenbrink CK, Barlow N, Simpson JS, Scanlon MJ, Graham B, McCluskey A, Robinson PJ, Escriou V, Nassini R, Materazzi S, Geppetti P, Hicks GA, Christie MJ, Porter CJH, Canals M, Bunnett NW. Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief. Sci Transl Med. 2017 31 (392).
11. Yarwood RE, Imlach WL, Lieu T, Veldhuis NA, Jensen DD, Klein Herenbrink C, Aurelio L, Cai Z, Christie MJ, Poole DP, Porter CJH, McLean P, Hicks GA, Geppetti P, Halls ML, Canals M, Bunnett NW. Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission. Proc Natl Acad Sci U S A. 2017 114:12309-12314
12. De Logu F, Tonello R, Materazzi S, Nassini R, Fusi C, Coppi E, Li Puma S, Marone IM, Sadofsky LR, Morice AM, Susini T, Terreni A, Moneti G, Di Tommaso M, Geppetti P, Benemei S. TRPA1 mediates aromatase inhibitor-evoked pain by the aromatase substrate androstenedione. Cancer Res. 2016 Dec 6:7024-7035.
13. Trevisan G, Benemei S, Materazzi S, De Logu F, De Siena G, Fusi C, Fortes Rossato M, Coppi E, Marone IM, Ferreira J, Geppetti P, Nassini R. TRPA1 mediates trigeminal neuropathic pain in mice downstream of monocytes/macrophages and oxidative stress. Brain. 2016 139:1361-77.
14. Nassini R, Fusi C, Materazzi S, Coppi E, Tuccinardi T, Marone IM, De Logu F, Preti D, Tonello R, Chiarugi A, Patacchini R, Geppetti P, Benemei S. The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives. Br J Pharmacol. 2015 172:3397-411
15. Geppetti P, Veldhuis NA, Lieu T, Bunnett NW. G Protein-Coupled Receptors: Dynamic Machines for Signaling Pain and Itch. Neuron. 2015 18;88:635-49.
16. Fusi C, Materazzi S, Benemei S, Coppi E, Trevisan G, Marone IM, Minocci D, De Logu F, Tuccinardi T, Di Tommaso MR, Susini T, Moneti G, Pieraccini G, Geppetti P, Nassini R. Steroidal and non-steroidal third-generation aromatase inhibitors induce pain-like symptoms via TRPA1. Nat Commun. 2014 8;5:5736.
17. 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, Nassini R,. The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system. Brain 2012  135:376-90.
18. Steinhoff MS, von Mentzer B, Geppetti P, Pothoulakis C, Bunnett NW. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev. 2014 94:265-301
19. Lieu T, Jayaweera G, Zhao P, Poole DP, Jensen D, Grace M, McIntyre P, Bron R, Wilson YM, Krappitz M, Haerteis S, Korbmacher C, Steinhoff MS, Nassini R, Materazzi S, Geppetti P, Corvera CU, Bunnett NW. The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice. Gastroenterology. 2014 147:1417-28.
20. Benemei S, Fusi C, Trevisan G, Geppetti P. The TRPA1 channel in migraine mechanism and treatment. Br J Pharmacol. 2014 171:2552-67.
21. Nassini R, Materazzi S, Benemei S, Geppetti P. The TRPA1 channel in inflammatory and neuropathic pain and migraine. Rev Physiol Biochem Pharmacol. 2014;167:1-43.
22. Alemi F, Kwon E, Poole DP, Lieu T, Lyo V, Cattaruzza F, Cevikbas F, Steinhoff M, Nassini R, Materazzi S, Guerrero-Alba R, Valdez-Morales E, Cottrell GS, Schoonjans K, Geppetti P, Vanner SJ, Bunnett NW, Corvera CU. The TGR5 receptor mediates bile acid-induced itch and analgesia. J Clin Invest. 2013 123:1513-30.
23. Trevisan G, Materazzi S, Fusi C, Altomare A, Aldini G, Lodovici M, Patacchini R, Geppetti P, Nassini R. Novel therapeutic strategy to prevent chemotherapy-induced persistent sensory neuropathy by TRPA1 blockade. Cancer Res. 2013 73:3120-31.
24. Tozzi A, de Iure A, Di Filippo M, Costa C, Caproni S, Pisani A, Bonsi P, Picconi B, Cupini LM, Materazzi S, Geppetti P, Sarchielli P, Calabresi P. Critical role of calcitonin gene-related peptide receptors in cortical spreading depression. Proc Natl Acad Sci U S A. 2012 109(46):18985-90.
25. 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, Nassini R,. The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system. Brain 2012  135:376-90.