About the Authors

Mark F. Bird

Affiliation Department of Cardiovascular Sciences, University of Leicester, Division of Anaesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom

Maria Camilla Cerlesi

Contributed equally to this work with: Maria Camilla Cerlesi, Mark Brown

Affiliation Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy

Mark Brown

Contributed equally to this work with: Maria Camilla Cerlesi, Mark Brown

Affiliation Department of Cardiovascular Sciences, University of Leicester, Division of Anaesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom

Davide Malfacini

Affiliation Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy

Vanessa Vezzi

Affiliation Department of Pharmacology, Istituto Superiore di Sanità, Rome, 00161, Italy

Paola Molinari

Affiliation Department of Pharmacology, Istituto Superiore di Sanità, Rome, 00161, Italy

Laura Micheli

Affiliation Department of Neuroscience, Psychology, Drug Research and Child Health—Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy

Lorenzo Di Cesare Mannelli

Affiliation Department of Neuroscience, Psychology, Drug Research and Child Health—Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy

Carla Ghelardini

Affiliation Department of Neuroscience, Psychology, Drug Research and Child Health—Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy

Remo Guerrini

Affiliation Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, Ferrara, Italy

Girolamo Calò

Affiliation Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy

David G. Lambert

dgl3@le.ac.uk

Affiliation Department of Cardiovascular Sciences, University of Leicester, Division of Anaesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, Leicester, LE2 7LX, United Kingdom

Competing Interests

DGL held a consultancy with Grunenthal GmbH and can confirm this does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. For the avoidance of doubt the consultancy with Grunenthal was declared for reasons of probity. They had no input to this work either intellectual or financial and other than a general interest in the data there will be no direct financial gain.

Author Contributions

Conceived and designed the experiments: MFB MCC MB DM VV PM LM LDCM CG RG GC DGL. Performed the experiments: MFB MCC MB DM VV PM LM LDCM CG. Analyzed the data: MFB MCC MB DM VV PM LM LDCM CG RG GC DGL. Wrote the paper: MFB MCC MB DM VV PM LM LDCM CG RG GC DGL.