Publications by authors named "H O Handwerker"

188 Publications

Robert F. Schmidt Ph.D., Prof. Dr. med. D. Sc. h.c. 1932-2017 Facets of a life for science.

Eur J Pain 2018 02;22(2):207-213

Institut für Physiologie and Exp. Pathophysiologie, Universität Erlangen-Nürnberg, Erlangen, Germany.

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http://dx.doi.org/10.1002/ejp.1170DOI Listing
February 2018

Ensuring transparency and minimization of methodologic bias in preclinical pain research: PPRECISE considerations.

Pain 2016 Apr;157(4):901-909

Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Department of Anatomy, University of California San Francisco, San Francisco, CA, USA Department of Psychology and Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA Pain Research, Department of Surgery and Cancer, Imperial College, London, United Kingdom Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom Departments of Anesthesiology, Neurology, and Psychiatry, University of Rochester, Rochester, NY, USA Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Biostatistics, Harvard University, Boston, MA, USA Department of Anesthesiology, University of Rochester, Rochester, NY, USA Clinical and Rehabilitative Medicine Research Program, United States Army Medical Research and Materiel Command, Fort Detrick, MD, USA Department of Physiology and Pathophysiology, Friedrich-Alexander Universität, Erlangen-Nürnberg, Germany Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom Eli Lilly & Co., Indianapolis, IN, USA Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA Neuroscience Discovery Research, Eli Lilly & Co., Indianapolis, IN, USA Policy Department, Wellcome Trust, London, United Kingdom Departments of Medicine and Oral Surgery, University of California San Francisco, San Francisco, CA, USA National Centre for Replacement, Refinement & Reduction of Animals in Research, London, United Kingdom Kent, United Kingdom Department of Biostatistics and Computational Biology and Department of Neurology, University of Rochester, Rochester, NY, USA Neurorestoration group, King's College, London, United Kingdom School of Behavioral and Brain Sciences, University of Texas at Dallas, TX, USA Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Palo Alto, CA, USA Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA Office of Career and Professional Development, University of California San Francisco, San Francisco, CA, USA Faculty of Dentistry & Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA Discovery Research, Purdue Pharma, Cranbury, NJ, USA.

There is growing concern about lack of scientific rigor and transparent reporting across many preclinical fields of biological research. Poor experimental design and lack of transparent reporting can result in conscious or unconscious experimental bias, producing results that are not replicable. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration sponsored a consensus meeting of the Preclinical Pain Research Consortium for Investigating Safety and Efficacy (PPRECISE) Working Group. International participants from universities, funding agencies, government agencies, industry, and a patient advocacy organization attended. Reduction of publication bias, increasing the ability of others to faithfully repeat experimental methods, and increased transparency of data reporting were specifically discussed. Parameters deemed essential to increase confidence in the published literature were clear, specific reporting of an a priori hypothesis and definition of primary outcome measure. Power calculations and whether measurement of minimal meaningful effect size to determine these should be a core component of the preclinical research effort provoked considerable discussion, with many but not all agreeing. Greater transparency of reporting should be driven by scientists, journal editors, reviewers, and grant funders. The conduct of high-quality science that is fully reported should not preclude novelty and innovation in preclinical pain research, and indeed, any efforts that curtail such innovation would be misguided. We believe that to achieve the goal of finding effective new treatments for patients with pain, the pain field needs to deal with these challenging issues.
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http://dx.doi.org/10.1097/j.pain.0000000000000458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794131PMC
April 2016

[Physiology of pain].

Schmerz 2015 Oct;29(5):522-30

Institut für Physiologie und Pathophysiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstr. 17, 91054, Erlangen, Deutschland.

Pain research is based broadly on physiological disciplines and its development follows the methodological progress of the era, from classical psychophysiology to electrophysiological investigations at peripheral and central nociceptive systems, single cells and ion channels to modern imaging of nociceptive processing. Physiological pain research in Germany has long been part of an interdisciplinary research network extending beyond all political boundaries, and this situation has continued since molecular techniques started to dominate all biomedical research. Current scientific questions, such as intracellular nociceptive signal mechanisms, interactions with other physiological systems including the immune system, or the genetic basis of epidemic and chronic pain diseases can only be solved interdisciplinary and with international collaboration.
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http://dx.doi.org/10.1007/s00482-015-0052-yDOI Listing
October 2015

Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7.

Pain 2015 Sep;156(9):1637-1646

Department of Physiology and Pathophysiology, University of Erlangen, Erlangen, Germany Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway Department of Clinical Neurophysiology, University of Uppsala, Uppsala, Sweden Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway Department of Rheumatology, Skin and Infectious Diseases, Oslo University Hospital, Oslo, Norway Department of Vascular Surgery, Oslo University Hospital, Oslo, Norway AstraZeneca Translational Science Centre, Department of Clinical Neuroscience, Karolinska Institutet, Sweden AstraZeneca R&D, Macclesfield, United Kingdom Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA Department of Anesthesiology Mannheim, Heidelberg University, Heidelberg, Germany.

Seven patients diagnosed with erythromelalgia (EM) were investigated by microneurography to record from unmyelinated nerve fibers in the peroneal nerve. Two patients had characterized variants of sodium channel Nav1.7 (I848T, I228M), whereas no mutations of coding regions of Navs were found in 5 patients with EM. Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the patients with EM showed spontaneous activity. In the patient with mutation I848T, all nociceptors, but not sympathetic efferents, displayed enhanced early subnormal conduction in the velocity recovery cycles and the expected late subnormality was reversed to supranormal conduction. The larger hyperpolarizing shift of activation might explain the difference to the I228M mutation. Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the patient carrying the I848T mutation, confirming in human subjects that the presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant channels. The characteristic pattern of changes in conduction velocity observed in the patient with the I848T gain-of function mutation in Nav1.7 could be explained by axonal depolarization and concomitant inactivation of Nav1.7. If this were true, activity-dependent hyperpolarization would reverse inactivation of Nav1.7 and account for the supranormal CV. This mechanism might explain normal pain thresholds under resting conditions.
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http://dx.doi.org/10.1097/j.pain.0000000000000229DOI Listing
September 2015

Cerebral Networks Linked to Itch-related Sensations Induced by Histamine and Capsaicin.

Acta Derm Venereol 2015 Jul;95(6):645-52

Department of Physiology and Pathophysiology, FAU Erlangen/Nuremberg, Universitaetsstr. 17, DE-91054 Erlangen, Germany.

This functional magnetic resonance imaging (fMRI) study explored the central nervous processing of itch induced by histamine and capsaicin, delivered via inactivated cowhage spicules, and the influence of low-dose naltrexone. Scratch bouts were delivered at regular intervals after spicule insertion in order temporarily to suppress the itch. At the end of each trial the subjects rated their itch and scratch-related sensations. Stepwise multiple regression analyses were employed for identifying cerebral networks contributing to the intensities of "itching", "burning", "stinging", "pricking" and "itch relief by scratching". In the capsaicin experiments a network for "burning" was identified, which included the posterior insula, caudate and putamen. In the histamine experiments networks for "itching" and "itch relief" were found, which included operculum, hippocampus and amygdala. Naltrexone generally reduced fMRI activation and the correlations between fMRI signal and ratings. Furthermore, scratching was significantly less pleasant under naltrexone.
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http://dx.doi.org/10.2340/00015555-2006DOI Listing
July 2015