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Human surrogate models of central sensitization: A critical review and practical guide

BACKGROUND: As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often charac...

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Autores principales: Quesada, Charles, Kostenko, Anna, Ho, Idy, Leone, Caterina, Nochi, Zahra, Stouffs, Alexandre, Wittayer, Matthias, Caspani, Ombretta, Brix Finnerup, Nanna, Mouraux, André, Pickering, Gisèle, Tracey, Irene, Truini, Andrea, Treede, Rolf‐Detlef, Garcia‐Larrea, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360051/
https://www.ncbi.nlm.nih.gov/pubmed/33759294
http://dx.doi.org/10.1002/ejp.1768
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author Quesada, Charles
Kostenko, Anna
Ho, Idy
Leone, Caterina
Nochi, Zahra
Stouffs, Alexandre
Wittayer, Matthias
Caspani, Ombretta
Brix Finnerup, Nanna
Mouraux, André
Pickering, Gisèle
Tracey, Irene
Truini, Andrea
Treede, Rolf‐Detlef
Garcia‐Larrea, Luis
author_facet Quesada, Charles
Kostenko, Anna
Ho, Idy
Leone, Caterina
Nochi, Zahra
Stouffs, Alexandre
Wittayer, Matthias
Caspani, Ombretta
Brix Finnerup, Nanna
Mouraux, André
Pickering, Gisèle
Tracey, Irene
Truini, Andrea
Treede, Rolf‐Detlef
Garcia‐Larrea, Luis
author_sort Quesada, Charles
collection PubMed
description BACKGROUND: As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission. DATA TREATMENT: We therefore performed a systematic literature review (PubMed‐Medline, Cochrane, WoS, ClinicalTrials) and semi‐quantitative meta‐analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury. RESULTS: From an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low‐ or high‐frequency electrical stimulation, thermode‐induced heat‐injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower. The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development. CONCLUSIONS: While there is no single “optimal” model of central sensitization, the range of validated and easy‐to‐use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data. SIGNIFICANCE: Being able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogate models has proven to have excellent predictive validity: they respond to clinically active medications and do not respond to clinically inactive medications, including some that worked in animals but failed in the clinics. They should therefore inform basic research for new drug development.
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spelling pubmed-83600512021-08-17 Human surrogate models of central sensitization: A critical review and practical guide Quesada, Charles Kostenko, Anna Ho, Idy Leone, Caterina Nochi, Zahra Stouffs, Alexandre Wittayer, Matthias Caspani, Ombretta Brix Finnerup, Nanna Mouraux, André Pickering, Gisèle Tracey, Irene Truini, Andrea Treede, Rolf‐Detlef Garcia‐Larrea, Luis Eur J Pain Review Articles BACKGROUND: As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission. DATA TREATMENT: We therefore performed a systematic literature review (PubMed‐Medline, Cochrane, WoS, ClinicalTrials) and semi‐quantitative meta‐analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury. RESULTS: From an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low‐ or high‐frequency electrical stimulation, thermode‐induced heat‐injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower. The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development. CONCLUSIONS: While there is no single “optimal” model of central sensitization, the range of validated and easy‐to‐use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data. SIGNIFICANCE: Being able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogate models has proven to have excellent predictive validity: they respond to clinically active medications and do not respond to clinically inactive medications, including some that worked in animals but failed in the clinics. They should therefore inform basic research for new drug development. John Wiley and Sons Inc. 2021-05-08 2021-08 /pmc/articles/PMC8360051/ /pubmed/33759294 http://dx.doi.org/10.1002/ejp.1768 Text en © 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC® https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Articles
Quesada, Charles
Kostenko, Anna
Ho, Idy
Leone, Caterina
Nochi, Zahra
Stouffs, Alexandre
Wittayer, Matthias
Caspani, Ombretta
Brix Finnerup, Nanna
Mouraux, André
Pickering, Gisèle
Tracey, Irene
Truini, Andrea
Treede, Rolf‐Detlef
Garcia‐Larrea, Luis
Human surrogate models of central sensitization: A critical review and practical guide
title Human surrogate models of central sensitization: A critical review and practical guide
title_full Human surrogate models of central sensitization: A critical review and practical guide
title_fullStr Human surrogate models of central sensitization: A critical review and practical guide
title_full_unstemmed Human surrogate models of central sensitization: A critical review and practical guide
title_short Human surrogate models of central sensitization: A critical review and practical guide
title_sort human surrogate models of central sensitization: a critical review and practical guide
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360051/
https://www.ncbi.nlm.nih.gov/pubmed/33759294
http://dx.doi.org/10.1002/ejp.1768
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