Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain

Diener, Suzie; Breimhorst, Markus; Vogt, Th.; Krämer, Heidrun H.; Drummond, Peter D.; Geber, Christian; Birklein, Frank

doi:10.1002/ejp.1031

Cited by 2 publications

(2 citation statements)

References 46 publications

(98 reference statements)

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“…Non‐replicated studies reported positive results with hydrocortisone (Michaux et al., 2012 ), intrathecal adenosine (Eisenach et al., 2002 ), and epidural or intrathecal clonidine (Eisenach et al., , 1998 , 2000 ). Inconsistent results were observed with botulinum toxin (Diener et al., 2017 ; Gazerani et al., 2006 ). The tricyclic antidepressants amitriptyline and desipramine failed to modify 2HA in two studies (Eisenach et al., 1997 ; Wallace et al., 2002 ).…”

Section: Resultsmentioning

confidence: 90%

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

Quesada

Kostenko

et al. 2021

European Journal of Pain

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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 surrogateThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Resultsmentioning

confidence: 90%

“…toxin (Diener et al, 2017;Gazerani et al, 2006). The tricyclic antidepressants amitriptyline and desipramine failed to modify 2HA in two studies (Eisenach et al, 1997;.…”

Section: Ha Areamentioning

confidence: 95%

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

Quesada

Kostenko

et al. 2021

European Journal of Pain

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A data science approach to the selection of most informative readouts of the human intradermal capsaicin pain model to assess pregabalin effects

Lötsch

Walter

Zunftmeister

et al. 2019

Basic Clin Pharma Tox

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Persistent and, in particular, neuropathic pain is a major healthcare problem with still insufficient pharmacological treatment options. This triggered research activities aimed at finding analgesics with a novel mechanism of action. Results of these efforts will need to pass through the phases of drug development, in which experimental human pain models are established components e.g. implemented as chemical hyperalgesia induced by capsaicin. We aimed at ranking the various readouts of a human capsaicin–based pain model with respect to the most relevant information about the effects of a potential reference analgesic. In a placebo‐controlled, randomized cross‐over study, seven different pain‐related readouts were acquired in 16 healthy individuals before and after oral administration of 300 mg pregabalin. The sizes of the effect on pain induced by intradermal injection of capsaicin were quantified by calculating Cohen's d. While in four of the seven pain‐related parameters, pregabalin provided a small effect judged by values of Cohen's d exceeding 0.2, an item categorization technique implemented as computed ABC analysis identified the pain intensities in the area of secondary hyperalgesia and of allodynia as the most suitable parameters to quantify the analgesic effects of pregabalin. Results of this study provide further support for the ability of the intradermal capsaicin pain model to show analgesic effects of pregabalin. Results can serve as a basis for the designs of studies where the inclusion of this particular pain model and pregabalin is planned.

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Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain

Cited by 2 publications

References 46 publications

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

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

A data science approach to the selection of most informative readouts of the human intradermal capsaicin pain model to assess pregabalin effects

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