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Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache
BACKGROUND: Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH). Novel acute migraine-specific treatments are being develop...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412873/ https://www.ncbi.nlm.nih.gov/pubmed/32580575 http://dx.doi.org/10.1177/0333102420920006 |
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author | Rau, Jill C Navratilova, Edita Oyarzo, Janice Johnson, Kirk W Aurora, Sheena K Schwedt, Todd J Dodick, David W Porreca, Frank |
author_facet | Rau, Jill C Navratilova, Edita Oyarzo, Janice Johnson, Kirk W Aurora, Sheena K Schwedt, Todd J Dodick, David W Porreca, Frank |
author_sort | Rau, Jill C |
collection | PubMed |
description | BACKGROUND: Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH). Novel acute migraine-specific treatments are being developed. However, because the mechanism(s) underlying medication overuse headache are not well understood, it is difficult to predict whether any particular acute medication will induce MOH in susceptible individuals. LY573144 (lasmiditan), a 5-HT(1F) receptor agonist, has recently been shown to be effective in the acute treatment of migraine in phase 3 trials. The aim of this study is to determine whether frequent administration of lasmiditan induces behaviors consistent with MOH in a pre-clinical rat model. METHODS: Sprague Dawley rats were administered six doses of lasmiditan (10 mg/kg), sumatriptan (10 mg/kg), or sterile water orally over 2 weeks and cutaneous allodynia was evaluated regularly in the periorbital and hindpaw regions using von Frey filaments. Testing continued until mechanosensitivity returned to baseline levels. Rats were then submitted to bright light stress (BLS) or nitric oxide (NO) donor administration and were again evaluated for cutaneous allodynia in the periorbital and hindpaw regions hourly for 5 hours. RESULTS: Both lasmiditan and sumatriptan exhibited comparable levels of drug-induced cutaneous allodynia in both the periorbital and hindpaw regions, which resolved after cessation of drug administration. Both lasmiditan and sumatriptan pre-treatment resulted in cutaneous allodynia that was evoked by either BLS or NO donor. CONCLUSIONS: In a pre-clinical rat model of MOH, oral lasmiditan, like sumatriptan, induced acute transient cutaneous allodynia in the periorbital and hindpaw regions that after resolution could be re-evoked by putative migraine triggers. These results suggest that lasmiditan has the capacity to induce MOH through persistent latent peripheral and central sensitization mechanisms. |
format | Online Article Text |
id | pubmed-7412873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-74128732020-08-19 Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache Rau, Jill C Navratilova, Edita Oyarzo, Janice Johnson, Kirk W Aurora, Sheena K Schwedt, Todd J Dodick, David W Porreca, Frank Cephalalgia Original Articles BACKGROUND: Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH). Novel acute migraine-specific treatments are being developed. However, because the mechanism(s) underlying medication overuse headache are not well understood, it is difficult to predict whether any particular acute medication will induce MOH in susceptible individuals. LY573144 (lasmiditan), a 5-HT(1F) receptor agonist, has recently been shown to be effective in the acute treatment of migraine in phase 3 trials. The aim of this study is to determine whether frequent administration of lasmiditan induces behaviors consistent with MOH in a pre-clinical rat model. METHODS: Sprague Dawley rats were administered six doses of lasmiditan (10 mg/kg), sumatriptan (10 mg/kg), or sterile water orally over 2 weeks and cutaneous allodynia was evaluated regularly in the periorbital and hindpaw regions using von Frey filaments. Testing continued until mechanosensitivity returned to baseline levels. Rats were then submitted to bright light stress (BLS) or nitric oxide (NO) donor administration and were again evaluated for cutaneous allodynia in the periorbital and hindpaw regions hourly for 5 hours. RESULTS: Both lasmiditan and sumatriptan exhibited comparable levels of drug-induced cutaneous allodynia in both the periorbital and hindpaw regions, which resolved after cessation of drug administration. Both lasmiditan and sumatriptan pre-treatment resulted in cutaneous allodynia that was evoked by either BLS or NO donor. CONCLUSIONS: In a pre-clinical rat model of MOH, oral lasmiditan, like sumatriptan, induced acute transient cutaneous allodynia in the periorbital and hindpaw regions that after resolution could be re-evoked by putative migraine triggers. These results suggest that lasmiditan has the capacity to induce MOH through persistent latent peripheral and central sensitization mechanisms. SAGE Publications 2020-06-24 2020-08 /pmc/articles/PMC7412873/ /pubmed/32580575 http://dx.doi.org/10.1177/0333102420920006 Text en © International Headache Society 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Rau, Jill C Navratilova, Edita Oyarzo, Janice Johnson, Kirk W Aurora, Sheena K Schwedt, Todd J Dodick, David W Porreca, Frank Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache |
title | Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache |
title_full | Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache |
title_fullStr | Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache |
title_full_unstemmed | Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache |
title_short | Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache |
title_sort | evaluation of ly573144 (lasmiditan) in a preclinical model of medication overuse headache |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412873/ https://www.ncbi.nlm.nih.gov/pubmed/32580575 http://dx.doi.org/10.1177/0333102420920006 |
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