Cargando…
Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain
The antineoplastic agent oxaliplatin induces an acute hypersensitivity evoked by cold that has been suggested to be due to sensitized central and peripheral neurons. Rodent-based preclinical studies have suggested numerous treatments for the alleviation of oxaliplatin-induced neuropathic pain, but f...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954874/ https://www.ncbi.nlm.nih.gov/pubmed/29854035 http://dx.doi.org/10.1155/2018/1630709 |
_version_ | 1783323604195213312 |
---|---|
author | Hama, Aldric Natsume, Takahiro Ogawa, Shin'ya Higo, Noriyuki Hayashi, Ikuo Takamatsu, Hiroyuki |
author_facet | Hama, Aldric Natsume, Takahiro Ogawa, Shin'ya Higo, Noriyuki Hayashi, Ikuo Takamatsu, Hiroyuki |
author_sort | Hama, Aldric |
collection | PubMed |
description | The antineoplastic agent oxaliplatin induces an acute hypersensitivity evoked by cold that has been suggested to be due to sensitized central and peripheral neurons. Rodent-based preclinical studies have suggested numerous treatments for the alleviation of oxaliplatin-induced neuropathic pain, but few have demonstrated robust clinical efficacy. One issue is that current understanding of the pathophysiology of oxaliplatin-induced neuropathic pain is primarily based on rodent models, which might not entirely recapitulate the clinical pathophysiology. In addition, there is currently no objective physiological marker for pain that could be utilized to objectively indicate treatment efficacy. Nonhuman primates are phylogenetically and neuroanatomically similar to humans; thus, disease mechanism in nonhuman primates could reflect that of clinical oxaliplatin-induced neuropathy. Cold-activated pain-related brain areas in oxaliplatin-treated macaques were attenuated with duloxetine, the only drug that has demonstrated clinical efficacy for chemotherapy-induced neuropathic pain. By contrast, drugs that have not demonstrated clinical efficacy in oxaliplatin-induced neuropathic pain did not reduce brain activation. Thus, a nonhuman primate model could greatly enhance understanding of clinical pathophysiology beyond what has been obtained with rodent models and, furthermore, brain activation could serve as an objective marker of pain and therapeutic efficacy. |
format | Online Article Text |
id | pubmed-5954874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-59548742018-05-31 Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain Hama, Aldric Natsume, Takahiro Ogawa, Shin'ya Higo, Noriyuki Hayashi, Ikuo Takamatsu, Hiroyuki Pain Res Manag Review Article The antineoplastic agent oxaliplatin induces an acute hypersensitivity evoked by cold that has been suggested to be due to sensitized central and peripheral neurons. Rodent-based preclinical studies have suggested numerous treatments for the alleviation of oxaliplatin-induced neuropathic pain, but few have demonstrated robust clinical efficacy. One issue is that current understanding of the pathophysiology of oxaliplatin-induced neuropathic pain is primarily based on rodent models, which might not entirely recapitulate the clinical pathophysiology. In addition, there is currently no objective physiological marker for pain that could be utilized to objectively indicate treatment efficacy. Nonhuman primates are phylogenetically and neuroanatomically similar to humans; thus, disease mechanism in nonhuman primates could reflect that of clinical oxaliplatin-induced neuropathy. Cold-activated pain-related brain areas in oxaliplatin-treated macaques were attenuated with duloxetine, the only drug that has demonstrated clinical efficacy for chemotherapy-induced neuropathic pain. By contrast, drugs that have not demonstrated clinical efficacy in oxaliplatin-induced neuropathic pain did not reduce brain activation. Thus, a nonhuman primate model could greatly enhance understanding of clinical pathophysiology beyond what has been obtained with rodent models and, furthermore, brain activation could serve as an objective marker of pain and therapeutic efficacy. Hindawi 2018-05-02 /pmc/articles/PMC5954874/ /pubmed/29854035 http://dx.doi.org/10.1155/2018/1630709 Text en Copyright © 2018 Aldric Hama et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Hama, Aldric Natsume, Takahiro Ogawa, Shin'ya Higo, Noriyuki Hayashi, Ikuo Takamatsu, Hiroyuki Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain |
title | Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain |
title_full | Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain |
title_fullStr | Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain |
title_full_unstemmed | Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain |
title_short | Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain |
title_sort | gaps in understanding mechanism and lack of treatments: potential use of a nonhuman primate model of oxaliplatin-induced neuropathic pain |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954874/ https://www.ncbi.nlm.nih.gov/pubmed/29854035 http://dx.doi.org/10.1155/2018/1630709 |
work_keys_str_mv | AT hamaaldric gapsinunderstandingmechanismandlackoftreatmentspotentialuseofanonhumanprimatemodelofoxaliplatininducedneuropathicpain AT natsumetakahiro gapsinunderstandingmechanismandlackoftreatmentspotentialuseofanonhumanprimatemodelofoxaliplatininducedneuropathicpain AT ogawashinya gapsinunderstandingmechanismandlackoftreatmentspotentialuseofanonhumanprimatemodelofoxaliplatininducedneuropathicpain AT higonoriyuki gapsinunderstandingmechanismandlackoftreatmentspotentialuseofanonhumanprimatemodelofoxaliplatininducedneuropathicpain AT hayashiikuo gapsinunderstandingmechanismandlackoftreatmentspotentialuseofanonhumanprimatemodelofoxaliplatininducedneuropathicpain AT takamatsuhiroyuki gapsinunderstandingmechanismandlackoftreatmentspotentialuseofanonhumanprimatemodelofoxaliplatininducedneuropathicpain |