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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hama, Aldric, Natsume, Takahiro, Ogawa, Shin'ya, Higo, Noriyuki, Hayashi, Ikuo, Takamatsu, Hiroyuki
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