Cargando…

Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models

Cancer-induced bone pain is one of the most severe types of pathological pain, which often occurs in patients with advanced prostate, breast, and lung cancer. It is of great significance to improve the therapies of cancer-induced bone pain due to the opioids’ side effects including addiction, sedati...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Shu-Ping, Sun, Jia, Zhou, Ya-Qun, Cao, Fei, Braun, Cody, Luo, Fang, Ye, Da-Wei, Tian, Yu-Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096675/
https://www.ncbi.nlm.nih.gov/pubmed/30027795
http://dx.doi.org/10.1177/1744806918793232
_version_ 1783348149117517824
author Chen, Shu-Ping
Sun, Jia
Zhou, Ya-Qun
Cao, Fei
Braun, Cody
Luo, Fang
Ye, Da-Wei
Tian, Yu-Ke
author_facet Chen, Shu-Ping
Sun, Jia
Zhou, Ya-Qun
Cao, Fei
Braun, Cody
Luo, Fang
Ye, Da-Wei
Tian, Yu-Ke
author_sort Chen, Shu-Ping
collection PubMed
description Cancer-induced bone pain is one of the most severe types of pathological pain, which often occurs in patients with advanced prostate, breast, and lung cancer. It is of great significance to improve the therapies of cancer-induced bone pain due to the opioids’ side effects including addiction, sedation, pruritus, and vomiting. Sinomenine, a traditional Chinese medicine, showed obvious analgesic effects on a rat model of chronic inflammatory pain, but has never been proven to treat cancer-induced bone pain. In the present study, we investigated the analgesic effect of sinomenine after tumor cell implantation and specific cellular mechanisms in cancer-induced bone pain. Our results indicated that single administration of sinomenine significantly and dose-dependently alleviated mechanical allodynia in rats with cancer-induced bone pain and the effect lasted for 4 h. After tumor cell implantation, the protein levels of phosphorylated-Janus family tyrosine kinase 2 (p-JAK2), phosphorylated-signal transducers and activators of transcription 3 (p-STAT3), phosphorylated-Ca2+/calmodulin-dependent protein kinase II (p-CAMKII), and phosphorylated-cyclic adenosine monophosphate response element-binding protein (p-CREB) were persistently up-regulated in the spinal cord horn. Chronic intraperitoneal treatment with sinomenine markedly suppressed the activation of microglia and effectively inhibited the expression of JAK2/STAT3 and CAMKII/CREB signaling pathways. We are the first to reveal that up-regulation of microglial JAK2/STAT3 pathway are involved in the development and maintenance of cancer-induced bone pain. Moreover, our investigation provides the first evidence that sinomenine alleviates cancer-induced bone pain by inhibiting microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades.
format Online
Article
Text
id pubmed-6096675
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-60966752018-08-23 Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models Chen, Shu-Ping Sun, Jia Zhou, Ya-Qun Cao, Fei Braun, Cody Luo, Fang Ye, Da-Wei Tian, Yu-Ke Mol Pain Research Article Cancer-induced bone pain is one of the most severe types of pathological pain, which often occurs in patients with advanced prostate, breast, and lung cancer. It is of great significance to improve the therapies of cancer-induced bone pain due to the opioids’ side effects including addiction, sedation, pruritus, and vomiting. Sinomenine, a traditional Chinese medicine, showed obvious analgesic effects on a rat model of chronic inflammatory pain, but has never been proven to treat cancer-induced bone pain. In the present study, we investigated the analgesic effect of sinomenine after tumor cell implantation and specific cellular mechanisms in cancer-induced bone pain. Our results indicated that single administration of sinomenine significantly and dose-dependently alleviated mechanical allodynia in rats with cancer-induced bone pain and the effect lasted for 4 h. After tumor cell implantation, the protein levels of phosphorylated-Janus family tyrosine kinase 2 (p-JAK2), phosphorylated-signal transducers and activators of transcription 3 (p-STAT3), phosphorylated-Ca2+/calmodulin-dependent protein kinase II (p-CAMKII), and phosphorylated-cyclic adenosine monophosphate response element-binding protein (p-CREB) were persistently up-regulated in the spinal cord horn. Chronic intraperitoneal treatment with sinomenine markedly suppressed the activation of microglia and effectively inhibited the expression of JAK2/STAT3 and CAMKII/CREB signaling pathways. We are the first to reveal that up-regulation of microglial JAK2/STAT3 pathway are involved in the development and maintenance of cancer-induced bone pain. Moreover, our investigation provides the first evidence that sinomenine alleviates cancer-induced bone pain by inhibiting microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades. SAGE Publications 2018-08-14 /pmc/articles/PMC6096675/ /pubmed/30027795 http://dx.doi.org/10.1177/1744806918793232 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.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 Research Article
Chen, Shu-Ping
Sun, Jia
Zhou, Ya-Qun
Cao, Fei
Braun, Cody
Luo, Fang
Ye, Da-Wei
Tian, Yu-Ke
Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models
title Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models
title_full Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models
title_fullStr Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models
title_full_unstemmed Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models
title_short Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models
title_sort sinomenine attenuates cancer-induced bone pain via suppressing microglial jak2/stat3 and neuronal camkii/creb cascades in rat models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096675/
https://www.ncbi.nlm.nih.gov/pubmed/30027795
http://dx.doi.org/10.1177/1744806918793232
work_keys_str_mv AT chenshuping sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels
AT sunjia sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels
AT zhouyaqun sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels
AT caofei sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels
AT brauncody sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels
AT luofang sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels
AT yedawei sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels
AT tianyuke sinomenineattenuatescancerinducedbonepainviasuppressingmicroglialjak2stat3andneuronalcamkiicrebcascadesinratmodels