β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis

Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment and so far no effective drug is available for treatment of the serious side effect. Previous studies have demonstrated β2-adrenoreceptor (ADRB2) agonists can attenuate neuropathic pain. However, the ro...

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Autores principales:	Nan Chen, Meng-Meng Ge, Dan-Yang Li, Xiao-Mei Wang, Dai-Qiang Liu, Da-Wei Ye, Yu-Ke Tian, Ya-Qun Zhou, Jian-Ping Chen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Paclitaxel Neuropathic pain Formoterol β2-adrenoreceptor Mitochondrial biogenesis PGC-1α Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e077944fe2614b26aa15925d8a136ef8
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spelling	oai:doaj.org-article:e077944fe2614b26aa15925d8a136ef82021-11-14T04:29:50Zβ2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis0753-332210.1016/j.biopha.2021.112331https://doaj.org/article/e077944fe2614b26aa15925d8a136ef82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S075333222101115Xhttps://doaj.org/toc/0753-3322Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment and so far no effective drug is available for treatment of the serious side effect. Previous studies have demonstrated β2-adrenoreceptor (ADRB2) agonists can attenuate neuropathic pain. However, the role of ADRB2 in paclitaxel -induced neuropathic pain (PINP) remains unclear. In this study, we investigated the effect of formoterol, a long-acting ADRB2 agonist, and related mechanisms in PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to evaluate mechanical allodynia. Western blot was used to examine the expression of ADRB2, peroxisome proliferator–activated receptor coactivator-1α (PGC-1α), nuclear respiratory factors 1 (NRF1) and mitochondrial transcription factor A (TFAM) and the immunofluorescence was to detect the cellular localization of ADRB2 and PGC-1α in the spinal cord. Moreover, we measured mitochondrial DNA (mtDNA) copy number by qPCR. In our study, formoterol attenuated established PINP and delayed the onset of PINP. Formoterol restored ADRB2 expression as well as mtDNA copy number and PGC-1α, NRF1, and TFAM protein expression, which are major genes involved in mitochondrial biogenesis, in the spinal cord of PINP rats. Moreover, we found the analgesic effect of formoterol against PINP was partially abolished by PGC-1α inhibitor SR-18292. Collectively, these results demonstrated the activation of ADRB2 with formoterol ameliorates PINP at least partially through induction of mitochondrial biogenesis.Nan ChenMeng-Meng GeDan-Yang LiXiao-Mei WangDai-Qiang LiuDa-Wei YeYu-Ke TianYa-Qun ZhouJian-Ping ChenElsevierarticlePaclitaxelNeuropathic painFormoterolβ2-adrenoreceptorMitochondrial biogenesisPGC-1αTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112331- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Paclitaxel Neuropathic pain Formoterol β2-adrenoreceptor Mitochondrial biogenesis PGC-1α Therapeutics. Pharmacology RM1-950
spellingShingle	Paclitaxel Neuropathic pain Formoterol β2-adrenoreceptor Mitochondrial biogenesis PGC-1α Therapeutics. Pharmacology RM1-950 Nan Chen Meng-Meng Ge Dan-Yang Li Xiao-Mei Wang Dai-Qiang Liu Da-Wei Ye Yu-Ke Tian Ya-Qun Zhou Jian-Ping Chen β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis
description	Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment and so far no effective drug is available for treatment of the serious side effect. Previous studies have demonstrated β2-adrenoreceptor (ADRB2) agonists can attenuate neuropathic pain. However, the role of ADRB2 in paclitaxel -induced neuropathic pain (PINP) remains unclear. In this study, we investigated the effect of formoterol, a long-acting ADRB2 agonist, and related mechanisms in PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to evaluate mechanical allodynia. Western blot was used to examine the expression of ADRB2, peroxisome proliferator–activated receptor coactivator-1α (PGC-1α), nuclear respiratory factors 1 (NRF1) and mitochondrial transcription factor A (TFAM) and the immunofluorescence was to detect the cellular localization of ADRB2 and PGC-1α in the spinal cord. Moreover, we measured mitochondrial DNA (mtDNA) copy number by qPCR. In our study, formoterol attenuated established PINP and delayed the onset of PINP. Formoterol restored ADRB2 expression as well as mtDNA copy number and PGC-1α, NRF1, and TFAM protein expression, which are major genes involved in mitochondrial biogenesis, in the spinal cord of PINP rats. Moreover, we found the analgesic effect of formoterol against PINP was partially abolished by PGC-1α inhibitor SR-18292. Collectively, these results demonstrated the activation of ADRB2 with formoterol ameliorates PINP at least partially through induction of mitochondrial biogenesis.
format	article
author	Nan Chen Meng-Meng Ge Dan-Yang Li Xiao-Mei Wang Dai-Qiang Liu Da-Wei Ye Yu-Ke Tian Ya-Qun Zhou Jian-Ping Chen
author_facet	Nan Chen Meng-Meng Ge Dan-Yang Li Xiao-Mei Wang Dai-Qiang Liu Da-Wei Ye Yu-Ke Tian Ya-Qun Zhou Jian-Ping Chen
author_sort	Nan Chen
title	β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis
title_short	β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis
title_full	β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis
title_fullStr	β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis
title_full_unstemmed	β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis
title_sort	β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e077944fe2614b26aa15925d8a136ef8
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β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis

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