Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel

Huang, Ya-Kun; Lu, Yu-Gang; Zhao, Xin; Zhang, Jingbing; Zhang, Fengming; Chen, Yong; Bi, Ling-Bo; Gu, Jiahui; Jiang, Zuo-Jie; Wu, Xiaoman; Li, Qingyi; Liu, Yanli; Shen, Jianxin; Liu, Xingjun

doi:10.1111/bph.15284

Cited by 28 publications

(23 citation statements)

References 55 publications

(112 reference statements)

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“…The DRG contains neurons, satellite cells, and macrophages. Iba1 is a specific marker for activated macrophages or microglia and is used to label macrophages in the DRG, but not for satellite cells [ 6 , 28 , 29 , 30 , 31 ]. Our immunofluorescence staining studies showed that macrophages in the DRG surround relatively larger neurons, which is similar to previous reports [ 6 , 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…Iba1 is a specific marker for activated macrophages or microglia and is used to label macrophages in the DRG, but not for satellite cells [ 6 , 28 , 29 , 30 , 31 ]. Our immunofluorescence staining studies showed that macrophages in the DRG surround relatively larger neurons, which is similar to previous reports [ 6 , 30 ]. In Wistar rats, few Iba1-marked cells were found around CGRP-marked neurons, while most Iba1-marked cells were primarily found around NF200-marked neurons at 6 weeks ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

“…Macrophages in the DRG were reported to contribute to both the initiation and persistence of neuropathic pain in wild mice, rather than the macrophages at the injury site [ 12 ]. Prior studies show that the number of activated macrophages (Iba1+ cells) in the DRG began increasing 2–4 days after peripheral nerve injury and remained elevated in early phases (2–4 weeks) [ 6 , 30 , 40 , 41 ]. However, macrophage behavior at or after 6 weeks and comparisons between Wistar and nude rats have yet to be reported.…”

Section: Discussionmentioning

confidence: 99%

“…The number of positive cells in the images was blindly counted using Image J software (National Institutes of Health, Bethesda, MD, USA) [ 15 ] and averaged for further analysis. To determine the percentage of labeled neurons in the DRG, the number of positive neurons (three times the background signal) was divided by the total number of neurons [ 6 ].…”

Section: Methodsmentioning

confidence: 99%

“…Autotomy, self-mutilation of a denervated limb [ 5 , 6 , 7 , 8 ], is very common in animals after PNI (e.g., mice, rats, and rabbits), especially in rats after sciatic nerve transection, when the incidence of autotomy reaches as high as 40–80% [ 5 , 7 , 9 ]. This behavior is painful and affects animal behavioral outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury

Zhou

et al. 2021

IJMS

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Autotomy, self-mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to investigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macrophage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macrophages were concentrated around NF200-labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macrophages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury

Zhou

et al. 2021

IJMS

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Isoamericanin A improves lipopolysaccharide‐induced memory impairment in mice through suppression of the nicotinamide adenine dinucleotide phosphateoxidase‐dependent nuclear factor kappa B signaling pathway

Yang

Chen

Che

et al. 2023

Phytotherapy Research

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Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly. Isoamericanin A (ISOA) is a natural lignan possessing great potential for AD treatment. This study investigated the efficacy of ISOA on memory impairments in the mice intrahippocampal injected with lipopolysaccharide (LPS) and the underlying mechanism. Y‐maze and Morris Water Maze data suggested that ISOA (5 and 10 mg/kg) ameliorated short‐ and long‐term memory impairments, and attenuated neuronal loss and lactate dehydrogenase activity. ISOA exerted anti‐inflammatory effect demonstrating by the reduction of ionized calcium‐binding adapter molecule 1 positive cells and suppression of marker protein and pro‐inflammation cytokines expressions induced by LPS. ISOA suppressed the nuclear factor kappa B (NF‐κB) signaling pathway by inhibiting IκBα phosphorylation and NF‐κB p65 phosphorylation and nuclear translocation. ISOA inhibited superoxide and intracellular reactive oxygen species accumulation by reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, demonstrating by suppressing NADP+ and NADPH contents, gp91phox expression, and p47phox expression and membrane translocation. These effects were enhanced in combination with NADPH oxidase inhibitor apocynin. The neuroprotective effect of ISOA was further proved in the in vitro models. Overall, our data revealed a novel pharmacological activity of ISOA: ameliorating memory impairment in AD via inhibiting neuroinflammation.

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Transcriptional profiles of TGF-β superfamily members in the lumbar DRGs and the effects of activins A and C on inflammatory pain in rats

Zhang

Wang

et al. 2023

J Physiol Biochem

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Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel

Cited by 28 publications

References 55 publications

Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury

Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury

Isoamericanin A improves lipopolysaccharide‐induced memory impairment in mice through suppression of the nicotinamide adenine dinucleotide phosphateoxidase‐dependent nuclear factor kappa B signaling pathway

Transcriptional profiles of TGF-β superfamily members in the lumbar DRGs and the effects of activins A and C on inflammatory pain in rats

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