Upregulation of Spinal Voltage-Dependent Anion Channel 1 Contributes to Bone Cancer Pain Hypersensitivity in Rats

Kong, Xiang‐Peng; Wei, Jinrong; Wang, Diyu; Zhu, Xiao; Zhou, Youlang; Wang, Shusheng; Xu, Guang–Yin; Jiang, Guoqin

doi:10.1007/s12264-017-0195-1

Cited by 15 publications

(9 citation statements)

References 36 publications

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“…In agreement with the lack of microglial reaction, minocycline did not cause any alteration of the pain-like phenotype of cancer-bearing rats. While single intrathecal administration of minocycline has previously been reported as anti-nociceptive in this model [ 30 , 46 , 57 ], repeated dosing may be necessary to attenuate CIBP. There is only little evidence of the involvement of microglia in human pain states and, so far, most clinical trials of microglia modulatory agents have not had robust or consistent results [ 58 , 59 , 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Rat Cancer-Induced Bone Pain is Independent of Spinal Microglia Activity

Diaz‐delCastillo

Hansen

Appel

et al. 2020

Cancers

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The dissemination of cancer to bone can cause significant cancer-induced bone pain (CIBP), severely impairing the patient’s quality of life. Several rodent models have been developed to explore the nociceptive mechanisms of CIBP, including intratibial inoculation of breast carcinoma cells in syngeneic Sprague Dawley rats. Using this model, we investigated whether resident spinal microglial cells are involved in the transmission and modulation of CIBP, a long-debated disease feature. Immunohistochemical staining of ionizing calcium-binding adaptor molecule 1 (Iba-1) and phosphorylated p38-mitogen-activated protein kinase (P-p38 MAPK) showed no spinal microglial reaction in cancer-bearing rats, independently of disease stage, sex, or carcinoma cell line. As a positive control, significant upregulation of both Iba-1 and P-p38 was observed in a rat model of neuropathic pain. Additionally, intrathecal administration of the microglial inhibitor minocycline did not ameliorate pain-like behaviors in cancer-bearing rats, in contrast to spinal morphine administration. Our results indicate that microglial reaction is not a main player in CIBP, adding to the debate that even within the same models of CIBP, significant variations are seen in disease features considered potential drug targets. We suggest that this heterogeneity may reflect the clinical landscape, underscoring the need for understanding the translational value of CIBP models.

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Section: Discussionmentioning

confidence: 99%

Modulation of Rat Cancer-Induced Bone Pain is Independent of Spinal Microglia Activity

Diaz‐delCastillo

Hansen

Appel

et al. 2020

Cancers

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“…Gestational psychosocial factors lead to increased inflammation, which influences the development of adult gastrointestinal disease. Maternal psychosocial factors contribute to higher circulating levels of inflammation markers, such as H 2 S 33 and the proinflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and TRL4, 34 which are involved in many pain condition, such as bone cancer pain 35 , 36 and neuropathic pain. 37 As reviewed by Entringer et al., H 2 S had a direct programming effects of maternal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Prenatal maternal stress induces visceral hypersensitivity of adult rat offspring through activation of cystathionine-β-synthase signaling in primary sensory neurons

et al. 2018

Self Cite

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Irritable bowel syndrome is a disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that stressors presented during gestational periods could have long-term effects on the offspring’s tissue structure and function, which may predispose to gastrointestinal diseases. The aim of the present study is to determine whether prenatal maternal stressis a adverse factor affecting gastrointestinal sensitivity and to investigate possible mechanisms underlying prenatal maternal stress-induced visceral hypersensitivity in adult offspring. Prenatal maternal stress was induced in pregnant Sprague–Dawley rats by exposure to heterotypic intermitent stress from gestational day 7 to delivery. Prenatal maternal stress significantly increased visceromotor response to colorectal distention in adult offspring from the age of 6 weeks to 10 weeks. Prenatal maternal stress also enhanced neuronal excitability including depolarization of resting membrane potentials, reduction in rheobase, and an increase in the number of action potentials evoked by 2× and 3× rheobase current stimultion of colon-specific dorsal root ganglion neurons. Prenatal maternal stress remarkably enhanced expression of cystathionine-β-synthase and Nav1.7 in T13-L2 thoracolumbar dorsal root ganglions both at protein and mRNA levels. Intraperitoneal injection of aminooxyacetic acid, an inhibitor of cystathionine-β-synthase, attenuated prenatal maternal stress-induced visceral hypersensitivity in a dose-dependent manner. A consecutive seven-day administration of aminooxyacetic acid reversed the hyperexcitability of colon-specific dorsal root ganglion neurons and markedly reduced Nav1.7 expression. These results indicate that the presence of multiple psychophysical stressors during pregnancy is associated with visceral hypersensitivity in offspring, which is likely mediated by an upregualtion of cystathionine-β-synthase and Nav1.7 expression. Prenatal maternal stress might be a significant contributor to irritable bowel syndrome, and cystathionine-β-synthase might be a potential target for treatment for chronic visceral hypersensitivity in patients with irritable bowel syndrome.

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“…Central sensitization in the spinal cord dorsal horn is closely involved in pain process in lumbar radiculopathy 5,6. Recent researches have been concentrated in the molecular targets in pain-signaling systems, such as G-protein-coupled receptors, ion channels in the glial, and neurons localized within the nociceptive pathways 7. However, the molecular mechanism underlying radicular pain is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

<p>Characterization of novel lnc RNAs in the spinal cord of rats with lumbar disc herniation</p>

Wang

Liu

et al. 2019

JPR

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BackgroundRadicular pain, caused by a lesion or autologous nucleus pulposus (NP) implantation, is associated with alteration in gene expression of the pain-signaling pathways. lncRNAs have been shown to play critical roles in neuropathic pain. However, the mechanistic function of lncRNAs in lumbar disc herniation (LDH) remains largely unknown. Identifying different lncRNA expression under sham and NP-implantation conditions in the spinal cord is important for understanding the molecular mechanisms of radicular pain.MethodsLDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. The mRNA and lncRNA microarray analyses demonstrated that the expression profiles of lncRNAs and mRNAs between the LDH and sham groups were markedly altered at 7 days post operation. The expression patterns of several mRNAs and lncRNAs were further proved by qPCR.ResultsLDH produced persistent mechanical and thermal hyperalgesia. A total of 19 lncRNAs was differentially expressed (>1.5-folds), of which 13 was upregulated and 6 was downregulated. In addition, a total of 103 mRNAs was markedly altered (>1.5-folds), of which 40 was upregulated and 63 downregulated. Biological analyses of these mRNAs further demonstrated that the most significantly upregulated genes in LDH included chemotaxis, immune response, and positive regulation of inflammatory responses, which might be important mechanisms underlying radicular neuropathic pain. These 19 differentially expressed lncRNAs have overlapping mRNAs in the genome, which are related to glutamatergic synapse, cytokine-cytokine receptor interaction, and the oxytocin-signalling pathway.ConclusionOur findings revealed the alteration of expression patterns of mRNAs and lncRNAs in the spinal cord of rats in a radicular pain model of LDH. These mRNAs and lncRNAs might be potential therapeutic targets for the treatment of radicular pain.

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Upregulation of Spinal Voltage-Dependent Anion Channel 1 Contributes to Bone Cancer Pain Hypersensitivity in Rats

Cited by 15 publications

References 36 publications

Modulation of Rat Cancer-Induced Bone Pain is Independent of Spinal Microglia Activity

Modulation of Rat Cancer-Induced Bone Pain is Independent of Spinal Microglia Activity

Prenatal maternal stress induces visceral hypersensitivity of adult rat offspring through activation of cystathionine-β-synthase signaling in primary sensory neurons

<p>Characterization of novel lnc RNAs in the spinal cord of rats with lumbar disc herniation</p>

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