Behavioral Compensations and Neuronal Remodeling in a Rodent Model of Chronic Intervertebral Disc Degeneration

Leimer, Elizabeth M.; Gayoso, Matthew G.; Jing, Liufang; Tang, Simon Y.; Gupta, Munish C.; Setton, Lori A.

doi:10.1038/s41598-019-39657-6

Cited by 30 publications

(39 citation statements)

References 40 publications

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“…Pathological innervation of the disc by pain-sensing nerve fibers is thought to be a key component of discogenic pain [35,36]. In this study, we found that IVDD mice exhibited a significant increase in the number of Cgrp + sensory nerves both in outer AF and ectopic bone formation zone, and WBV treatment further increases the density of Cgrp + sensory nerves in outer AF.…”

Section: Discussionsupporting

confidence: 49%

Whole-body Vibration Attenuates Pyroptosis-Mediated Inflammation but Accelerates Progression of Intervertebral Disc Degeneration

Yao

Sun³

et al. 2020

Preprint

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Background Whole body vibration (WBV) is a non-pharmaceutical therapy that has been widely incorporated into clinical practice for musculoskeletal disorders, including low back pain (LBP). Intervertebral disc (IVD) degeneration (IVDD) is clinically associated with LBP and is known as the main cause for LBP. However, cumulative evidence also suggested WBV might have an adverse impact on IVDs. Moreover, previous studies have been focusing on the effects of WBV on healthy mice, rather than those suffering from IVDD. Thus, uncertainties still exist concerning the effects of WBV on IVDs undergoing IVDD. This study was aiming to evaluate the effects of WBV intervention on the development and progression of IVDD mouse model induced by lumbar spine instability (LSI) surgery. Methods LSI surgery, by resecting the lumbar 3 rd -5 th spinous processes along with the supraspinous and interspinous ligaments, was conducted in 10-week-old male mice which then received WBV treatment (1 h per day, 5 days per week, at 3 Hz with peak acceleration at 0.4 g) or sham treatment. The progression of IVDD was evaluated by MRI, μCT and histological analyses after WBV treatment. The matrix metabolism, distribution of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological analysis or real-time PCR. The apoptosis of IVD cells was detected by TUNEL assay. Results LSI surgery was successful in producing IVDD modeling. WBV caused decreases in IVD height and annulus fibrosus (AF) score, as well as increased numbers of apoptotic cells in IVD tissues. WBV contributed to sensory innervation into AF and upregulation of Adamts5 and MMP3 expression in IVDD mice received LSI surgery. In addition, WBV treatment triggered earlier activation of Wnt/β-catenin signaling in IVDD mice with WBV treatment compared with those without WBV treatment. Unexpectedly, WBV significantly attenuated Caspase-1 and IL-1β expression in AF. Conclusions Collectively, our findings demonstrate that WBV treatment may worsen the development of ongoing IVDD. Decrease of IL-1β expression after WBV intervention may partially account for patient self-reported pain relief after WBV treatment in some previous trials. This study may help us better understand the effects of WBV intervention on patients experiencing LBP resulting from the degeneration of lumbar IVDs.

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Section: Discussionsupporting

confidence: 49%

Whole-body Vibration Attenuates Pyroptosis-Mediated Inflammation but Accelerates Progression of Intervertebral Disc Degeneration

Yao

Sun³

et al. 2020

Preprint

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“…selected activity was assessed by tracking mouse movement within a custom arena (40 cm x 40 cm x 40 cm)[27][28][29] . Movement within a 30 min recording period was analyzed J o u r n a l P r e -p r o o f (EthoVision, Noldus, Wageningen, NLD) to determine the change in distance traveled from data acquired at baseline.In Situ Live-Dead Cellular ImagingTo determine the immediate effects of PHA-408 on chondrocyte cell viability, intact femurs from animals in cohort 2 were harvested 48 h following joint injury.…”

mentioning

confidence: 99%

NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis

Berke

Jain

Yavuz

et al. 2021

Osteoarthritis and Cartilage

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“…Neurons surviving after peripheral nerve injury can exhibit certain ultrastructural changes associated with axon regeneration, such as nuclear and neuronal hypertrophy, due to the elevated metabolic and transcriptional activity (Leimer et al, 2019;Pannese, 1963). Neuronal hypertrophy is observed in DRG neurons upon ileum hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

New approaches to the design of analgesic medicinal substances

Rogachevskii

Plakhova

Penniyaynen

et al. 2022

Can. J. Physiol. Pharmacol.

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A gamma-pyrone derivative, comenic acid, activates the opioid-like receptor-mediated signaling pathway that modulates the NaV1.8 channels in the primary sensory neuron membrane. These channels are responsible for generation of the nociceptive signal; gamma-pyrones can therefore have a great therapeutic potential as analgesics, and this effect deserves a deeper understanding. The novelty of our approach to the design of a medicinal substance is based on a combination of the data obtained on living neurons using very sensitive physiological methods and the results of quantum-chemical calculations. This approach allows to correlate the molecular structure of gamma-pyrones with their ability to evoke a physiological response of the neuron. Comenic acid can bind two calcium cations. One of them is chelated by the carbonyl and the hydroxyl functional groups, while another one forms the salt bond with the carboxylate anion. Calcium-bound gamma-pyrones are fundamentally different in electrostatic properties from the free gamma-pyrone molecules. These two calcium ions are the key elements involved in ligand-receptor binding. It is very likely ion-ionic interactions between these cations and anionic functional groups of the opioid-like receptor that activate the latter. The calculated intercationic distance of 9.5 Å is a structural criterion for effective ligand-receptor binding of calcium-bound gamma-pyrones.

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Behavioral Compensations and Neuronal Remodeling in a Rodent Model of Chronic Intervertebral Disc Degeneration

Cited by 30 publications

References 40 publications

Whole-body Vibration Attenuates Pyroptosis-Mediated Inflammation but Accelerates Progression of Intervertebral Disc Degeneration

Whole-body Vibration Attenuates Pyroptosis-Mediated Inflammation but Accelerates Progression of Intervertebral Disc Degeneration

NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis

New approaches to the design of analgesic medicinal substances

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