Bupivacaine decreases cell viability and matrix protein synthesis in an intervertebral disc organ model system

Wang, Dong; Vo, Nam; Sowa, Gwendolyn; Hartman, Robert A.; Ngo, Kevin; Choe, So Ra; Witt, William T.; Dong, Qing; Lee, Joon Y.; Niedernhofer, Laura J.; Kang, James D.

doi:10.1016/j.spinee.2010.11.017

Cited by 49 publications

(33 citation statements)

References 30 publications

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“…Both richlocaine and lidocaine belong to the "amide" class of local anesthetics and most of the studies on osteoblasts with local anesthetics were performed with "ester" class of drugs (Cocaine, procaine, and tetracaine). All these ester class drugs were shown to be toxic to osteoblasts even at low range of concentrations [15, 17,23]. Amide drugs might interact differentially with osteoblasts at low concentration by activating signaling pathways (as shown by induction of osteocalcin) while ester drugs might trigger the apoptotic pathways.…”

Section: Discussionmentioning

confidence: 99%

Effect of lidocaine on bone matrix formation by osteoblasts

Pentyala

Hughes²,

Mysore³

et al. 2012

J Anesthesiol Clin Sci

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Local anesthetics are widely used as an intraosseous injection particularly in the field of dentistry. Occasionally, large doses of anesthetics are injected to elicit the desired effect during many surgical procedures. In this study we examined the effect of a local anesthetic, lidocaine, on osteoblasts as there are only a few reports on the effect of local anesthetics directly on bone cells. Our results showed that physiological as well as supra physiological concentrations of lidocaine cause cell death. At low concentrations, lidocaine was found to enhance both proliferation of osteoblasts and bone matrix production. In addition, low concentration of lidocaine increased the expression of osteocalcin, a key regulator in the signaling pathway of bone matrix production. Our results show that lidocaine has a biphasic effect on osteoblasts and low concentrations of this anesthetic may assist in bone matrix production. This preliminary study can lead to the therapeutic usage of intraosseous lidocaine as a bone strengthening agent.

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Section: Discussionmentioning

confidence: 99%

Effect of lidocaine on bone matrix formation by osteoblasts

Pentyala

Hughes²,

Mysore³

et al. 2012

J Anesthesiol Clin Sci

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“…Cells were radiolabeled for two days and extracted by addition of homogenization buffer containing 200 mM sodium chloride, 50 mM sodium acetate, 0.1% Triton X-100 ( Sigma-Aldrich X-100), 10 mM EDTA, 50 μM DTT ( Sigma-Aldrich D9779), and 1x Protease Inhibitor ( Sigma-Aldrich P8340) and shaking at 4°C for 1 hr in a separate 1.5 mL microcentrifuge tube. Proteoglycans in cell lysate were extracted with shaking in a guanidine hydrochloride solution (8 M guanidine hydrochloride ( Sigma-Aldrich G3272) containing 50 mM sodium acetate, 10 mM EDTA, and 1x protease inhibitor at 4°C for 4 hours 22 . Extracted samples were mixed with alcian blue solution containing 0.02% alcian blue ( Sigma-Aldrich A9186), 50 mM sodium acetate, and 85 mM magnesium chloride for an hour at room temperature then loaded onto nitrocellulose membranes ( Millipore HAWP 025 00).…”

Section: Methodsmentioning

confidence: 99%

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype

Ngo

Patil

McGowan

et al. 2017

Mechanisms of Ageing and Development

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Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1−/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss.

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“…(11, 12) Discography, however, may cause further IVD degeneration,(13) due to needle puncture damage and the toxicity of injected anesthetics and contrast media. (14–16) Based on these observations, only patients with severe axial back pain that is suspected to be due to degenerative disc disease are clinical candidates for discography. Patients with severe back pain confirmed to be related to IVD degeneration should undergo cell therapy.…”

Section: Patient Selectionmentioning

confidence: 99%