Alendronate inhibits hyperalgesia and suppresses neuropeptide markers of pain in a mouse model of osteoporosis

Naito, Yohei; Wakabayashi, Hiroki; Kato, Sho; Nakagawa, T; Iino, Takahiro; Sudo, Akihiro

doi:10.1016/j.jos.2017.02.001

Cited by 19 publications

(17 citation statements)

References 21 publications

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“…Mice are commonly used as an animal model for osteoporosis and intervertebral disc degeneration [ 31 – 33 ]. Many studies have demonstrated that the ovariectomized mouse is a good model for postmenopausal osteoporosis [ 34 ]. Thus, the purpose of this study was to determine the roles of postmenopausal osteoporosis in IVDD and to further clarify its underlying mechanism by assessing the detailed pathological changes in L4–L5 spine motion segments including vertebrae, the endplate, and the intervertebral disc in ovariectomized mice.…”

Section: Introductionmentioning

confidence: 99%

Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Xiao

et al. 2018

Arthritis Res Ther

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BackgroundStudies on the relationship between osteoporosis and intervertebral disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is affected by vertebral osteoporosis in ovariectomized mice and investigated the underlying pathogenesis of IVDD related to osteoporosis.MethodsThirty healthy female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and microstructure in the lumbar vertebra and endplate as well as the volume of the L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The occurrence and characteristic alterations of IVDD were identified via histopathological staining. The osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF) expression in the intervertebral disc were detected by immunohistochemical analysis.ResultsOVX significantly increased the body weight and decreased the uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and osteochondral remodeling of the endplate were accompanied by an increase in the endplate porosity and a decrease in the disc volume in the OVX group. Likewise, histological evaluation revealed that IVDD occurred at 12 weeks after ovariectomy, with features of endochondral ossification of the endplate, loose and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining showed that numerous active osteoclasts appeared in the subchondral bone and cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in control mice. Immunohistochemical analysis demonstrated that the expression of osterix was significantly increased, notably in the endplate of OVX mice. In addition, Col II was decreased in the ossification endplate and the degenerative annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice.ConclusionsOVX induced vertebral osteoporosis and osteochondral remodeling of the cartilaginous endplate contributing to the angiogenesis and an increase in porosity of the bone-cartilage surface, and also affected the matrix metabolism which consequently had detrimental effects on the intervertebral disc. Our study suggests that preserving the structural integrity and the function of the adjacent structures, including the vertebrae and endplates, may protect the disc against degeneration.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1701-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Xiao

et al. 2018

Arthritis Res Ther

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“…TRPV1 knockout reduces the number of osteoclasts, impairs the osteoclast formation and resorption activity, decreases the oscillation frequency and peak concentration of cytoplasmic calcium in osteoclast precursors . Consistently, ovariectomy of mice produces osteoporosis and mechanical hyperalgesia, and up‐regulates the expression of TRPV1 channel and calcitonin gene‐related peptide (CGRP) in dorsal root ganglion DRG) neurons . It is found that the TRPV1‐positive neurons are increased in DRG innervating osteoporotic femur of mice while the DRG neurons are sensory neurons playing critical role in pain transmission.…”

Section: Mechanism Of Cb In Osteoporotic Painmentioning

confidence: 92%

“…[10] Consistently, ovariectomy of mice produces osteoporosis and mechanical hyperalgesia, and up-regulates the expression of TRPV1 channel and calcitonin gene-related peptide (CGRP) in dorsal root ganglion DRG) neurons. [30] It is found that the TRPV1-positive neurons are increased in DRG innervating osteoporotic femur of mice [9] while the DRG neurons are sensory neurons playing critical role in pain transmission. Inhibition of TRPV1 channel can attenuate pain behaviours in mice with osteoporosis induced by OVX.…”

Section: Interaction Of Cb Receptors With Trpv1 Channelmentioning

confidence: 99%

“…[40] Huo W (2018) Microglia is involved in bone cancer pain [14,31] Kanaya K (2016) TRPV1 channel is involved in osteoporotic pain via osteoclast activity. [16,28,38] Lozano-Ondoua AN (2010, 2013), Lu C (2017) Activation of CB2 receptor attenuates breast cancerinduced bone pain and bone loss [37] Miost J (2018) Activation of CB1and blockade of TRPV1 receptor attenuate osteoarthritis [30] Naito Y (2017) Osteoporotic pain involves TRPV1 activation and CGRP expression to affect bone resorption [11] Reni C (2016) TRPV1 channel is involved in diabetes-induced osteoporotic pathology [17] Samir SM (2014) CB1 receptor is involved in osteoporosis [9] Yoshino K (2014) Osteoporosis increases TRPV1 activities in DRG neurons innervating femur…”

Section: Reference Numbermentioning

confidence: 99%

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Cannabinoid receptors in osteoporosis and osteoporotic pain: a narrative update of review

Wang

2019

Journal of Pharmacy and Pharmacology

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Objective Osteoporosis is a skeletal disease with decreased bone mass and alteration in microarchitecture of bone tissue, and these changes put patients in risk of bone fracture. As a common symptom of osteoporosis and complication of osteoporotic fracture, chronic pain is a headache for clinicians. Nonsteroidal anti‐inflammatory drugs (NSAIDs), selective COX‐2 inhibitors and opioid drugs can temporarily reduce osteoporotic pain but have relevant side effects, such as addiction, tolerability and safety. The review summarized the recent advancements in the study of CB receptors in osteoporosis and osteoporotic pain and related mechanisms. Key findings Recent studies indicated the two nociceptive receptors, cannabinoid receptor (CB) and transient receptor potential vanilloid type 1 (TRPV1) channel, are co‐expressed in bone cells and play important role in the metabolism of bone cells, suggesting that dualtargeting these 2 receptors/channel may provide a novel approach for osteoporotic pain. In addition, both CB receptor and TRPV1 channel are found to be expressed in the glial cells which play vital role in mediating inflammation, chronic pain and metabolism of bone cells, suggesting a role of glial cells inosteoporotic pain. Summary Multiple‐targeting against glial cells, CB receptors and TRPV1 channel may be one effective therapeutic strategy for osteoporotic pain in the future, following the elucidation of the complicated mechanism.

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“…In the present study, to evaluate the effect of minodronate on chronic pain, we used an ovariectomized and chronic constriction injury (CCI) model of the sciatic nerve as the chronic pain model (2). Several previous studies have demonstrated that ovariectomy causes an osteoporosis and hypersensitivity to mechanical or thermal pain (1,19). CCI model rats have shown hypersensitivity to nociceptive pain, decrease in bone mineral density, and muscle atrophy (15,28).…”

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confidence: 99%

<b>Analgesic effects of minodronate in a rat chronic pain </b><b>model </b>

et al. 2018

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We evaluated the analgesic effects of minodronate, alendronate and pregabalin on mechanical and thermal allodynia, as well as changes in bone mineral density and skeletal muscle volume caused by chronic constriction injury (CCI) in an ovariectomized rat. Ovariectomy was performed on four-week-old female Wistar rats. Thereafter, at 8-weeks of age, the left sciatic nerve was ligated to create the chronic pain model (CCI limb), and sham surgery was performed on the right hindlimb. In all rats, either minodronate (0.15 mg/kg/week), alendronate (0.15 mg/kg/week), pregabalin (10 mg/kg/week), or their vehicle was administered for 2 weeks starting on the 0th day of CCI. Behavioral evaluations, with von Frey testing and the hot plate test, were performed on days 0, 7 and 14. After 2 weeks, bilateral femurs and tibialis anterior muscles were harvested for bone mineral density and cross sectional area measurements, respectively. Two weeks treatment with minodronate significantly improved mechanical and thermal allodynia evaluated by the von Frey and hot plate tests in the CCI limb (P < 0.05). Minodronate and alendronate treatment for 2 weeks significantly increased total femoral bone mineral density in the CCI limb compared with pregabalin or vehicle treatment (P < 0.01). Cross sectional area of the CCI limb in the minodronate group was significantly larger than that of the alendronate group (P < 0.05) and pregabalin group (P < 0.05). Two-week treatment with minodronate, but not alendronate or pregabalin, improved mechanical and thermal allodynia caused by CCI in ovariectomized rats.

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Alendronate inhibits hyperalgesia and suppresses neuropeptide markers of pain in a mouse model of osteoporosis

Cited by 19 publications

References 21 publications

Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Cannabinoid receptors in osteoporosis and osteoporotic pain: a narrative update of review

<b>Analgesic effects of minodronate in a rat chronic pain </b><b>model </b>

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