Interleukin-6 Inhibitor Suppresses Hyperalgesia Without Improvement in Osteoporosis in a Mouse Pain Model of Osteoporosis

Wakabayashi, Hiroki; Kato, Sho; Nagao, Nobuto; Miyamura, Gaku; Naito, Yohei; Sudo, Akihiro

doi:10.1007/s00223-019-00521-4

Cited by 14 publications

(21 citation statements)

References 32 publications

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“…At the end of the 4-week treatment period, isolated tibias were imaged using a μCT scanner (R_mCT; Rigaku Corporation, Tokyo, Japan), as described previously, to determine the three-dimensional bone microstructure. 12,13 Three-dimensional images were reconstructed and analyzed using three-dimensional image analysis software (TRI/3D-BONE, RATOC System Engineering, Tokyo, Japan). Osteoporotic evaluation was performed on the basis of bone volume and tissue volume fraction (BV/VT, %), trabecular number (Tb.N, /mm), trabecular thickness (Tb.Th, μm), and trabecular separation (Tb.Sp, μm).…”

Section: Methodsmentioning

confidence: 99%

“…Isolated hind limb bones and immunostained sections were prepared as described previously. 12,13 Sections were stained with hematoxylin and eosin for histological analysis of the bone structure. To identify osteoclasts in hind limb bone, the tartrate-resistant acid phosphatase (TRAP) method was used.…”

Section: Methodsmentioning

confidence: 99%

“…Experiments were conducted on 8-week-old female ddY mice weighing 34-39 g, as per previous reports. 12,13 The mice were housed in a temperature-controlled room (23 + 1 C) with a 12-h light/12-h dark cycle (lights on from 7:00 to 19:00) and with free access to food and water.…”

Section: Animalsmentioning

confidence: 99%

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Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice

Kato

Wakabayashi

Nakagawa

et al. 2019

J Orthop Surg (Hong Kong)

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Purpose: The aim of this study was to examine the inhibitory effect of teriparatide (TPTD) on pain and on bone loss in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated through an examination of pain-related behavior as well as immunohistochemical examinations. Methods: Eight-week-old female ddY mice were OVX and assigned to one of three groups: (1) OVX mice treated with vehicle (OVX), (2) OVX mice treated with teriparatide (OVX-TPTD), or (3) SHAM-operated mice treated with vehicle (SHAM). Starting immediately after surgery, vehicle or TPTD was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was tested using von Frey filaments. The proximal tibial metaphyses were analyzed three-dimensionally by microcomputed tomography (μCT). Calcitonin gene-related peptide (CGRP) and transient receptor potential channel vanilloid 1 (TRPV1) expressions in L3–5 dorsal root ganglion (DRG) neurons were examined using immunohistochemistry. Results: Ovariectomy induced bone loss and mechanical hyperalgesia in the hind limbs with upregulation of CGRP and TRPV1 expressions in DRG neurons innervating the hind limbs. Bone loss was prevented more effectively in the OVX-TPTD mice than in the OVX mice. Furthermore, mechanical hyperalgesia and upregulation of CGRP and TRPV1 expressions were significantly lower in the OVX-TPTD mice than in the OVX mice. Conclusion: TPTD treatment prevented ovariectomy-induced bone loss and ovariectomy-induced mechanical hyperalgesia in hind limbs, and it suppressed CGRP and TRPV1 expressions in DRG neurons. These results suggest that TPTD is useful for the treatment of osteoporotic pain in postmenopausal women.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice

Kato

Wakabayashi

Nakagawa

et al. 2019

J Orthop Surg (Hong Kong)

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“…Так, на биологических моделях было показано, что введение ИЛ6 внутривенно или непосредственно в ликвор приводит к появлению гипералгезии и аллодинии, т. е. непосредственно вызывает ЦС. При этом параллельное введение gp130 -растворимого рецептора ИЛ6, связывающего этот цитокин, полностью устраняет действие последнего на ноцицептивную систему [36][37][38]. Более того, нанесение раствора ФНОα и ИЛ1β на пластинку нейронов из изолированного участка спинного мозга значительно усиливало электрическую активность нервной ткани -частоту и амплитуду спонтанных возбуждающих постсинаптических токов (sEPSC).…”

Section: механизм развития боли при иммуновоспалительных ревматическиunclassified

Chronic pain and central sensitization in immuno-inflammatory rheumatic diseases: pathogenesis, clinical manifestations, the possibility of using targeted disease modifying antirheumatic drugs

Каратеев¹,

Насонов

2019

Naučno-praktičeskaâ revmatologiâ

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Chronic pain is one of the main manifestations of immuno-inflammatory rheumatic diseases (IIRD), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which determines the severity of suffering, reduced quality of life and disability of patients. Unfortunately, the use of synthetic and biological disease modifying antirheumatic drugs, as well as non-steroidal anti-inflammatory drugs does not always provide sufficient control of pain in IIRD, even when it is possible to achieve a significant reduction in inflammatory activity. The reason for this is the complex mechanism of chronic pain. It includes not onlystimulation of pain receptors caused by damage of the elements of the musculoskeletal system, but also a change in the perception of pain associated with the phenomenon of central sensitization (CS). CS is characterized by a significant and persistent increase in the sensitivity of nociceptive neurons to pain and nonpain stimuli. One of the main theories of the CS development consider this phenomenon as an inflammatory reaction of the neuronenvironmentthe activation of astrocytes and microglial cells, local hyperproduction of cytokines, inflammatory mediators and neurotrophic factors. Factors contributing to the development of CS in IIRD are obesity, depression and anxiety, damage of the somatosensory system, insufficient relief of pain in the onset of the disease. Clinical manifestations of CS in IIRD is hyperalgesia, allodinia, «expanded pain» and secondary fibromyalgia. An important role in the development of chronic pain and CS plays the intracellular inflammatory pathway JAK-STAT. Therefore, JAK inhibitors, such as tofacitinib, used in RA and PsA, can also be considered as an effective means of controlling chronic pain in these diseases.

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“…The term osteoimmunology was adopted by arron and choi (9). Subsequently, it was demonstrated that interleukin (il)-1β (10), il-6 (11)(12)(13)(14)(15), il-10 (16,17) and il-13 (18) are closely linked to osteoporosis. other biomarkers were also indicated to be associated with BMd.…”

Section: Introductionmentioning

confidence: 99%

Cytokines CCL2 and CXCL1 may be potential novel predictors of early bone loss

Wang

Zhao

et al. 2020

Mol Med Rep

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osteoporosis is a common disorder characterized by decreased bone mineral density (BMd) and increased fracture risk. The current techniques detect real-time BMd precisely but do not provide adequate information to predict early bone loss. if bone loss could be diagnosed and predicted early, severe osteoporosis and unexpected fractures could be prevented, allowing for an improved quality of life for individuals. in the present study, an ovariectomized rat model of bone loss was established and the serum levels of 78 potential cytokines were determined using a protein array. The BMd of ovariectomized rats was dynamically measured by micro-cT and the early stage of bone loss was defined at the fourth week after surgery. The expression of several serum protein cytokines was indicated to be altered in the ovariectomized rats during an 8-week time-course of bone loss. linear regression analysis revealed that the serum levels of cc motif chemokine ligand 2 (ccl2, also known as monocyte chemoattractant protein 1) and c-X-c motif chemokine ligand 1 (CXCL1) were significantly associated with a reduction in BMD. The significance of these two factors in indicating bone mass reduction was further verified by analyzing serum samples from 24 patients with BMd using eliSa and performing a linear regression analysis. The serum levels of ccl2 and cXcl1 were inversely correlated with the bone mass. Therefore, the cytokines ccl2 and cXcl1 may be potential novel predictors of early bone loss and may be clinically relevant for the early diagnosis and prevention of osteoporosis.

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Interleukin-6 Inhibitor Suppresses Hyperalgesia Without Improvement in Osteoporosis in a Mouse Pain Model of Osteoporosis

Cited by 14 publications

References 32 publications

Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice

Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice

Chronic pain and central sensitization in immuno-inflammatory rheumatic diseases: pathogenesis, clinical manifestations, the possibility of using targeted disease modifying antirheumatic drugs

Cytokines CCL2 and CXCL1 may be potential novel predictors of early bone loss

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