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PGE2/EP4 skeleton interoception activity reduces vertebral endplate porosity and spinal pain with low-dose celecoxib
Bone Research ( IF 12.7 ) Pub Date : 2021-08-02 , DOI: 10.1038/s41413-021-00155-z
Peng Xue 1, 2, 3 , Shenyu Wang 1 , Xiao Lyu 1 , Mei Wan 1 , Xialin Li 1 , Lei Ma 4 , Neil C Ford 5 , Yukun Li 2 , Yun Guan 5 , Wenyuan Ding 4 , Xu Cao 1
Affiliation  

Skeletal interoception regulates bone homeostasis through the prostaglandin E2 (PGE2) concentration in bone. Vertebral endplates undergo ossification and become highly porous during intervertebral disc degeneration and aging. We found that the PGE2 concentration was elevated in porous endplates to generate spinal pain. Importantly, treatment with a high-dose cyclooxygenase 2 inhibitor (celecoxib, 80 mg·kg−1 per day) decreased the prostaglandin E2 concentration and attenuated spinal pain in mice with lumbar spine instability. However, this treatment impaired bone formation in porous endplates, and spinal pain recurred after discontinuing the treatment. Interestingly, low-dose celecoxib (20 mg·kg−1 per day, which is equivalent to one-quarter of the clinical maximum dosage) induced a latent inhibition of spinal pain at 3 weeks post-treatment, which persisted even after discontinuing treatment. Furthermore, when the prostaglandin E2 concentration was maintained at the physiological level with low-dose celecoxib, endplate porosity was reduced significantly, which was associated with decreased sensory nerve innervation and spinal pain. These findings suggest that low-dose celecoxib may help to maintain skeletal interoception and decrease vertebral endplate porosity, thereby reducing sensory innervation and spinal pain in mice.



中文翻译:

PGE2/EP4 骨骼内感受活性通过低剂量塞来昔布减少椎骨终板孔隙率和脊柱疼痛

骨骼内感受通过骨中的前列腺素 E2 (PGE2) 浓度调节骨稳态。在椎间盘退变和老化期间,椎骨终板经历骨化并变得高度多孔。我们发现多孔终板中的 PGE2 浓度升高会产生脊柱疼痛。重要的是,用高剂量环氧合酶 2 抑制剂(塞来昔布,80 mg·kg -1 每天)治疗降低了前列腺素 E2 浓度并减轻了腰椎不稳小鼠的脊椎疼痛。然而,这种治疗损害了多孔终板的骨形成,停止治疗后脊椎疼痛复发。有趣的是,低剂量塞来昔布(20 mg·kg -1 每天,相当于临床最大剂量的四分之一)在治疗后 3 周诱导脊髓疼痛的潜伏抑制,即使在停止治疗后仍持续存在。此外,当使用低剂量塞来昔布将前列腺素 E2 浓度维持在生理水平时,终板孔隙率显着降低,这与感觉神经支配和脊髓疼痛减少有关。这些发现表明,低剂量塞来昔布可能有助于维持骨骼内感受并减少椎骨终板孔隙率,从而减少小鼠的感觉神经支配和脊髓疼痛。

更新日期:2021-08-02
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