摘要
骨质疏松症(osteoporosis,OP)是中老年人常见的全身代谢性骨病,目前临床医师在OP的治疗中更加关注骨密度的变化,常常忽略OP带来的疼痛,而疼痛是OP最常见、最典型的症状,其长期存在,严重影响患者的生理及心理健康。现阶段,引起OP慢性疼痛的具体机制仍未被阐明,按照病理学特征分类,疼痛可分为伤害感受性疼痛和神经病理性疼痛,其中神经病理性疼痛在OP慢性疼痛中的研究逐渐被重视,可能成为治疗OP慢性疼痛的一把新钥匙。在骨吸收活跃状态,骨与软组织会释放各种刺激因子,ATP是其中一种,同时ATP可充当神经递质,在神经元之间传导冲动,研究证实ATP的释放会导致疼痛的发生,特别是神经病理性疼痛,抑制ATP的释放可以起到抑制疼痛的作用,ATP带有高度负电荷,其释放需要特定蛋白的参与。氯膦酸盐是第一代不含氮双膦酸盐,除抗骨质疏松外,还有良好的镇痛作用。研究发现,氯膦酸盐是一种对囊泡核苷酸转运蛋白选择性强且有效的抑制剂,可以抑制ATP通过囊泡核苷酸转运蛋白进入溶酶体,进而阻断了ATP的释放,达到止痛效果。因此,溶酶体-VNUT-ATP途径在OP慢性疼痛中发挥重要作用,深入研究该途径可以为OP慢性疼痛的治疗提供新的靶点和实验依据,笔者就骨质疏松症慢性疼痛的疼痛类型及ATP释放的其中一条途径(溶酶体-VNUT-ATP)作一简要综述。
Osteoporosis(OP)is a common systemic metabolic bone disease in the middle-aged and elderly.At present,clinicians pay more attention to the changes of bone mineral density in the treatment of OP and often ignore OP-induced pain.Pain is the most common and typical symptom of OP,which exists for a long time and seriously affects the physical and mental health of the patients.At this stage,the specific mechanism of OP chronic pain has not been clarified.According to the classification of pathological characteristics,pain can be divided into nociceptive pain and neuropathic pain.Among them,the research of neuropathic pain in OP chronic pain has been paid more and more attention,which may become a new key to the treatment of OP chronic pain.In the active state of bone resorption,bone and soft tissue may release various stimulating factors.ATP is one of them.At the same time,ATP acts as a neurotransmitter to transmit impulses between neurons.Studies have confirmed that the release of ATP leads to pain,especially neuropathic pain.Inhibiting the release of ATP may inhibit pain.ATP is highly negatively charged,and its release requires the participation of specific proteins.Clodronate is the first generation of nitrogen-free bisphosphonates.In addition to anti-osteoporosis,it also has a good analgesic effect.Studies have found that clodronate is a selective and effective inhibitor of vesicle nucleotide transporter,which prevents ATP from entering the lysosome through vesicle nucleotide transporter,thereby blocking the release of ATP to achieve analgesic effect.Therefore,the lysosomal-VNUT-ATP pathway plays an important role in OP chronic pain.In-depth study of this pathway may provide new targets and experimental basis for the treatment of OP chronic pain.This paper briefly reviews the pain types of OP chronic pain and one of the ways of ATP release:lysosomal-VNUT-ATP.
作者
刘树华
王若琳
陈桐莹
赵宇
王世浩
张桂鑫
黄宏兴
万雷
LIU Shuhua;WANG Ruolin;CHEN Tongying;ZHAO Yu;WANG Shihao;ZHANG Guixin;HUANG Hongxing;WAN Lei(The Third Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou 510405;The Sixth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen 518034;The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510375, China)
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2022年第5期713-717,共5页
Chinese Journal of Osteoporosis
基金
国家自然科学基金(82174395,81973886)
广州中医药大学“双一流”与高水平大学学科协同创新团队项目(2021XK21)。
