Department of Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Orthodontics and Dentofacial Orthodontics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 3-18-15, Kuramotocho, Tokushima, Tokushima, 770-8504, Japan.
Curr Osteoporos Rep. 2018 Dec;16(6):648-656. doi: 10.1007/s11914-018-0489-x.
Sensory nerves (SNs) richly innervate bone and are a component of bone microenvironment. Cancer metastasis in bone, which is under the control of the crosstalk with bone microenvironment, induces bone pain via excitation of SNs innervating bone. However, little is known whether excited SNs in turn affect bone metastasis.
Cancer cells colonizing bone promote neo-neurogenesis of SNs and excite SNs via activation of the acid-sensing nociceptors by creating pathological acidosis in bone, evoking bone pain. Denervation of SNs or inhibition of SN excitation decreases bone pain and cancer progression and increases survival in preclinical models. Importantly, patients with cancers with increased SN innervation complain of cancer pain and show poor outcome. SNs establish the crosstalk with cancer cells to contribute to bone pain and cancer progression in bone. Blockade of SN excitation may have not only analgesic effects on bone pain but also anti-cancer actions on bone metastases.
感觉神经（SNs）丰富地支配骨骼，并构成骨骼微环境的一个组成部分。骨骼中的癌症转移受与骨骼微环境相互作用的控制，通过兴奋支配骨骼的 SNs 来引发骨痛。然而，对于兴奋的 SNs 是否反过来影响骨骼转移，人们知之甚少。
定植于骨骼的癌细胞通过在骨骼中产生病理性酸中毒来促进 SNs 的新生神经支配，并通过激活酸敏伤害感受器来兴奋 SNs，从而引发骨痛。SNs 的去神经支配或抑制 SN 兴奋可减少骨痛和癌症进展，并增加临床前模型中的存活率。重要的是，具有增加的 SN 支配的癌症患者会抱怨癌症疼痛，并表现出不良的预后。SNs 与癌细胞建立了相互作用，有助于骨骼中的骨痛和癌症进展。阻断 SN 兴奋不仅对骨痛具有镇痛作用，而且对骨骼转移也具有抗癌作用。
