IBMS BoneKEy | Perspective
Molecular events of acid-induced bone pain
Toshiyuki Yoneda
Kenji Hata
Masako Nakanishi
Maho Nagae
Tomotaka Nagayama
Hiroki Wakabayashi
Toshihiko Nishisho
Teruhisa Sakurai
Toru Hiraga
DOI:10.1138/20110507
Abstract
Pain is one of the most common and feared complications in patients with any disease. Pain causes discomfort, depression and anxiety and occasionally induces secondary diseases due to its immunosuppressive effects, making quality of life and prognosis worse. Pain is triggered following the recognition of local noxious stimuli by specialized afferent sensory neurons called nociceptors. The nociceptors can sense diverse noxious stimuli including thermal, mechanical and chemical agents that are released from inflammatory cells, immune cells, cancer cells and/or bone-destroying osteoclasts invading disease sites and injured tissues. Protons are one of these noxious stimuli and have long been known as a cause of pain. Sensory neurons innervating peripheral tissues can sense protons via acid-sensing nociceptors such as transient receptor potential channel vanilloid subfamily members. Noxious acid stimulus received by these nociceptors subsequently activates intracellular signaling pathways and transcription factors, leading to the release of neurotransmitters, including calcitonin gene-related peptide, in sensory neuronal cells. This Perspective describes intracellular molecular events propagated in sensory neurons as a consequence of acid activation of nociceptors, with a special emphasis on bone pain. Understanding the molecular events underlying acid-induced bone pain may lead to the design of novel mechanism-based approaches for the management of bone pain associated with inflammation and cancer metastasis.
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