Ion Channels in Cancer-induced Bone Pain: from Molecular Mechanisms to Clinical Applications

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2023 Sep 4

PMID 37664239

Authors

Huan-Jun Lu

Xiao-Bo Wu

Qian-Qi Wei

Affiliations

Soon will be listed here.

Abstract

Cancer-induced bone pain (CIBP) caused by bone metastasis is one of the most prevalent diseases, and current treatments rely primarily on opioids, which have significant side effects. However, recent developments in pharmaceutical science have identified several new mechanisms for CIBP, including the targeted modification of certain ion channels and receptors. Ion channels are transmembrane proteins, which are situated on biological cell membranes, which facilitate passive transport of inorganic ions across membranes. They are involved in various physiological processes, including transmission of pain signals in the nervous system. In recent years, there has been an increasing interest in the role of ion channels in chronic pain, including CIBP. Therefore, in this review, we summarize the current literature on ion channels, related receptors, and drugs and explore the mechanism of CIBP. Targeting ion channels and regulating their activity might be key to treating pain associated with bone cancer and offer new treatment avenues.

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References

Rami H, Thompson M, Stemp G, Fell S, Jerman J, Stevens A . Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development. Bioorg Med Chem Lett. 2006; 16(12):3287-91. DOI: 10.1016/j.bmcl.2006.03.030. View

Montell C . Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci STKE. 2001; 2001(90):re1. DOI: 10.1126/stke.2001.90.re1. View

Moqrich A, Hwang S, Earley T, Petrus M, Murray A, Spencer K . Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science. 2005; 307(5714):1468-72. DOI: 10.1126/science.1108609. View

Jin X, Cheng J, Zhang Q, Ji H, Zhu C, Yang Y . Aconitine - A promising candidate for treating cold and mechanical allodynia in cancer induced bone pain. Biomed Pharmacother. 2023; 161:114284. DOI: 10.1016/j.biopha.2023.114284. View

Menendez L, Juarez L, Garcia E, Garcia-Suarez O, Hidalgo A, Baamonde A . Analgesic effects of capsazepine and resiniferatoxin on bone cancer pain in mice. Neurosci Lett. 2005; 393(1):70-3. DOI: 10.1016/j.neulet.2005.09.046. View

Lee C, Chen C . Roles of ASICs in Nociception and Proprioception. Adv Exp Med Biol. 2018; 1099:37-47. DOI: 10.1007/978-981-13-1756-9_4. View

Gavva N, Treanor J, Garami A, Fang L, Surapaneni S, Akrami A . Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain. 2008; 136(1-2):202-10. DOI: 10.1016/j.pain.2008.01.024. View

Tabarowski Z, Felten S . Noradrenergic and peptidergic innervation of the mouse femur bone marrow. Acta Histochem. 1996; 98(4):453-7. DOI: 10.1016/S0065-1281(96)80013-4. View

Baldo B . Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity, serotonin toxicity. Arch Toxicol. 2021; 95(8):2627-2642. DOI: 10.1007/s00204-021-03068-2. View

10.

Wang J, Zhang R, Dong C, Jiao L, Xu L, Liu J . Transient Receptor Potential Channel and Interleukin-17A Involvement in LTTL Gel Inhibition of Bone Cancer Pain in a Rat Model. Integr Cancer Ther. 2015; 14(4):381-93. DOI: 10.1177/1534735415580677. View

11.

Fayad S, Ourties G, Le Gac B, Jouffre B, Lamoine S, Fruquiere A . Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain. Elife. 2022; 11. PMC: 9714965. DOI: 10.7554/eLife.79018. View

12.

Nilius B, Appendino G, Owsianik G . The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch. 2012; 464(5):425-58. DOI: 10.1007/s00424-012-1158-z. View

13.

Latremoliere A, Woolf C . Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009; 10(9):895-926. PMC: 2750819. DOI: 10.1016/j.jpain.2009.06.012. View

14.

Weber L, Al-Refae K, Wolk G, Bonatz G, Altmuller J, Becker C . Expression and functionality of TRPV1 in breast cancer cells. Breast Cancer (Dove Med Press). 2016; 8:243-252. PMC: 5167528. DOI: 10.2147/BCTT.S121610. View

15.

Harrison J, Rameshwar P, Chang V, Bandari P . Oxygen saturation in the bone marrow of healthy volunteers. Blood. 2002; 99(1):394. DOI: 10.1182/blood.v99.1.394. View

16.

Wang X, Lan H, Shen T, Gu P, Guo F, Lin X . Perineural invasion: a potential reason of hepatocellular carcinoma bone metastasis. Int J Clin Exp Med. 2015; 8(4):5839-46. PMC: 4483997. View

17.

Maes C, Carmeliet G, Schipani E . Hypoxia-driven pathways in bone development, regeneration and disease. Nat Rev Rheumatol. 2012; 8(6):358-66. DOI: 10.1038/nrrheum.2012.36. View

18.

Poco Goncalves J, Veiga D, Araujo A . Chronic pain, functionality and quality of life in cancer survivors. Br J Pain. 2021; 15(4):401-410. PMC: 8611292. DOI: 10.1177/2049463720972730. View

19.

Cheng Y, Jiang B, Chen C . Acid-sensing ion channels: dual function proteins for chemo-sensing and mechano-sensing. J Biomed Sci. 2018; 25(1):46. PMC: 5966886. DOI: 10.1186/s12929-018-0448-y. View

20.

Inoue K, Tsuda M . Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci. 2018; 19(3):138-152. DOI: 10.1038/nrn.2018.2. View