Advertisement

Current Molecular Biology Reports

, Volume 4, Issue 2, pp 59–68 | Cite as

Bone Pain Associated with Acidic Cancer Microenvironment

  • Toshiyuki Yoneda
  • Masahiro Hiasa
  • Tatsuo Okui
Molecular Biology of Bone Metastasis (H Taipaleenmäki, Section Editor)
  • 29 Downloads
Part of the following topical collections:
  1. Topical Collection on Molecular Biology of Bone Metastasis

Abstract

Purpose of Review

Majority of patients with solid and hematologic cancers associated with osteolytic bone disease suffer from severe uncontrollable bone pain. Treatment of bone pain is an important goal in the management of these cancer patients. However, our understanding of the mechanism underlying cancer-associated bone pain (CABP) is limited and current treatments for CABP are ineffective and unsatisfactory. In this review, the pathophysiology of CABP will be discussed with a special focus on cancer-created acidic bone microenvironment as a potential therapeutic target.

Recent Findings

Recent accumulating findings that sensory nerves (SNs) densely innervate bone suggest that CABP can be induced as a consequence of SN activation by the pathologic changes in bone microenvironment. Cancer cells proliferating in bone secrete protons and lactate resulting from the Warburg effect, creating acidic bone microenvironment. In parallel, cancer in bone increases and activates osteoclasts, which release protons to degrade bone minerals, also making bone microenvironment acidic. The acidic bone microenvironment sensitizes and excites bone-innervating SNs to evoke CABP via upregulation and activation of the acid-sensing nociceptors such as ASIC3 and TRPV1 expressed on SNs. Blockade of the creation of the acidic bone microenvironment and/or interruption of the activation of these nociceptors decrease SN stimulation and CABP.

Summary

Determination of the mechanism by which the acidic cancer microenvironment is generated and by which SN is excited and sensitized via activation of the acid-sensing nociceptors would promote to design mechanism-based novel and effective therapeutic interventions for the management of CABP.

Keywords

Osteoclastic bone resorption Protons Sensory nerves Nociceptors ASIC3 TRPV1 

Notes

Funding Information

This study is supported by the Project Development Team within the ICTSI NIH/NCRR (#TR000006) and start-up fund of Indiana University School of Medicine.

Compliance with Ethical Standards

Conflict of Interest

Toshiyuki Yoneda, Masahiro Hiasa, and Tatsuo Okui declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12(20 Pt 2):6243s–9s.  https://doi.org/10.1158/1078-0432.ccr-06-0931.CrossRefPubMedGoogle Scholar
  2. 2.
    Rizzoli R, Body JJ, Brandi ML, Cannata-Andia J, Chappard D, El Maghraoui A, et al. Cancer-associated bone disease. Osteoporos Int. 2013;24(12):2929–53.  https://doi.org/10.1007/s00198-013-2530-3.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Burrows M, Dibble SL, Miaskowski C. Differences in outcomes among patients experiencing different types of cancer-related pain. Oncol Nurs Forum. 1998;25(4):735–41.PubMedGoogle Scholar
  4. 4.
    Poulos AR, Gertz MA, Pankratz VS, Post-White J. Pain, mood disturbance, and quality of life in patients with multiple myeloma. Oncol Nurs Forum. 2001;28(7):1163–71.PubMedGoogle Scholar
  5. 5.
    •• Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain. 1997;69(1–2):1–18. This paper is one of the earliest articles that introduced the clinical and basic features of CABP CrossRefPubMedGoogle Scholar
  6. 6.
    Patrick DL, Ferketich SL, Frame PS, Harris JJ, Hendricks CB, Levin B, et al. National Institutes of Health State-of-the-Science Conference statement: symptom management in cancer: pain, depression, and fatigue, July 15-17, 2002. J Natl Cancer Inst. 2003;95(15):1110–7.CrossRefPubMedGoogle Scholar
  7. 7.
    •• Mantyh PW. Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci. 2006;7(10):797–809.  https://doi.org/10.1038/nrn1914. This paper dissected and characterized CABP based on preclinical studies using animal models of bone cancer CrossRefPubMedGoogle Scholar
  8. 8.
    Falk S, Dickenson AH. Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol. 2014;32(16):1647–54.  https://doi.org/10.1200/jco.2013.51.7219.CrossRefPubMedGoogle Scholar
  9. 9.
    Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84.  https://doi.org/10.1016/j.cell.2009.09.028.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, et al. Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur. Neuroscience. 2002;113(1):155–66.CrossRefPubMedGoogle Scholar
  11. 11.
    •• Hiasa M, Okui T, Allette YM, Ripsch MS, Sun-Wada GH, Wakabayashi H, et al. Bone pain induced by multiple myeloma is reduced by targeting V-ATPase and ASIC3. Cancer Res. 2017;77(6):1283–95.  https://doi.org/10.1158/0008-5472.can-15-3545. This study shows the importance of the creation of acidic cancer environment and the acid-sensing nociceptor ASIC3 in CABP associated with multiple myeloma CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    • Wakabayashi H, Wakisaka S, Hiraga T, Hata K, Nishimura R, Tominaga M, Yoneda T Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice. J Bone Miner Metab 2017.  https://doi.org/10.1007/s00774-017-0842-7. This work demonstrates critical role of the acid-sensing nociceptor TRPV1 in CABP associated lung cancer using TRPV1 −/− mice.
  13. 13.
    Benemei S, Nicoletti P, Capone JG, Geppetti P. CGRP receptors in the control of pain and inflammation. Curr Opin Pharmacol. 2009;9(1):9–14.  https://doi.org/10.1016/j.coph.2008.12.007.CrossRefPubMedGoogle Scholar
  14. 14.
    Salmon AM, Damaj MI, Marubio LM, Epping-Jordan MP, Merlo-Pich E, Changeux JP. Altered neuroadaptation in opiate dependence and neurogenic inflammatory nociception in alpha CGRP-deficient mice. Nat Neurosci. 2001;4(4):357–8.  https://doi.org/10.1038/86001.CrossRefPubMedGoogle Scholar
  15. 15.
    Mantyh WG, Jimenez-Andrade JM, Stake JI, Bloom AP, Kaczmarska MJ, Taylor RN, et al. Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain. Neuroscience. 2010;171(2):588–98.  https://doi.org/10.1016/j.neuroscience.2010.08.056.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Jimenez-Andrade JM, Bloom AP, Stake JI, Mantyh WG, Taylor RN, Freeman KT, et al. Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain. J Neurosci. 2010;30(44):14649–56.  https://doi.org/10.1523/jneurosci.3300-10.2010.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Johnson RW, Suva LJ. Hallmarks of bone metastasis. Calcif Tissue Int. 2017;102:141–51.  https://doi.org/10.1007/s00223-017-0362-4.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Nagae M, Hiraga T, Yoneda T. Acidic microenvironment created by osteoclasts causes bone pain associated with tumor colonization. J Bone Miner Metab. 2007;25(2):99–104.  https://doi.org/10.1007/s00774-006-0734-8.CrossRefPubMedGoogle Scholar
  19. 19.
    Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001;413(6852):203–10.  https://doi.org/10.1038/35093019.CrossRefPubMedGoogle Scholar
  20. 20.
    Mantyh PW. The neurobiology of skeletal pain. Eur J Neurosci. 2014;39(3):508–19.  https://doi.org/10.1111/ejn.12462.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Krames ES. The dorsal root ganglion in chronic pain and as a target for neuromodulation: a review. Neuromodulation. 2015;18(1):24–32; discussion 32.  https://doi.org/10.1111/ner.12247.CrossRefPubMedGoogle Scholar
  22. 22.
    Cooper RR. Nerves in cortical bone. Science. 1968;160(3825):327–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Serre CM, Farlay D, Delmas PD, Chenu C. Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers. Bone. 1999;25(6):623–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Irie K, Hara-Irie F, Ozawa H, Yajima T. Calcitonin gene-related peptide (CGRP)-containing nerve fibers in bone tissue and their involvement in bone remodeling. Microsc Res Tech. 2002;58(2):85–90.  https://doi.org/10.1002/jemt.10122.CrossRefPubMedGoogle Scholar
  25. 25.
    Fukuda T, Takeda S, Xu R, Ochi H, Sunamura S, Sato T, et al. Sema3A regulates bone-mass accrual through sensory innervations. Nature. 2013;497(7450):490–3.  https://doi.org/10.1038/nature12115.CrossRefPubMedGoogle Scholar
  26. 26.
    Paolucci T, Saraceni VM, Piccinini G. Management of chronic pain in osteoporosis: challenges and solutions. J Pain Res. 2016;9:177–86.  https://doi.org/10.2147/jpr.s83574.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Muralidharan A, Smith MT. Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments. Inflammopharmacology. 2013;21(5):339–63.  https://doi.org/10.1007/s10787-013-0183-7.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lozano-Ondoua AN, Symons-Liguori AM, Vanderah TW. Cancer-induced bone pain: mechanisms and models. Neurosci Lett. 2013;557(Pt A):52–9.  https://doi.org/10.1016/j.neulet.2013.08.003.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yoneda T, Hiasa M, Nagata Y, Okui T, White FA. Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain. Biochim Biophys Acta. 2015;1848(10 Pt B):2677–84.  https://doi.org/10.1016/j.bbamem.2015.02.004.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Maes C, Carmeliet G, Schipani E. Hypoxia-driven pathways in bone development, regeneration and disease. Nat Rev Rheumatol. 2012;8(6):358–66.  https://doi.org/10.1038/nrrheum.2012.36.CrossRefPubMedGoogle Scholar
  31. 31.
    Simon MC, Keith B. The role of oxygen availability in embryonic development and stem cell function. Nat Rev Mol Cell Biol. 2008;9(4):285–96.  https://doi.org/10.1038/nrm2354.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov. 2011;10(10):767–77.  https://doi.org/10.1038/nrd3554.CrossRefPubMedGoogle Scholar
  33. 33.
    Parks SK, Chiche J, Pouyssegur J. Disrupting proton dynamics and energy metabolism for cancer therapy. Nat Rev Cancer. 2013;13(9):611–23.  https://doi.org/10.1038/nrc3579.CrossRefPubMedGoogle Scholar
  34. 34.
    Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000;289(5484):1504–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584–93.  https://doi.org/10.1038/nrc867. CrossRefPubMedGoogle Scholar
  36. 36.
    Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350(16):1655–64.  https://doi.org/10.1056/NEJMra030831.CrossRefPubMedGoogle Scholar
  37. 37.
    Weilbaecher KN, Guise TA, McCauley LK. Cancer to bone: a fatal attraction. Nat Rev Cancer. 2011;11(6):411–25.  https://doi.org/10.1038/nrc3055.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Yoneda T, Hiraga T. Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun. 2005;328(3):679–87.  https://doi.org/10.1016/j.bbrc.2004.11.070.CrossRefPubMedGoogle Scholar
  39. 39.
    Cleeland CS, Body JJ, Stopeck A, von Moos R, Fallowfield L, Mathias SD, et al. Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid. Cancer. 2013;119(4):832–8.  https://doi.org/10.1002/cncr.27789.CrossRefPubMedGoogle Scholar
  40. 40.
    • von Moos R, Costa L, Ripamonti CI, Niepel D, Santini D. Improving quality of life in patients with advanced cancer: targeting metastatic bone pain. Eur J Cancer. 2017;71:80–94.  https://doi.org/10.1016/j.ejca.2016.10.021. This review paper describes the impact of CABP and how adequate management of CABP can optimize the quality of life in cancer patients CrossRefGoogle Scholar
  41. 41.
    Terpos E, Christoulas D, Gavriatopoulou M. Biology and treatment of myeloma related bone disease. Metabolism, 2017.  https://doi.org/10.1016/j.metabol.2017.11.012, 2018.
  42. 42.
    Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, et al. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med. 2000;6(5):521–8.  https://doi.org/10.1038/74999. CrossRefPubMedGoogle Scholar
  43. 43.
    Qin A, Cheng TS, Pavlos NJ, Lin Z, Dai KR, Zheng MH. V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption. Int J Biochem Cell Biol. 2012;44(9):1422–35.  https://doi.org/10.1016/j.biocel.2012.05.014.CrossRefPubMedGoogle Scholar
  44. 44.
    • Maeda H, Kowada T, Kikuta J, Furuya M, Shirazaki M, Mizukami S, et al. Real-time intravital imaging of pH variation associated with osteoclast activity. Nat Chem Biol. 2016;12(8):579–85.  https://doi.org/10.1038/nchembio.2096. This study introduces a new technique that allows quantitation of osteoclast activity and time-lapse imaging of its in vivo function during bone resorption using intravital imaging by two-photon excitation microscopy together with small fluorescent functional probes CrossRefPubMedGoogle Scholar
  45. 45.
    Henriksen K, Sorensen MG, Jensen VK, Dziegiel MH, Nosjean O, Karsdal MA. Ion transporters involved in acidification of the resorption lacuna in osteoclasts. Calcif Tissue Int. 2008;83(3):230–42.  https://doi.org/10.1007/s00223-008-9168-8.CrossRefPubMedGoogle Scholar
  46. 46.
    Nagae M, Hiraga T, Wakabayashi H, Wang L, Iwata K, Yoneda T. Osteoclasts play a part in pain due to the inflammation adjacent to bone. Bone. 2006;39(5):1107–15.  https://doi.org/10.1016/j.bone.2006.04.033.CrossRefPubMedGoogle Scholar
  47. 47.
    Marelli S, Pace F. Rabeprazole for the treatment of acid-related disorders. Expert Rev Gastroenterol Hepatol. 2012;6(4):423–35.  https://doi.org/10.1586/egh.12.18.CrossRefPubMedGoogle Scholar
  48. 48.
    •• Peppicelli S, Andreucci E, Ruzzolini J, Laurenzana A, Margheri F, Fibbi G, et al. The acidic microenvironment as a possible niche of dormant tumor cells. Cell Mol Life Sci. 2017;74(15):2761–71.  https://doi.org/10.1007/s00018-017-2496-y. This paper describes the critical role of acidity of cancer environment in stimulation of chemo- and radio-resistance, suppression of host immuno-surveilance, establishment of dormancy, and prognosis of cancer patients CrossRefPubMedGoogle Scholar
  49. 49.
    Doherty JR, Cleveland JL. Targeting lactate metabolism for cancer therapeutics. J Clin Invest. 2013;123(9):3685–92.  https://doi.org/10.1172/jci69741.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Halestrap AP. Monocarboxylic acid transport. Compr Physiol. 2013;3(4):1611–43.  https://doi.org/10.1002/cphy.c130008. CrossRefPubMedGoogle Scholar
  51. 51.
    Bergersen LH. Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle. Neuroscience. 2007;145(1):11–9.  https://doi.org/10.1016/j.neuroscience.2006.11.062.CrossRefPubMedGoogle Scholar
  52. 52.
    Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, et al. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 2011;144(5):810–23.  https://doi.org/10.1016/j.cell.2011.02.018.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Gregory NS, Whitley PE, Sluka KA. Effect of intramuscular protons, lactate, and ATP on muscle hyperalgesia in rats. PLoS One. 2015;10(9):e0138576.  https://doi.org/10.1371/journal.pone.0138576.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Holzer P. Acid sensing by visceral afferent neurones. Acta Physiol (Oxf). 2011;201(1):63–75.  https://doi.org/10.1111/j.1748-1716.2010.02143.x.CrossRefGoogle Scholar
  55. 55.
    Deval E, Gasull X, Noel J, Salinas M, Baron A, Diochot S, et al. Acid-sensing ion channels (ASICs): pharmacology and implication in pain. Pharmacol Ther. 2010;128(3):549–58.  https://doi.org/10.1016/j.pharmthera.2010.08.006.CrossRefPubMedGoogle Scholar
  56. 56.
    Olson TH, Riedl MS, Vulchanova L, Ortiz-Gonzalez XR, Elde R. An acid sensing ion channel (ASIC) localizes to small primary afferent neurons in rats. Neuroreport. 1998;9(6):1109–13.CrossRefPubMedGoogle Scholar
  57. 57.
    Jahr H, van Driel M, van Osch GJ, Weinans H, van Leeuwen JP. Identification of acid-sensing ion channels in bone. Biochem Biophys Res Commun. 2005;337(1):349–54.  https://doi.org/10.1016/j.bbrc.2005.09.054.CrossRefPubMedGoogle Scholar
  58. 58.
    Wemmie JA, Taugher RJ, Kreple CJ. Acid-sensing ion channels in pain and disease. Nat Rev Neurosci. 2013;14(7):461–71.  https://doi.org/10.1038/nrn3529.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Sun WH, Chen CC. Roles of proton-sensing receptors in the transition from acute to chronic pain. J Dent Res. 2016;95(2):135–42.  https://doi.org/10.1177/0022034515618382.CrossRefPubMedGoogle Scholar
  60. 60.
    Sluka KA, Price MP, Breese NM, Stucky CL, Wemmie JA, Welsh MJ. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain. 2003;106(3):229–39.CrossRefPubMedGoogle Scholar
  61. 61.
    Karczewski J, Spencer RH, Garsky VM, Liang A, Leitl MD, Cato MJ, et al. Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor, APETx2. Br J Pharmacol. 2010;161(4):950–60.  https://doi.org/10.1111/j.1476-5381.2010.00918.x.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, et al. A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J. 2004;23(7):1516–25.  https://doi.org/10.1038/sj.emboj.7600177.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Yu Y, Chen Z, Li WG, Cao H, Feng EG, Yu F, et al. A nonproton ligand sensor in the acid-sensing ion channel. Neuron. 2010;68(1):61–72.  https://doi.org/10.1016/j.neuron.2010.09.001.CrossRefPubMedGoogle Scholar
  64. 64.
    Hsieh WS, Kung CC, Huang SL, Lin SC, Sun WH. TDAG8, TRPV1, and ASIC3 involved in establishing hyperalgesic priming in experimental rheumatoid arthritis. Sci Rep. 2017;7(1):8870.  https://doi.org/10.1038/s41598-017-09200-6. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Qiu F, Wei X, Zhang S, Yuan W, Mi W. Increased expression of acid-sensing ion channel 3 within dorsal root ganglia in a rat model of bone cancer pain. Neuroreport. 2014;25(12):887–93.  https://doi.org/10.1097/wnr.0000000000000182.CrossRefPubMedGoogle Scholar
  66. 66.
    Feldman P, Due MR, Ripsch MS, Khanna R, White FA. The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain. J Neuroinflammation. 2012;9:180.  https://doi.org/10.1186/1742-2094-9-180.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Kawasaki Y, Kohno T, Zhuang ZY, Brenner GJ, Wang H, Van Der Meer C, et al. Ionotropic and metabotropic receptors, protein kinase A, protein kinase C, and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization. J Neurosci. 2004;24(38):8310–21.  https://doi.org/10.1523/jneurosci.2396-04.2004.CrossRefPubMedGoogle Scholar
  68. 68.
    Mamet J, Baron A, Lazdunski M, Voilley N. Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J Neurosci. 2002;22(24):10662–70.CrossRefPubMedGoogle Scholar
  69. 69.
    Marra S, Ferru-Clement R, Breuil V, Delaunay A, Christin M, Friend V, et al. Non-acidic activation of pain-related acid-sensing ion channel 3 by lipids. EMBO J. 2016;35(4):414–28.  https://doi.org/10.15252/embj.201592335.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288(5464):306–13.CrossRefPubMedGoogle Scholar
  71. 71.
    Lieben L, Carmeliet G. The involvement of TRP channels in bone homeostasis. Front Endocrinol (Lausanne). 2012;3:99.  https://doi.org/10.3389/fendo.2012.00099.Google Scholar
  72. 72.
    Ghilardi JR, Rohrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, et al. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci. 2005;25(12):3126–31.  https://doi.org/10.1523/jneurosci.3815-04.2005.CrossRefPubMedGoogle Scholar
  73. 73.
    Niiyama Y, Kawamata T, Yamamoto J, Omote K, Namiki A. Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons. Neuroscience. 2007;148(2):560–72.  https://doi.org/10.1016/j.neuroscience.2007.05.049.CrossRefPubMedGoogle Scholar
  74. 74.
    Niiyama Y, Kawamata T, Yamamoto J, Furuse S, Namiki A. SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain. Br J Anaesth. 2009;102(2):251–8.  https://doi.org/10.1093/bja/aen347.CrossRefPubMedGoogle Scholar
  75. 75.
    Nakanishi M, Hata K, Nagayama T, Sakurai T, Nishisho T, Wakabayashi H, et al. Acid activation of Trpv1 leads to an up-regulation of calcitonin gene-related peptide expression in dorsal root ganglion neurons via the CaMK-CREB cascade: a potential mechanism of inflammatory pain. Mol Biol Cell. 2010;21(15):2568–77.  https://doi.org/10.1091/mbc.E10-01-0049.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Xu Q, Zhang XM, Duan KZ, Gu XY, Han M, Liu BL, et al. Peripheral TGF-beta1 signaling is a critical event in bone cancer-induced hyperalgesia in rodents. J Neurosci. 2013;33(49):19099–111.  https://doi.org/10.1523/jneurosci.4852-12.2013.CrossRefPubMedGoogle Scholar
  77. 77.
    Li Y, Cai J, Han Y, Xiao X, Meng XL, Su L, et al. Enhanced function of TRPV1 via up-regulation by insulin-like growth factor-1 in a rat model of bone cancer pain. Eur J Pain. 2014;18(6):774–84.  https://doi.org/10.1002/j.1532-2149.2013.00420.x.CrossRefPubMedGoogle Scholar
  78. 78.
    Riera CE, Huising MO, Follett P, Leblanc M, Halloran J, Van Andel R, et al. TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling. Cell. 2014;157(5):1023–36.  https://doi.org/10.1016/j.tem.2016.03.007. CrossRefPubMedGoogle Scholar
  79. 79.
    • Riera CE, Dillin A. Emerging role of sensory perception in aging and metabolism. Trends Endocrinol Metab. 2016;27(5):294–303.  https://doi.org/10.1016/j.cell.2014.03.051. This paper overviews the results of recent genetic studies using TRPV1 −/− mice that showed that sensory perception plays a role in influencing energy homeostasis and longevity CrossRefPubMedGoogle Scholar
  80. 80.
    Moran MM. TRP channels as potential drug targets. Annu Rev Pharmacol Toxicol. 2018;58:309–30.  https://doi.org/10.1146/annurev-pharmtox-010617-052832.CrossRefPubMedGoogle Scholar
  81. 81.
    Jardin I, Lopez JJ, Diez R, Sanchez-Collado J, Cantonero C, Albarran L, et al. TRPs in pain sensation. Front Physiol. 2017;8:392.  https://doi.org/10.3389/fphys.2017.00392.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355–84.  https://doi.org/10.1146/annurev-cellbio-101011-155833.CrossRefPubMedGoogle Scholar
  83. 83.
    Brederson JD, Kym PR, Szallasi A. Targeting TRP channels for pain relief. Eur J Pharmacol. 2013;716(1–3):61–76.  https://doi.org/10.1016/j.ejphar.2013.03.003.CrossRefPubMedGoogle Scholar
  84. 84.
    Dalal S, Bruera E. Access to opioid analgesics and pain relief for patients with cancer. Nat Rev Clin Oncol. 2013;10(2):108–16.  https://doi.org/10.1038/nrclinonc.2012.237.CrossRefPubMedGoogle Scholar
  85. 85.
    Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with the use of morphine and opiates. J Intern Med. 2006;260(1):76–87.  https://doi.org/10.1111/j.1365-2796.2006.01667.x.CrossRefPubMedGoogle Scholar
  86. 86.
    Ballantyne JC, LaForge KS. Opioid dependence and addiction during opioid treatment of chronic pain. Pain. 2007;129(3):235–55.  https://doi.org/10.1016/j.pain.2007.03.028. CrossRefPubMedGoogle Scholar
  87. 87.
    Garami A, Ibrahim M, Gilbraith K, Khanna R, Pakai E, Miko A, et al. Transient receptor potential vanilloid 1 antagonists prevent anesthesia-induced hypothermia and decrease postincisional opioid dose requirements in rodents. Anesthesiology. 2017;127(5):813–23.  https://doi.org/10.1097/aln.0000000000001812.CrossRefPubMedGoogle Scholar
  88. 88.
    Gillies RJ, Verduzco D, Gatenby RA. Evolutionary dynamics of carcinogenesis and why targeted therapy does not work. Nat Rev Cancer. 2012;12(7):487–93.  https://doi.org/10.1038/nrc3298.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Nishisho T, Hata K, Nakanishi M, Morita Y, Sun-Wada GH, Wada Y, et al. The a3 isoform vacuolar type H(+)-ATPase promotes distant metastasis in the mouse B16 melanoma cells. Mol Cancer Res. 2011;9(7):845–55.  https://doi.org/10.1158/1541-7786.mcr-10-0449. CrossRefPubMedGoogle Scholar
  90. 90.
    McGuire C, Cotter K, Stransky L, Forgac M. Regulation of V-ATPase assembly and function of V-ATPases in tumor cell invasiveness. Biochim Biophys Acta. 2016;1857(8):1213–8.  https://doi.org/10.1016/j.bbabio.2016.02.010.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Liebig C, Ayala G, Wilks J, Verstovsek G, Liu H, Agarwal N, et al. Perineural invasion is an independent predictor of outcome in colorectal cancer. J Clin Oncol. 2009;27(31):5131–7.  https://doi.org/10.1200/JCO.2009.22.4949.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Magnon C, Hall SJ, Lin J, Xue X, Gerber L, Freedland SJ, et al. Autonomic nerve development contributes to prostate cancer progression. Science. 2013;341(6142):1236361.  https://doi.org/10.1126/science.1236361.CrossRefPubMedGoogle Scholar
  93. 93.
    Saloman JL, Albers KM, Li D, Hartman DJ, Crawford HC, Muha EA, et al. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer. Proc Natl Acad Sci U S A. 2016;113(11):3078–83.  https://doi.org/10.1073/pnas.1512603113.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Chatzistefanou I, Lubek J, Markou K, Ord RA. The role of perineural invasion in treatment decisions for oral cancer patients: a review of the literature. J Cranio-Maxillofac Surg. 2017;45(6):821–5.  https://doi.org/10.1016/j.jcms.2017.02.022.CrossRefGoogle Scholar
  95. 95.
    Yoneda T, Hiasa M, Nagata Y, Okui T, White FA. Acidic microenvironment and bone pain in cancer-colonized bone. Bonekey Rep. 2015;4:690.  https://doi.org/10.1038/bonekey.2015.58.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiochemistryOsaka University Graduate School of DentistryOsakaJapan
  2. 2.Department of Biomaterials and BioengineeringsUniversity of Tokushima Graduate SchoolTokushimaJapan
  3. 3.Department of Oral and Maxillofacial Surgery and BiopathologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan

Personalised recommendations