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Current Neuropharmacology



ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors

Author(s): Pablo Romero-Morelos, Erika Ruvalcaba-Paredes, David Garciadiego-Cázares, Martín Pérez-Santos, Samuel Reyes-Long, Alfonso Alfaro-Rodriguez, Mauricio Salcedo, Javier Mancilla-Ramírez and Cindy Bandala*

Volume 19 , Issue 3 , 2021

Published on: 11 November, 2020

Page: [308 - 319] Pages: 12

DOI: 10.2174/1570159X18666201111112748

Price: $65


Background: Primary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel therapeutic approaches in this field.

Aim: This study aims to identify the neurophysiology of the mechanisms related to pain management in bone tumors.

Methods: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index to get information about the neurophysiology mechanisms related to pain management in bone tumors.

Results: The central and peripheral mechanisms that promote bone cancer pain are poorly understood. Studies have shown that bone cancer could be related to neurochemicals produced by tumor and inflammatory cells, coupled with peripheral sensitization due to nerve compression and injury caused by tumor growth. The activity of mesolimbic dopaminergic neurons, substance P, cysteine/ glutamate antiporter, and other neurochemical dynamics brings us putative strategies to suggest better and efficient treatments against pain in cancer patients.

Conclusion: Cancer-induced bone pain could include neuropathic and inflammatory pain, but with different modifications to the periphery tissue, nerves and neurochemical changes in different neurological levels. In this sense, we explore opportunity areas in pharmacological and nonpharmacological pain management, according to pain-involved mechanisms in this study.

Keywords: Bone pain, treatment, nociceptive, neuropathic, neurological mechanism, novel management.

Graphical Abstract
Merskey, H.; Albe Fessard, D.; Bonica, J.J.; Carmon, A.; Dubner, R.; Kerr, F.W.L.; Lindblom, U.; Mumford, J.M.; Nathan, P.W.; Noordenbos, W.; Pagni, C.A.; Renaer, M.J.; Sternbach, R.A.; Sunderland, S. Recommended by the IASP Subcommittee on Taxonomy. Pain terms: a list with definitions and notes on usage. Pain, 1979, 6(3), 249-252.
[PMID: 460932]
Khosravi, S.P.; del Castillo, R.A.; Pérez, M.G. Manejo del dolor oncológico. An. Med. Interna (Madrid), 2007, 24, 554-557.
Williams, A.C.; Craig, K.D. Updating the definition of pain. Pain, 2016, 157(11), 2420-2423.
[] [PMID: 27200490]
Bernstein, L.R. A pragmatic, general definition of pain. Pain Rep., 2020, 5(2)e813
[] [PMID: 32441702]
Havelin, J.; King, T. Mechanisms underlying bone and joint pain. Curr. Osteoporos. Rep., 2018, 16(6), 763-771.
[] [PMID: 30370434]
Solans, M.; Chan, D.S.M.; Mitrou, P.; Norat, T.; Romaguera, D. A systematic review and meta-analysis of the 2007 WCRF/AICR score in relation to cancer-related health outcomes. Ann. Oncol., 2020, 31(3), 352-368.
[] [PMID: 32067678]
Money, S.; Garber, B. Management of cancer pain. Curr. Emerg. Hosp. Med. Rep., 2018, 6, 141-146.
Mantyh, P.W. Cancer pain and its impact on diagnosis, survival and quality of life. Nat. Rev. Neurosci., 2006, 7(10), 797-809.
[] [PMID: 16988655]
Candido, K.D.; Kusper, T.M.; Knezevic, N.N. New Cancer Pain Treatment Options. Curr. Pain Headache Rep., 2017, 21(2), 12.
[] [PMID: 28265859]
DelaGarza-Montano, P.; Estrada-Villaseñor, E.; Dominguez, R.R.; Martinez-Lopez, V.; Avila-Luna, A.; Alfaro-Rodriguez, A.; Garciadiego-Cazares, D.; Carlos, A.; Hernandez-Perez, A.D.; Bandala, C. Epidemiological Aspects of osteosarcoma, giant cell tumor and chondrosarcoma musculoskeletal tumors--experience of the National Rehabilitation Institute, Mexico City. Asian Pac. J. Cancer Prev., 2015, 16(15), 6451-6455.
[] [PMID: 26434858]
Marko, T.A.; Diessner, B.J.; Spector, L.G. Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison. Pediatr. Blood Cancer, 2016, 63(6), 1006-1011.
[] [PMID: 26929018]
Yoneda, T.; Hiasa, M.; Okui, T. Crosstalk between sensory nerves and cancer in bone. Curr. Osteoporos. Rep., 2018, 16(6), 648-656.
[] [PMID: 30343404]
Orr, P.M.; Shank, B.C.; Black, A.C. The role of pain classification systems in pain management. Crit. Care Nurs. Clin. North Am., 2017, 29(4), 407-418.
[] [PMID: 29107304]
European Commission Health in the European Union: Special EUROBAROMETER. 2007.
Cervero, F.; Laird, J.M.A. Visceral pain. Lancet, 1999, 353(9170), 2145-2148.
[] [PMID: 10382712]
Bouhassira, D. Neuropathic pain: Definition, assessment and epidemiology. Rev. Neurol. (Paris), 2019, 175(1-2), 16-25.
[] [PMID: 30385075]
Carr, D.B.; Goudas, L.C. Acute pain. Lancet, 1999, 353(9169), 2051-2058.
Wurhman, E.; Cooney, M.F. Acute pain: assessment and treatment. Medscape, 2011.
Hylands-White, N.; Duarte, R.V.; Raphael, J.H. An overview of treatment approaches for chronic pain management. Rheumatol. Int., 2017, 37(1), 29-42.
[] [PMID: 27107994]
IASP. Part III: Pain Terms, A Current List with Definitions and Notes on Usage. Classification of Chronic Pain, Second Edition, IASP Task Force on Taxonomy, edited by H. Merskey and N. Bogduk, ISAP Press, Seattle, 1994, 209-214.
Loeser, J.D.; Melzack, R. Pain: an overview. Lancet, 1999, 353(9164), 1607-1609.
von Baeyer, C.L. Children’s self-reports of pain intensity: scale selection, limitations and interpretation. Pain Res. Manag., 2006, 11(3), 157-162.
[] [PMID: 16960632]
Hester, N.; Foster, R.; Kristensen, K. Measurement of pain in children: Generalizability and validity of the Pain Ladder and the Poker Chip Tool. Tyler D, Krane E, eds. Pediatric Pain, Vol 15: Advances in Pain Research and Therapy; New York: Raven Press, 1990, pp. 79-84
Mahon, P.; Holsti, L.; Siden, H.; Strahlendorf, C.; Turnham, L.; Giaschi, D. Using colors to assess pain in toddlers: validation of “the rainbow pain scale”-a proof-of-principle study. J. Pediatr. Oncol. Nurs., 2015, 32(1), 40-46.
[] [PMID: 25416519]
Hicks, C.L.; von Baeyer, C.L.; Spafford, P.A.; van Korlaar, I.; Goodenough, B. The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain, 2001, 93(2), 173-183.
[] [PMID: 11427329]
Cline, M.E.; Herman, J.; Shaw, E.R.; Morton, R.D. Standardization of the visual analogue scale. Nurs. Res., 1992, 41(6), 378-380.
[] [PMID: 1437591]
von Baeyer, C.L.; Spagrud, L.J.; McCormick, J.C.; Choo, E.; Neville, K.; Connelly, M.A. Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for children’s self-reports of pain intensity. Pain, 2009, 143(3), 223-227.
[] [PMID: 19359097]
Pagé, M.G.; Katz, J.; Stinson, J.; Isaac, L.; Martin-Pichora, A.L.; Campbell, F. Validation of the numerical rating scale for pain intensity and unpleasantness in pediatric acute postoperative pain: sensitivity to change over time. J. Pain, 2012, 13(4), 359-369.
[] [PMID: 22424915]
Tesler, M.D.; Savedra, M.C.; Holzemer, W.L.; Wilkie, D.J.; Ward, J.A.; Paul, S.M. The word-graphic rating scale as a measure of children’s and adolescents’ pain intensity. Res. Nurs. Health, 1991, 14(5), 361-371.
[] [PMID: 1891622]
Haefeli, M.; Elfering, A. Pain assessment. Eur. Spine J., 2006, 15(1), 17-24.
Vicente, H.M.T.; Delgado, B.S.; Bandrés, M.F.; Ramírez, I.; de la Torre, M.V.; Capdevila, G.L. Valoración del dolor. revisión comparativa de escalas y cuestionarios. Rev. Soc. Esp. Dolor, 2018, 25(4), 228-236.
Besson, J.M. The neurobiology of pain. Lancet, 1999, 353(9164), 1610-1615.
Pergolizzi, J.; Ahlbeck, K.; Aldington, D.; Alon, E.; Coluzzi, F.; Dahan, A.; Huygen, F.; Kocot-Kępska, M.; Mangas, A.C.; Mavrocordatos, P.; Morlion, B.; Müller-Schwefe, G.; Nicolaou, A.; Pérez Hernández, C.; Sichère, P.; Schäfer, M.; Varrassi, G. The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment. Curr. Med. Res. Opin., 2013, 29(9), 1127-1135.
[] [PMID: 23786498]
Payne, R. Anatomy, physiology, and neuropharmacology of cancer pain. Med. Clin. North Am., 1987, 71(2), 153-167.
[] [PMID: 3546978]
Chwistek, M. Recent advances in understanding and managing cancer pain. F1000 Res., 2017, 6, 945.
Mancino, M.; Ametller, E.; Gascón, P.; Almendro, V. The neuronal influence on tumor progression. Biochim. Biophys. Acta, 2011, 1816(2), 105-118.
[PMID: 21616127]
Patel, M.K.; Kaye, A.D.; Urman, R.D. Tanezumab: Therapy targeting nerve growth factor in pain pathogenesis. J. Anaesthesiol. Clin. Pharmacol., 2018, 34(1), 111-116.
[PMID: 29643634]
Miller, K.E.; Hoffman, E.M.; Sutharshan, M.; Schechter, R. Glutamate pharmacology and metabolism in peripheral primary afferents: physiological and pathophysiological mechanisms. Pharmacol. Ther., 2011, 130(3), 283-309.
[] [PMID: 21276816]
Du, X.; Li, J.; Li, M.; Yang, X.; Qi, Z.; Xu, B.; Liu, W.; Xu, Z.; Deng, Y. Research progress on the role of type I vesicular glutamate transporter (VGLUT1) in nervous system diseases. Cell Biosci., 2020, 10, 26.
[] [PMID: 32158532]
Nencini, S.; Ringuet, M.; Kim, D.H.; Chen, Y.J.; Greenhill, C.; Ivanusic, J.J. Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain. Mol. Pain, 2017, 131744806917697011
[] [PMID: 28326938]
Mantyh, P.W. The neurobiology of skeletal pain. Eur. J. Neurosci., 2014, 39(3), 508-519.
[] [PMID: 24494689]
Castañeda-Corral, G.; Jimenez-Andrade, J.M.; Bloom, A.P.; Taylor, R.N.; Mantyh, W.G.; Kaczmarska, M.J.; Ghilardi, J.R.; Mantyh, P.W. The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience, 2011, 178, 196-207.
[] [PMID: 21277945]
Jimenez-Andrade, J.M.; Mantyh, W.G.; Bloom, A.P.; Ferng, A.S.; Geffre, C.P.; Mantyh, P.W. Bone cancer pain. Ann. N. Y. Acad. Sci., 2010, 1198, 173-181.
[] [PMID: 20536932]
Hiasa, M.; Okui, T.; Allette, Y.M.; Ripsch, M.S.; Sun-Wada, G.H.; Wakabayashi, H.; Roodman, G.D.; White, F.A.; Yoneda, T. Bone pain induced by multiple myeloma is reduced by targeting V-ATPase and ASIC3. Cancer Res., 2017, 77(6), 1283-1295.
[] [PMID: 28254863]
Argyriou, A.A.; Cavaletti, G.; Bruna, J.; Kyritsis, A.P.; Kalofonos, H.P. Bortezomib-induced peripheral neurotoxicity: an update. Arch. Toxicol., 2014, 88(9), 1669-1679.
[] [PMID: 25069804]
Schutzer-Weissmann, J.; Farquhar-Smith, P. Post-herpetic neuralgia - a review of current management and future directions. Expert Opin. Pharmacother., 2017, 18(16), 1739-1750.
[] [PMID: 29025327]
Coluzzi, F.; Di Bussolo, E.; Mandatori, I.; Mattia, C. Bone metastatic disease: taking aim at new therapeutic targets. Curr. Med. Chem., 2011, 18(20), 3093-3115.
[] [PMID: 21651483]
Berenson, J.R.; Lichtenstein, A.; Porter, L.; Dimopoulos, M.A.; Bordoni, R.; George, S.; Lipton, A.; Keller, A.; Ballester, O.; Kovacs, M.J.; Blacklock, H.A.; Bell, R.; Simeone, J.; Reitsma, D.J.; Heffernan, M.; Seaman, J.; Knight, R.D. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. N. Engl. J. Med., 1996, 334(8), 488-493.
[] [PMID: 8559201]
Rosen, L.S.; Gordon, D.; Kaminski, M.; Howell, A.; Belch, A.; Mackey, J.; Apffelstaedt, J.; Hussein, M.; Coleman, R.E.; Reitsma, D.J.; Seaman, J.J.; Chen, B.L.; Ambros, Y. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J., 2001, 7(5), 377-387.
[PMID: 11693896]
Gimsing, P.; Carlson, K.; Turesson, I.; Fayers, P.; Waage, A.; Vangsted, A.; Mylin, A.; Gluud, C.; Juliusson, G.; Gregersen, H.; Hjorth-Hansen, H.; Nesthus, I.; Dahl, I.M.; Westin, J.; Nielsen, J.L.; Knudsen, L.M.; Ahlberg, L.; Hjorth, M.; Abildgaard, N.; Andersen, N.F.; Linder, O.; Wisløff, F. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial. Lancet Oncol., 2010, 11(10), 973-982.
[] [PMID: 20863761]
Lipton, A.; Jun, S. RANKL inhibition in the treatment of bone metastases. Curr. Opin. Support. Palliat. Care, 2008, 2(3), 197-203.
[] [PMID: 18685421]
Body, J.J.; Facon, T.; Coleman, R.E.; Lipton, A.; Geurs, F.; Fan, M.; Holloway, D.; Peterson, M.C.; Bekker, P.J. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin. Cancer Res., 2006, 12(4), 1221-1228.
[] [PMID: 16489077]
Halvorson, K.G.; Kubota, K.; Sevcik, M.A.; Lindsay, T.H.; Sotillo, J.E.; Ghilardi, J.R.; Rosol, T.J.; Boustany, L.; Shelton, D.L.; Mantyh, P.W. A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone. Cancer Res., 2005, 65(20), 9426-9435.
[] [PMID: 16230406]
Sevcik, M.A.; Ghilardi, J.R.; Peters, C.M.; Lindsay, T.H.; Halvorson, K.G.; Jonas, B.M.; Kubota, K.; Kuskowski, M.A.; Boustany, L.; Shelton, D.L.; Mantyh, P.W. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain, 2005, 115(1-2), 128-141.
[] [PMID: 15836976]
Sjölund, K.F.; Yang, R.; Lee, K.H.; Resnick, M. Randomized study of pregabalin in patients with cancer-induced bone pain. Pain Ther., 2013, 2(1), 37-48.
[] [PMID: 25135035]
Lim, F.M.Y.; Bobrowski, A.; Agarwal, A.; Silva, M.F. Use of corticosteroids for pain control in cancer patients with bone metastases: a comprehensive literature review. Curr. Opin. Support. Palliat. Care, 2017, 11(2), 78-87.
[] [PMID: 28306570]
Kumar, A.; Weber, M.H.; Gokaslan, Z.; Wolinsky, J.P.; Schmidt, M.; Rhines, L.; Fehlings, M.G.; Laufer, I.; Sciubba, D.M.; Clarke, M.J.; Sundaresan, N.; Verlaan, J.J.; Sahgal, A.; Chou, D.; Fisher, C.G. Metastatic spinal cord compression and steroid treatment: a systematic review. Clin. Spine Surg., 2017, 30(4), 156-163.
[] [PMID: 28437329]
Fallon, M.; Giusti, R.; Aielli, F.; Hoskin, P.; Rolke, R.; Sharma, M.; Ripamonti, C.I. ESMO Guidelines Committee. Management of cancer pain in adult patients. ESMO Clinical Practice Guidelines. Ann. Oncol., 2018, 29, iv166-iv191.
Corder, G.; Castro, D.C.; Bruchas, M.R.; Scherrer, G. Endogenous and exogenous opioids in pain. Annu. Rev. Neurosci., 2018, 41, 453-473.
[] [PMID: 29852083]
Ferdousi, M.; Finn, D.P. Stress-induced modulation of pain: Role of the endogenous opioid system. In: Prog. Brain Res; , 2018; 239, pp. 121-177.
[] [PMID: 30314566]
Law, P.Y.; Wong, Y.H.; Loh, H.H. Molecular mechanisms and regulation of opioid receptor signaling. Annu. Rev. Pharmacol. Toxicol., 2000, 40, 389-430.
[] [PMID: 10836142]
Coluzzi, F.; Raffa, R.B.; Pergolizzi, J.; Rocco, A.; Locarini, P.; Cenfra, N.; Cimino, G.; Mattia, C. Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease. J. Pain Res., 2015, 8, 229-238.
[] [PMID: 26064064]
Coluzzi, F.; Pergolizzi, J.; Raffa, R.B.; Mattia, C. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism. Ther. Clin. Risk Manag., 2015, 11, 515-523.
[] [PMID: 25848298]
Coluzzi, F. Assessing and treating chronic pain in patients with end-stage renal disease. Drugs, 2018, 78(14), 1459-1479.
[] [PMID: 30206801]
Kim, J.W.; Min, C.K.; Mun, Y.C.; Park, Y.; Kim, B.S.; Nam, S.H.; Koh, Y.; Kwon, J.H.; Choe, P.G.; Park, W.B.; Kim, I. Varicella-zoster virus-specific cell-mediated immunity and herpes zoster development in multiple myeloma patients receiving bortezomib- or thalidomide-based chemotherapy. J. Clin. Virol., 2015, 73, 64-69.
[] [PMID: 26546878]
Pickering, G.; Martin, E.; Tiberghien, F.; Delorme, C.; Mick, G. Localized neuropathic pain: an expert consensus on local treatments. Drug Des. Devel. Ther., 2017, 11, 2709-2718.
[] [PMID: 29066862]
Ghilardi, J.R.; Röhrich, H.; Lindsay, T.H.; Sevcik, M.A.; Schwei, M.J.; Kubota, K.; Halvorson, K.G.; Poblete, J.; Chaplan, S.R.; Dubin, A.E.; Carruthers, N.I.; Swanson, D.; Kuskowski, M.; Flores, C.M.; Julius, D.; Mantyh, P.W. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J. Neurosci., 2005, 25(12), 3126-3131.
[] [PMID: 15788769]
Anand, P.; Bley, K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br. J. Anaesth., 2011, 107(4), 490-502.
[] [PMID: 21852280]
Moore, D.C.; Pellegrino, A.E. Pegfilgrastim-induced bone pain: a review on incidence, risk factors, and evidence-based management. Ann. Pharmacother., 2017, 51(9), 797-803.
[] [PMID: 28423916]
Xu, H.; Gong, Q.; Vogl, F.D.; Reiner, M.; Page, J.H. Risk factors for bone pain among patients with cancer receiving myelosuppressive chemotherapy and pegfilgrastim. Support. Care Cancer, 2016, 24(2), 723-730.
[] [PMID: 26162536]
Lower, E.E.; Charif, M.; Bartelt, M. Reduced dose pegfilgrastim is associated with less bone pain without increased neutropenia: a retrospective study. Cancer Chemother. Pharmacol., 2018, 82(1), 165-170.
[] [PMID: 29869680]
Kirshner, J.J.; McDonald, M.C., III; Kruter, F.; Guinigundo, A.S.; Vanni, L.; Maxwell, C.L.; Reiner, M.; Upchurch, T.E.; Garcia, J.; Morrow, P.K. NOLAN: a randomized, phase 2 study to estimate the effect of prophylactic naproxen or loratadine vs no prophylactic treatment on bone pain in patients with early-stage breast cancer receiving chemotherapy and pegfilgrastim. Support. Care Cancer, 2018, 26(4), 1323-1334.
[] [PMID: 29147854]
Duggan, C.; Murphy, L.; Costello, V.; Leary, E.O.; Yousif, A.D.; Blazkova, S.; Dowling, M. Oral loratadine in the management of G-CSF-induced bone pain: a pilot study. Br. J. Nurs., 2019, 28(4), S4-S11.
[] [PMID: 30811242]
Gavioli, E.; Abrams, M. Prevention of granulocyte-colony stimulating factor (G-CSF) induced bone pain using double histamine blockade. Support. Care Cancer, 2017, 25(3), 817-822.
[] [PMID: 27817104]
National Library of Medicine (U.S.). Loratadine for the Reduction of G-CSF Induced Bone Pain in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization., 2020. NCT04211259. Available at:
National Library of Medicine (U.S.). Evaluation of Loratadine for G-CSF Induced Bone Pain in Patients With Hematologic Malignancies., 2014. NCT02305979. Available at:
Mhaskar, R.; Kumar, A.; Miladinovic, B.; Djulbegovic, B. Bisphosphonates in multiple myeloma: an updated network meta-analysis. Cochrane Database Syst. Rev., 2017, 12(12)CD003188
[] [PMID: 29253322]
Hoskin, P.; Sundar, S.; Reczko, K.; Forsyth, S.; Mithal, N.; Sizer, B.; Bloomfield, D.; Upadhyay, S.; Wilson, P.; Kirkwood, A.; Stratford, M.; Jitlal, M.; Hackshaw, A. A multicenter randomized trial of ibandronate compared with single-dose radiotherapy for localized metastatic bone pain in prostate cancer. JNCI. J. Natl. Cancer Inst., 2015, 107(10)djv197
[] [PMID: 26242893]
Wang, G.; Chen, J.; Ma, R.; Xu, W.; Yan, C.; Niu, C. Effects of zoledronic acid and ibandronate in the treatment of cancer pain in rats with lung cancer combined with bone metastases. Oncol. Lett., 2018, 16(2), 1696-1700.
[] [PMID: 30008855]
Purnell, H.; Monson, K. Single-Dose local radiation therapy compared with ibandronate in treating patients with localized metastatic bone pain., 2013. Identifier NCT00082927 Available at:
Altundag, K.; Dizdar, O.; Ozsaran, Z.; Ozkok, S.; Saip, P.; Eralp, Y.; Komurcu, S.; Kuzhan, O.; Ozguroglu, M.; Karahoca, M. Phase II study of loading-dose ibandronate treatment in patients with breast cancer and bone metastases suffering from moderate to severe pain. Onkologie, 2012, 35(5), 254-258.
[] [PMID: 22868504]
National Library of Medicine (U.S.). A study to assess the short term efficacy of intravenous ibandronate (bondronat) in participants with metastatic bone pain due to breast cancer., 2015. Identifier NCT02553707. Available at:
National Library of Medicine (U.S.). A study of loading doses of intravenous bondronat (ibandronate) in patients with breast cancer and malignant bone disease., 2014. Identifier NCT00502736. Available at:
National Library of Medicine (U.S.). A study of loading doses of intravenous bondronat (ibandronate) in patients with breast cancer and metastatic bone disease., 2014. Identifier NCT00478270. Available at:
Saad, F.; Eastham, J. Zoledronic Acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer. Urology, 2010, 76(5), 1175-1181.
[] [PMID: 21056263]
Choi, J.; Lee, E.J.; Yang, S.H. Im, Y.R.; Seong, J. A prospective Phase II study for the efficacy of radiotherapy in combination with zoledronic acid in treating painful bone metastases from gastrointestinal cancers. J. Radiat. Res. (Tokyo), 2019, 60(2), 242-248.
[] [PMID: 30445597]
National Library of Medicine (U.S.). Study comparing full-dose radiotherapy versus reduced dose in the management of bone metastasis in patients with breast cancer receiving zoledronic acid., 2014. Identifier NCT00172029.
National Library of Medicine (U.S.). Efficacy and safety of zoledronic acid in the treatment of bone metastases-related pain in patients with prostate cancer (TRAPEZE)., 2017. Identifier NCT00375648. Available at:
National Library of Medicine (U.S.). A study to assess the efficacy of intravenous/oral bondronat (ibandronate) in patients with metastatic bone disease experiencing moderate to severe pain., 2017. Identifier NCT00099177. Available at:
National Library of Medicine (U.S.). Study to assess the efficacy of intravenous bondronat (ibandronate) in patients with malignant and painful bone disease., 2017. Identifier NCT00099203. Available at:
Brown, D.C.; Agnello, K.; Iadarola, M.J. Intrathecal resiniferatoxin in a dog model: efficacy in bone cancer pain. Pain, 2015, 156(6), 1018-1024.
[] [PMID: 25659068]
Danson, S.; Mulvey, M.R.; Turner, L.; Horsman, J.; Escott, K.; Coleman, R.E.; Ahmedzai, S.H.; Bennett, M.I.; Andrew, D. An exploratory randomized-controlled trial of the efficacy of the Src-kinase inhibitor saracatinib as a novel analgesic for cancer-induced bone pain. J. Bone Oncol., 2019, 19100261
[] [PMID: 31667062]
Fallon, M.; Hoskin, P.J.; Colvin, L.A.; Fleetwood-Walker, S.M.; Adamson, D.; Byrne, A.; Laird, B.J. Randomized double-blind trial of pregabalin versus placebo in conjunction with palliative radiotherapy for cancer-induced bone pain. J. Clin. Oncol., 2016, 34(6), 550-556.
Xu, L.; Zhang, Y.; Huang, Y. Advances in the treatment of neuropathic pain. Adv. Exp. Med. Biol., 2016, 904, 117-129.
[] [PMID: 26900067]
Vielhaber, A.; Portenoy, R.K. Advances in cancer pain management. Hematol. Oncol. Clin. North Am., 2002, 16(3), 527-541.
[] [PMID: 12170566]
Mercadante, S. Non pharmacological interventions and non-fentanyl pharmacological treatments for breakthrough cancer pain: A systematic and critical review. Crit. Rev. Oncol. Hematol., 2018, 122, 60-63.
[] [PMID: 29458790]
Portenoy, R.K. Treatment of cancer pain. Lancet, 2011, 25;377(9784), 2236-2247.
Scarborough, B.M.; Smith, C.B. Optimal pain management for patients with cancer in the modern era. CA Cancer J. Clin., 2018, 68(3), 182-196.
[] [PMID: 29603142]
Liu, W.C.; Zheng, Z.X.; Tan, K.H.; Meredith, G.J. Multidimensional treatment of cancer pain. Curr. Oncol. Rep., 2017, 19(2), 10.
[] [PMID: 28220448]
Dipan, P.; Saurabh, D.; Weber, G. Neuromodulation of cancer pain: current concepts and treatment strategies. Topics in Pain Management, 2016, 31(12), 1-10.
Searle, R.D.; Bennett, M.I.; Johnson, M.I.; Callin, S.; Radford, H. Transcutaneous electrical nerve stimulation (TENS) for cancer bone pain. J. Pain Symptom Manage., 2009, 37(3), 424-428.
[] [PMID: 18790599]
Bennett, M.I.; Johnson, M.I.; Brown, S.R.; Radford, H.; Brown, J.M.; Searle, R.D. Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain. J. Pain, 2010, 11(4), 351-359.
[] [PMID: 19853518]
Mokhtari, T.; Ren, Q.; Li, N.; Wang, F.; Bi, Y.; Hu, L. Transcutaneous electrical nerve stimulation in relieving neuropathic pain: basic mechanisms and clinical applications. Curr. Pain Headache Rep., 2020, 24(4), 14.
[] [PMID: 32072323]
Teoli, D.; An, J. Transcutaneous Electrical Nerve Stimulation (TENS). StatPearls; StatPearls Publishing: Treasure Island, FL, 2020.

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