The neurobiology of cancer pain

Neuroscientist

Volumn 20, Issue 5, 2014, Pages 546-562

  Schmidt, Brian L ^a,b  

^a NEW YORK UNIVERSITY COLLEGE OF DENTISTRY   (United States)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

cancer; cancer pain; pain; sensory system; tumor

Indexed keywords

ADENOSINE TRIPHOSPHATE; CANNABINOID; ENDOTHELIN; FORMALDEHYDE; KETAMINE; NEUROTROPHIC FACTOR; OPIATE; PROTEINASE; PROTON;

ACUPUNCTURE; ARTICLE; ASTROCYTE; CANCER PAIN; ELECTROSTIMULATION THERAPY; HUMAN; INFLAMMATORY PAIN; NEUROBIOLOGY; NEUROPATHIC PAIN; NONHUMAN; PAIN RECEPTOR; SENSORY NERVE; SPINAL CORD STIMULATION; TUMOR MICROENVIRONMENT; ANALGESIA; ANIMAL; CLINICAL TRIAL (TOPIC); COMPLICATION; NEOPLASM; PAIN; PATHOPHYSIOLOGY; PROCEDURES;

ANIMALS; CLINICAL TRIALS AS TOPIC; HUMANS; NEOPLASMS; PAIN; PAIN MANAGEMENT;

EID: 84907217224     PISSN: 10738584     EISSN: 10894098     Source Type: Journal    
DOI: 10.1177/1073858414525828     Document Type: Article

References (121)

1. Asai H, Ozaki N, Shinoda M, Nagamine K, Tohnai I, Ueda M. Heat and mechanical hyperalgesia in mice model of cancer pain. Pain. 2005 ; 117: 19-29
2. Bali KK, Venkataramani V, Satagopam VP, Gupta P, Schneider R, Kuner R.. Transcriptional mechanisms underlying sensitization of peripheral sensory neurons by granulocyte-/granulocyte-macrophage colony stimulating factors. Mol Pain. 2013 ; 9: 48
3. Bapat AA, Hostetter G, Von Hoff DD, Han H.. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer. 2011 ; 11: 695-707
4. Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2012 ; 11: CD003351
5. Betourne A, Familiades J, Lacassagne L, Halley H, Cazales M, Ducommun B. Decreased motivational properties of morphine in mouse models of cancerous- or inflammatory-chronic pain: implication of supraspinal neuropeptide FF(2) receptors. Neuroscience. 2008 ; 157: 12-21
6. Bloom AP, Jimenez-Andrade JM, Taylor RN, Castaneda-Corral G, Kaczmarska MJ, Freeman KT. Breast cancer-induced bone remodeling, skeletal pain, and sprouting of sensory nerve fibers. J Pain. 2011 ; 12: 698-711
7. Brener S, Gonzalez-Moles MA, Tostes D, Esteban F, Gil-Montoya JA, Ruiz-Avila I. A role for the substance P/NK-1 receptor complex in cell proliferation in oral squamous cell carcinoma. Anticancer Res. 2009 ; 29: 2323-9
8. Cain DM, Wacnik PW, Turner M, Wendelschafer-Crabb G, Kennedy WR, Wilcox GL. Functional interactions between tumor and peripheral nerve: changes in excitability and morphology of primary afferent fibers in a murine model of cancer pain. J Neurosci. 2001 ; 21: 9367-76
9. Cao L, Liu X, Lin EJ, Wang C, Choi EY, Riban V. Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell. 2010 ; 142: 52-64
10. Chizhmakov I, Mamenko N, Volkova T, Khasabova I, Simone DA, Krishtal O.. P2X receptors in sensory neurons co-cultured with cancer cells exhibit a decrease in opioid sensitivity. Eur J Neurosci. 2009 ; 29: 76-86
11. Constantin CE, Mair N, Sailer CA, Andratsch M, Xu ZZ, Blumer MJ. Endogenous tumor necrosis factor alpha (TNFα) requires TNF receptor type 2 to generate heat hyperalgesia in a mouse cancer model. J Neurosci. 2008 ; 28: 5072-81
12. Curto-Reyes V, Llames S, Hidalgo A, Menendez L, Baamonde A.. Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain. Br J Pharmacol. 2010 ; 160: 561-73
13. Donovan-Rodriguez T, Dickenson AH, Urch CE. Gabapentin normalizes spinal neuronal responses that correlate with behavior in a rat model of cancer-induced bone pain. Anesthesiology. 2005 ; 102: 132-40
14. Donovan-Rodriguez T, Urch CE, Dickenson AH. Evidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain. Neurosci Lett. 2006 ; 393: 237-42
15. Feng F, Yang J, Tong L, Yuan S, Tian Y, Hong L. Substance P immunoreactive nerve fibres are related to gastric cancer differentiation status and could promote proliferation and migration of gastric cancer cells. Cell Biol Int. 2011 ; 35: 623-9
16. Fujita M, Andoh T, Ohashi K, Akira A, Saiki I, Kuraishi Y.. Roles of kinin B1 and B2 receptors in skin cancer pain produced by orthotopic melanoma inoculation in mice. Eur J Pain. 2010 ; 14: 588-94
17. Furuse S, Kawamata T, Yamamoto J, Niiyama Y, Omote K, Watanabe M. Reduction of bone cancer pain by activation of spinal cannabinoid receptor 1 and its expression in the superficial dorsal horn of the spinal cord in a murine model of bone cancer pain. Anesthesiology. 2009 ; 111: 173-86
18. Gao YJ, Cheng JK, Zeng Q, Xu ZZ, Decosterd I, Xu X. Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model. Exp Neurol. 2009 ; 219: 146-55
19. Geis C, Graulich M, Wissmann A, Hagenacker T, Thomale J, Sommer C. Evoked pain behavior and spinal glia activation is dependent on tumor necrosis factor receptor 1 and 2 in a mouse model of bone cancer pain. Neuroscience. 2010 ; 169: 463-74
20. Ghilardi JR, Rohrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci. 2005 ; 25: 3126-31
21. Gilchrist LS, Cain DM, Harding-Rose C, Kov AN, Wendelschafer-Crabb G, Kennedy WR. Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain. Brain Res. 2005 ; 1044: 197-205
22. Gu X, Mei F, Liu Y, Zhang R, Zhang J, Ma Z.. Intrathecal administration of the cannabinoid 2 receptor agonist JWH015 can attenuate cancer pain and decrease mRNA expression of the 2B subunit of N-methyl-d-aspartic acid. Anesth Analg. 2011 ; 113: 405-11
23. Gu X, Zhang J, Ma Z, Wang J, Zhou X, Jin Y. The role of N-methyl-d-aspartate receptor subunit NR2B in spinal cord in cancer pain. Eur J Pain. 2010 ; 14: 496-502
24. Guerrero AV, Quang P, Dekker N, Jordan RC, Schmidt BL. Peripheral cannabinoids attenuate carcinoma-induced nociception in mice. Neurosci Lett. 2008 ; 433: 77-81
25. Hald A, Ding M, Egerod K, Hansen RR, Konradsen D, Jorgensen SG. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain. Pharmacol Biochem Behav. 2008 ; 91: 38-46
26. Hald A, Hansen RR, Thomsen MW, Ding M, Croucher PI, Gallagher O. Cancer-induced bone loss and associated pain-related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE-10790. Int J Cancer. 2009 ; 125: 1177-85
27. Hald A, Nedergaard S, Hansen RR, Ding M, Heegaard AM. Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain. Eur J Pain. 2009 ; 13: 138-45
28. Halvorson KG, Kubota K, Sevcik MA, Lindsay TH, Sotillo JE, Ghilardi JR. A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone. Cancer Res. 2005 ; 65: 9426-35
29. Halvorson KG, Sevcik MA, Ghilardi JR, Sullivan LJ, Koewler NJ, Bauss F. Intravenous ibandronate rapidly reduces pain, neurochemical indices of central sensitization, tumor burden, and skeletal destruction in a mouse model of bone cancer. J Pain Symptom Manage. 2008 ; 36: 289-303
30. Hamamoto DT, Giridharagopalan S, Simone DA. Acute and chronic administration of the cannabinoid receptor agonist CP 55,940 attenuates tumor-evoked hyperalgesia. Eur J Pharmacol. 2007 ; 558: 73-87
31. Han Y, Li Y, Xiao X, Liu J, Meng XL, Liu FY. Formaldehyde up-regulates TRPV1 through MAPK and PI3K signaling pathways in a rat model of bone cancer pain. Neurosci Bull. 2012 ; 28: 165-72
32. Hang LH, Yang JP, Yin W, Wang LN, Guo F, Ji FH. Activation of spinal TDAG8 and its downstream PKA signaling pathway contribute to bone cancer pain in rats. Eur J Neurosci. 2012 ; 36: 2107-17
33. Hans G, Schmidt BL, Strichartz G.. Nociceptive sensitization by endothelin-1. Brain Res Rev. 2009 ; 60: 36-42
34. Harano N, Ono K, Hidaka K, Kai A, Nakanishi O, Inenaga K.. Differences between orofacial inflammation and cancer pain. J Dent Res. 2010 ; 89: 615-20
35. Hardt M, Lam DK, Dolan JC, Schmidt BL. Surveying proteolytic processes in human cancer microenvironments by microdialysis and activity-based mass spectrometry. Proteomics Clin Appl. 2011 ; 5: 636-43
36. Honore P, Chandran P, Hernandez G, Gauvin DM, Mikusa JP, Zhong C. Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia. Pain. 2009 ; 142: 27-35
37. Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med. 2000 ; 6: 521-8
38. Honore P, Rogers SD, Schwei MJ, Salak-Johnson JL, Luger NM, Sabino MC. Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience. 2000 ; 98: 585-98
39. Hu JH, Wu MY, Tao M, Yang JP.. Changes in protein expression and distribution of spinal CCR2 in a rat model of bone cancer pain. Brain Res. 2013 ; 1509: 1-7
40. Huang JL, Chen XL, Guo C, Wang YX.. Contributions of spinal D-amino acid oxidase to bone cancer pain. Amino Acids. 2012 ; 43: 1905-1918
41. Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP, Malan TP. CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci U S A. 2005 ; 102: 3093-3098
42. Jimenez-Andrade JM, Ghilardi JR, Castaneda-Corral G, Kuskowski MA, Mantyh PW. Preventive or late administration of anti-NGF therapy attenuates tumor-induced nerve sprouting, neuroma formation, and cancer pain. Pain. 2011 ; 152: 2564-74
43. Joseph EK, Green PG, Bogen O, Alvarez P, Levine JD. Vascular endothelial cells mediate mechanical stimulation-induced enhancement of endothelin hyperalgesia via activation of P2X2/3 receptors on nociceptors. J Neurosci. 2013 ; 33: 2849-59
44. Kaan TK, Yip PK, Patel S, Davies M, Marchand F, Cockayne DA. Systemic blockade of P2X3 and P2X2/3 receptors attenuates bone cancer pain behaviour in rats. Brain. 2010 ; 133: 2549-64
45. Karai L, Brown DC, Mannes AJ, Connelly ST, Brown J, Gandal M. 2004. Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control. J Clin Invest. 2004 ; 113: 1344-52
46. Kehl LJ, Hamamoto DT, Wacnik PW, Croft DL, Norsted BD, Wilcox GL. A cannabinoid agonist differentially attenuates deep tissue hyperalgesia in animal models of cancer and inflammatory muscle pain. Pain. 2003 ; 103: 175-86
47. Khasabov SG, Hamamoto DT, Harding-Rose C, Simone DA. Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain. Brain Res. 2007 ; 1180: 7-19
48. Khasabova IA, Chandiramani A, Harding-Rose C, Simone DA, Seybold VS. Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain. Pharmacol Res. 2011a ; 64: 60-7
49. Khasabova IA, Gielissen J, Chandiramani A, Harding-Rose C, Odeh DA, Simone DA. CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain. Behav Pharmacol. 2011b ; 22: 607-16
50. Khasabova IA, Holman M, Morse T, Burlakova N, Coicou L, Harding-Rose C. Increased anandamide uptake by sensory neurons contributes to hyperalgesia in a model of cancer pain. Neurobiol Dis. 2013 ; 58C: 19-28
51. Khasabova IA, Khasabov SG, Harding-Rose C, Coicou LG, Seybold BA, Lindberg AE. A decrease in anandamide signaling contributes to the maintenance of cutaneous mechanical hyperalgesia in a model of bone cancer pain. J Neurosci. 2008 ; 28: 11141-52
52. Khasabova IA, Stucky CL, Harding-Rose C, Eikmeier L, Beitz AJ, Coicou LG. Chemical interactions between fibrosarcoma cancer cells and sensory neurons contribute to cancer pain. J Neurosci. 2007 ; 27: 10289-98
53. Kim WM, Jeong CW, Lee SH, Kim YO, Cui JH, Yoon MH. The intrathecally administered kappa-2 opioid agonist GR89696 and interleukin-10 attenuate bone cancer-induced pain through synergistic interaction. Anesth Analg. 2011 ; 113: 934-40
54. King TE, Pawar SC, Majuta L, Sroka IC, Wynn D, Demetriou MC. The role of alpha 6 integrin in prostate cancer migration and bone pain in a novel xenograft model. PLoS One. 2008 ; 3: e3535
55. Kuraishi Y, Iida Y, Zhang HW, Uehara S, Nojima H, Murata J. Suppression by gabapentin of pain-related mechano-responses in mice given orthotopic tumor inoculation. Biol Pharm Bull. 2003 ; 26: 550-2
56. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 ; 363: 1693-703
57. Lam DK, Dang D, Zhang J, Dolan JC, Schmidt BL.. Novel animal models of acute and chronic cancer pain: a pivotal role for PAR2. J Neurosci. 2012 2012 ; 32: 14178-83
58. Lam DK, Schmidt BL. Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway. Pain. 2010 ; 149: 263-72
59. Lan LS, Ping YJ, Na WL, Miao J, Cheng QQ, Ni MZ. Down-regulation of Toll-like receptor 4 gene expression by short interfering RNA attenuates bone cancer pain in a rat model. Mol Pain. 2010 ; 6: 2
60. Lautner MA, Ruparel SB, Patil MJ, Hargreaves KM. In vitro sarcoma cells release a lipophilic substance that activates the pain transduction system via TRPV1. Ann Surg Oncol. 2011 ; 18: 866-71
61. Li X, Wang XW, Feng XM, Zhou WJ, Wang YQ, Mao-Ying QL. Stage-dependent anti-allodynic effects of intrathecal Toll-like receptor 4 antagonists in a rat model of cancer induced bone pain. J Physiol Sci. 2013 ; 63: 203-9
62. Lihua P, Su M, Zejun Z, Ke W, Bennett MI. Spinal cord stimulation for cancer-related pain in adults. Cochrane Database Syst Rev. 2013 ; 2: CD009389
63. Liu J, Liu FY, Tong ZQ, Li ZH, Chen W, Luo WH. Lysine-specific demethylase 1 in breast cancer cells contributes to the production of endogenous formaldehyde in the metastatic bone cancer pain model of rats. PLoS One. 2013 ; 8: e58957
64. Liu S, Liu WT, Liu YP, Dong HL, Henkemeyer M, Xiong LZ. Blocking EphB1 receptor forward signaling in spinal cord relieves bone cancer pain and rescues analgesic effect of morphine treatment in rodents. Cancer Res. 2011 ; 71: 4392-402
65. Lozano-Ondoua AN, Wright C, Vardanyan A, King T, Largent-Milnes TM, Nelson M. A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. Life Sci. 2010 ; 86: 646-53
66. Magnon C, Hall SJ, Lin J, Xue X, Gerber L, Freedland SJ. Autonomic nerve development contributes to prostate cancer progression. Science. 2013 ; 341: 1236361
67. Mantyh WG, Jimenez-Andrade JM, Stake JI, Bloom AP, Kaczmarska MJ, Taylor RN. Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain. Neuroscience. 2010 ; 171: 588-98
68. Mapp PI, Walsh DA. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol. 2012 ; 8: 390-8
69. Mayordomo C, Garcia-Recio S, Ametller E, Fernandez-Nogueira P, Pastor-Arroyo EM, Vinyals L. Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2. J Cell Physiol. 2012 ; 227: 1358-66
70. Mercadante S, Giarratano A.. The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: a critical review. Crit Rev Oncol Hematol. 2013 ; 87: 140-5
71. Nagae M, Hiraga T, Yoneda T.. Acidic microenvironment created by osteoclasts causes bone pain associated with tumor colonization. J Bone Miner Metab. 2007 ; 25: 99-104
72. Nagamine K, Ozaki N, Shinoda M, Asai H, Nishiguchi H, Mitsudo K. Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats. J Pain. 2006 ; 7: 659-70
73. Neumann E. Secondare cancroid infiltration des nervus mentalis bei einem. Arch Pathol Anat. 1862 ; 24: 201
74. Nico B, Mangieri D, Benagiano V, Crivellato E, Ribatti D.. Nerve growth factor as an angiogenic factor. Microvasc Res. 2008 ; 75: 135-41
75. 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: 251-8
76. Ono K, Harano N, Nagahata S, Seta Y, Tsujisawa T, Inenaga K. Behavioral characteristics and c-Fos expression in the medullary dorsal horn in a rat model for orofacial cancer pain. Eur J Pain. 2009 ; 13: 373-9
77. Paley CA, Johnson MI, Tashani OA, Bagnall AM.. Acupuncture for cancer pain in adults. Cochrane Database Syst Rev. 2011 ; (1). CD007753
78. Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012 ; 13: 438-49
79. Potenzieri C, Harding-Rose C, Simone DA. The cannabinoid receptor agonist, WIN 55, 212-2, attenuates tumor-evoked hyperalgesia through peripheral mechanisms. Brain Res. 2008 ; 1215: 69-75
80. Qiu F, Jiang Y, Zhang H, Liu Y, Mi W.. Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain. Neurosci Lett. 2012 ; 512: 61-6
81. Radtke C, Vogt PM, Devor M, Kocsis JD. Keratinocytes acting on injured afferents induce extreme neuronal hyperexcitability and chronic pain. Pain. 2010 ; 148: 94-102
82. Rakvag TT, Ross JR, Sato H, Skorpen F, Kaasa S, Klepstad P.. Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol Pain. 2008 ; 4: 64
83. Ren BX, Gu XP, Zheng YG, Liu CL, Wang D, Sun YE. Intrathecal injection of metabotropic glutamate receptor subtype 3 and 5 agonist/antagonist attenuates bone cancer pain by inhibition of spinal astrocyte activation in a mouse model. Anesthesiology. 2012 ; 116: 122-32
84. Sabino MA, Ghilardi JR, Jongen JL, Keyser CP, Luger NM, Mach DB. Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2. Cancer Res. 2002 ; 62: 7343-9
85. Sabino MA, Luger NM, Mach DB, Rogers SD, Schwei MJ, Mantyh PW. Different tumors in bone each give rise to a distinct pattern of skeletal destruction, bone cancer-related pain behaviors and neurochemical changes in the central nervous system. Int J Cancer. 2003 ; 104: 550-8
86. Saghafi N, Lam DK, Schmidt BL. Cannabinoids attenuate cancer pain and proliferation in a mouse model. Neurosci Lett. 2011 ; 488: 247-51
87. Sago T, Ono K, Harano N, Furuta-Hidaka K, Hitomi S, Nunomaki M. Distinct time courses of microglial and astrocytic hyperactivation and the glial contribution to pain hypersensitivity in a facial cancer model. Brain Res. 2012 ; 1457: 70-80
88. Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML. Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci. 1999 ; 19: 10886-97
89. Sevcik MA, Ghilardi JR, Halvorson KG, Lindsay TH, Kubota K, Mantyh PW. Analgesic efficacy of bradykinin B1 antagonists in a murine bone cancer pain model. J Pain. 2005 ; 6: 771-5
90. Sevcik MA, Ghilardi JR, Peters CM, Lindsay TH, Halvorson KG, Jonas BM. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain. 2005 ; 115: 128-41
91. Shimoyama M, Tanaka K, Hasue F, Shimoyama N.. A mouse model of neuropathic cancer pain. Pain. 2002 ; 99: 167-74
92. Shimoyama M, Tatsuoka H, Ohtori S, Tanaka K, Shimoyama N.. Change of dorsal horn neurochemistry in a mouse model of neuropathic cancer pain. Pain. 2005 ; 114: 221-30
93. Shinoda M, Ogino A, Ozaki N, Urano H, Hironaka K, Yasui M. Involvement of TRPV1 in nociceptive behavior in a rat model of cancer pain. J Pain. 2008 ; 9: 687-99
94. Smeester BA, Al-Gizawiy M, Beitz AJ. Effects of different electroacupuncture scheduling regimens on murine bone tumor-induced hyperalgesia: sex differences and role of inflammation. Evid Based Complement Alternat Med. 2012 ; 2012: 671386
95. Stock K, Kumar J, Synowitz M, Petrosino S, Imperatore R, Smith ES. Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1. Nat Med. 2012 ; 18: 1232-8
96. Suzuki M, Narita M, Hasegawa M, Furuta S, Kawamata T, Ashikawa M. Sensation of abdominal pain induced by peritoneal carcinomatosis is accompanied by changes in the expression of substance P and mu-opioid receptors in the spinal cord of mice. Anesthesiology. 2012 ; 117: 847-56
97. Szabo T, Olah Z, Iadarola MJ, Blumberg PM. Epidural resiniferatoxin induced prolonged regional analgesia to pain. Brain Res. 1999 ; 840: 92-8
98. Tong W, Wang W, Huang J, Ren N, Wu SX, Li YQ. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain. Biochem Biophys Res Commun. 2010 ; 395: 572-6
99. Urch CE, Donovan-Rodriguez T, Dickenson AH. Alterations in dorsal horn neurones in a rat model of cancer-induced bone pain. Pain. 2003 ; 106: 347-56
100. Urch CE, Donovan-Rodriguez T, Gordon-Williams R, Bee LA, Dickenson AH. Efficacy of chronic morphine in a rat model of cancer-induced bone pain: behavior and in dorsal horn pathophysiology. J Pain. 2005 ; 6: 837-45
101. Vachon P, Millecamps M, Low L, Thompsosn SJ, Pailleux F, Beaudry F. Alleviation of chronic neuropathic pain by environmental enrichment in mice well after the establishment of chronic pain. Behav Brain Funct sssssssss. 2013 ; 9: 22
102. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J.. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007 ; 18: 1437-49
103. Vanhecke E, Adriaenssens E, Verbeke S, Meignan S, Germain E, Berteaux N. Brain-derived neurotrophic factor and neurotrophin-4/5 are expressed in breast cancer and can be targeted to inhibit tumor cell survival. Clin Cancer Res. 2011 ; 17: 1741-52
104. Vit JP, Ohara PT, Tien DA, Fike JR, Eikmeier L, Beitz A. The analgesic effect of low dose focal irradiation in a mouse model of bone cancer is associated with spinal changes in neuro-mediators of nociception. Pain. 2006 ; 120: 188-201
105. Wacnik PW, Baker CM, Herron MJ, Kren BT, Blazar BR, Wilcox GL. Tumor-induced mechanical hyperalgesia involves CGRP receptors and altered innervation and vascularization of DsRed2 fluorescent hindpaw tumors. Pain. 2005 ; 115: 95-106
106. Wacnik PW, Eikmeier LJ, Ruggles TR, Ramnaraine ML, Walcheck BK, Beitz AJ. Functional interactions between tumor and peripheral nerve: morphology, algogen identification, and behavioral characterization of a new murine model of cancer pain. J Neurosci. 2001 ; 21: 9355-66
107. Wacnik PW, Kehl LJ, Trempe TM, Ramnaraine ML, Beitz AJ, Wilcox GL. Tumor implantation in mouse humerus evokes movement-related hyperalgesia exceeding that evoked by intramuscular carrageenan. Pain. 2003 ; 101: 175-86
108. Wang XW, Hu S, Mao-Ying QL, Li Q, Yang CJ, Zhang H. Activation of c-jun N-terminal kinase in spinal cord contributes to breast cancer induced bone pain in rats. Mol Brain. 2012a ; 5: 21
109. Wang XW, Li TT, Zhao J, Mao-Ying QL, Zhang H, Hu S. Extracellular signal-regulated kinase activation in spinal astrocytes and microglia contributes to cancer-induced bone pain in rats. Neuroscience. 2012b ; 217: 172-81
110. Wu JX, Xu MY, Miao XR, Lu ZJ, Yuan XM, Li XQ. Functional up-regulation of P2X3 receptors in dorsal root ganglion in a rat model of bone cancer pain. Eur J Pain. 2012 ; 16: 1378-88
111. Yamamoto J, Kawamata T, Niiyama Y, Omote K, Namiki A.. Down-regulation of mu opioid receptor expression within distinct subpopulations of dorsal root ganglion neurons in a murine model of bone cancer pain. Neuroscience. 2008 ; 151: 843-53
112. Yanagisawa Y, Furue H, Kawamata T, Uta D, Yamamoto J, Furuse S. Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord. Mol Pain. 2010 ; 6: 38
113. Yao M, Chang XY, Chu YX, Yang JP, Wang LN, Cao HQ. Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain. J Neurosci Res. 2011 ; 89: 1877-86
114. Ye Y, Dang D, Viet CT, Dolan JC, Schmidt BL. Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. J Pain. 2012 ; 13: 524-31
115. Ye Y, Dang D, Zhang J, Viet CT, Lam DK, Dolan JC. Nerve growth factor links oral cancer progression, pain, and cachexia. Mol Cancer Ther. 2011 ; 10: 1667-76
116. Yin Q, Cheng W, Cheng MY, Fan SZ, Shen W.. Intrathecal injection of anti-CX3CR1 neutralizing antibody delayed and attenuated pain facilitation in rat tibial bone cancer pain model. Behav Pharmacol. 2010 ; 21: 595-601
117. Zeppetella G, Davies AN. Opioids for the management of breakthrough pain in cancer patients. Cochrane Database Syst Rev. 2013 ; 10:
118. Zhang RX, Li A, Liu B, Wang L, Ren K, Qiao JT. Electroacupuncture attenuates bone cancer pain and inhibits spinal interleukin-1-β expression in a rat model. Anesth Analg. 2007 ; 105: 1482-8
119. Zhang RX, Li A, Liu B, Wang L, Xin J, Ren K. Electroacupuncture attenuates bone-cancer-induced hyperalgesia and inhibits spinal preprodynorphin expression in a rat model. Eur J Pain. 2008 ; 12: 870-8
120. Zhang RX, Liu B, Wang L, Ren K, Qiao JT, Berman BM. Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia. Pain. 2005 ; 118: 125-36
121. Zhang YK, Huang ZJ, Liu S, Liu YP, Song AA, Song XJ. WNT signaling underlies the pathogenesis of neuropathic pain in rodents. J Clin Invest. 2013 ; 123: 2268-86