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New insights of nociceptor sensitization in bone cancer pain

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Bibliography

  • Sabino MA, Mantyh PW. Pathophysiology of bone cancer pain. J Support Oncol 2005;3(1):15-24
  • Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12(20 Pt 2):6243s-9s
  • Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69(1-2):1-18
  • McQuay HJ, Collins SL, Carroll D, et al. Radiotherapy for the palliation of painful bone metastases. Cochrane Database Syst Rev 2000(2):CD001793
  • Dy SM, Asch SM, Naeim A, et al. Evidence-based standards for cancer pain management. J Clin Oncol 2008;26(23):3879-85
  • Casuccio A, Mercadante S, Fulfaro F. Treatment strategies for cancer patients with breakthrough pain. Expert Opin Pharmacother 2009;10(6):947-53
  • Mercadante S, Villari P, Ferrera P, et al. Optimization of opioid therapy for preventing incident pain associated with bone metastases. J Pain Symptom Manage 2004;28(5):505-10
  • Skeletal Complications of Malignancy. Proceedings of a symposium. Bethesda, Maryland, April 19-20, 1997. Cancer 1997;80(8 Suppl):1527-701
  • Merskey H, Bogduk N. Classification of chronic pain. IASP; Seattle; 1994
  • Hamamoto DT, Khasabov SG, Cain DM, et al. Tumor-evoked sensitization of C nociceptors: a role for endothelin. J Neurophysiol 2008;100(4):2300-11
  • Murdaca G, Colombo BM, Puppo F. Anti-TNF-alpha inhibitors: a new therapeutic approach for inflammatory immune-mediated diseases: an update upon efficacy and adverse events. Int J Immunopathol Pharmacol 2009;22(3):557-65
  • Bharucha AE, Linden DR. Linaclotide - a secretagogue and antihyperalgesic agent - what next? Neurogastroenterol Motil 2010;22(3):227-31
  • Edvinsson L, Ho TW. CGRP receptor antagonism and migraine. Neurotherapeutics 2010;7(2):164-75
  • Davidson B, Lazarovici P, Ezersky A, et al. Expression levels of the nerve growth factor receptors TrkA and p75 in effusions and solid tumors of serous ovarian carcinoma patients. Clin Cancer Res 2001;7(11):3457-64
  • Piomelli D, Sasso O. Peripheral gating of pain signals by endogenous lipid mediators. Nat Neurosci 2014;17(2):164-74
  • Snider McMahon SB. Tackling pain at the source: new ideas about nociceptors. Neuron 1998;20:629-32
  • Elitt CM, McIlwrath SL, Lawson JJ, et al. Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold. J Neurosci 2006;26(33):8578-87
  • Gold MS, Gebhart GF. Nociceptor sensitization in pain pathogenesis. Nat Med 2010;16(11):1248-57
  • Lynn B, Carpenter SE. Primary afferent units from the hairy skin of the rat hind limb. Brain Res 1982;238(1):29-43
  • Castaneda-Corral G, Jimenez-Andrade JM, Bloom AP, et al. The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience 2011;178:196-207
  • Julius D BA. Molecular mechanism of nociception. Nature 2001;413:203-10
  • Yoneda T, Hata K, Nakanishi M, et al. Involvement of acidic microenvironment in the pathophysiology of cancer-associated bone pain. Bone 2011;48(1):100-5
  • Hunt SP, Mantyh PW. The molecular dynamics of pain control. Nat Rev Neurosci 2001;2(2):83-91
  • Zylka MJ, Rice FL, Anderson DJ. Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron 2005;45(1):17-25
  • Jimenez-Andrade JM, Bloom AP, Stake JI, et al. Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain. J Neurosci 2010;30(44):14649-56
  • Djouhri L, Lawson SN. Changes in somatic action potential shape in guinea-pig nociceptive primary afferent neurones during inflammation in vivo. J Physiol 1999;520 Pt 2:565-76
  • Peng YB, Ringkamp M, Campbell JN, et al. Electrophysiological assessment of the cutaneous arborization of Adelta-fiber nociceptors. J Neurophysiol 1999;82(3):1164-77
  • Aoki Y, Ohtori S, Takahashi K, et al. Expression and co-expression of VR1, CGRP, and IB4-binding glycoprotein in dorsal root ganglion neurons in rats: differences between the disc afferents and the cutaneous afferents. Spine (Phila Pa 1976) 2005;30(13):1496-500
  • Jimenez-Andrade JM, Mantyh WG, Bloom AP, et al. A phenotypically restricted set of primary afferent nerve fibers innervate the bone versus skin: therapeutic opportunity for treating skeletal pain. Bone 2010;46(2):306-13
  • Zhao J, Pan HL, Li TT, et al. The sensitization of peripheral C-fibers to lysophosphatidic acid in bone cancer pain. Life Sci 2010;87(3-4):120-5
  • Zhang JM, Donnelly DF, Song XJ, et al. Axotomy increases the excitability of dorsal root ganglion cells with unmyelinated axons. J Neurophysiol 1997;78(5):2790-4
  • Abdulla FA, Smith PA. Axotomy- and autotomy-induced changes in the excitability of rat dorsal root ganglion neurons. J Neurophysiol 2001;85(2):630-43
  • Walters ET. Injury-related behavior and neuronal plasticity: an evolutionary perspective on sensitization, hyperalgesia, and analgesia. Int Rev Neurobiol 1994;36:325-427
  • Chung JM, Chung K. Importance of hyperexcitability of DRG neurons in neuropathic pain. Pain Pract 2002;2(2):87-97
  • Kim YI, Na HS, Kim SH, et al. Cell type-specific changes of the membrane properties of peripherally-axotomized dorsal root ganglion neurons in a rat model of neuropathic pain. Neuroscience 1998;86(1):301-9
  • Ma C, Shu Y, Zheng Z, et al. Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons. J Neurophysiol 2003;89(3):1588-602
  • Djouhri L, Dawbarn D, Robertson A, et al. Time course and nerve growth factor dependence of inflammation-induced alterations in electrophysiological membrane properties in nociceptive primary afferent neurons. J Neurosci 2001;21(22):8722-33
  • Xu GY, Winston JH, Shenoy M, et al. Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis. Am J Physiol Gastrointest Liver Physiol 2006;291(3):G424-31
  • Djouhri L, Lawson SN. Increased conduction velocity of nociceptive primary afferent neurons during unilateral hindlimb inflammation in the anaesthetised guinea-pig. Neuroscience 2001;102(3):669-79
  • Djouhri L, Koutsikou S, Fang X, et al. Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J Neurosci 2006;26(4):1281-92
  • Maingret F, Coste B, Padilla F, et al. Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. J Gen Physiol 2008;131(3):211-25
  • Ma C, Greenquist KW, Lamotte RH. Inflammatory mediators enhance the excitability of chronically compressed dorsal root ganglion neurons. J Neurophysiol 2006;95(4):2098-107
  • Cain DM, Wacnik PW, Turner M, et al. 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(23):9367-76
  • Wacnik PW, Eikmeier LJ, Ruggles TR, et al. 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(23):9355-66
  • 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(1-3):73-87
  • Khasabov SG, Hamamoto DT, Harding-Rose C, et al. Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain. Brain Res 2007;1180:7-19
  • Peters CM, Ghilardi JR, Keyser CP, et al. Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain. Exp Neurol 2005;193(1):85-100
  • Zheng Q, Fang D, Cai J, et al. Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain. Mol Pain 2012;8:24
  • Ritter AM, Mendell LM. Somal membrane properties of physiologically identified sensory neurons in the rat: effects of nerve growth factor. J Neurophysiol 1992;68(6):2033-41
  • Kirchhoff C, Leah JD, Jung S, et al. Excitation of cutaneous sensory nerve endings in the rat by 4-aminopyridine and tetraethylammonium. J Neurophysiol 1992;67(1):125-31
  • Baumann TK, Chaudhary P, Martenson ME. Background potassium channel block and TRPV1 activation contribute to proton depolarization of sensory neurons from humans with neuropathic pain. Eur J Neurosci 2004;19(5):1343-51
  • Mantyh PW. Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci 2006;7(10):797-809
  • Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009;9(4):239-52
  • Woodbury CJ, Zwick M, Wang S, et al. Nociceptors lacking TRPV1 and TRPV2 have normal heat responses. J Neurosci 2004;24(28):6410-15
  • Stockbridge N. Differential conduction at axonal bifurcations. II. Theoretical basis. J Neurophysiol 1988;59(4):1286-95
  • Lozano-Ondoua AN, Symons-Liguori AM, Vanderah TW. Cancer-induced bone pain: mechanisms and models. Neurosci Lett 2013;557 Pt A:52-9
  • Mantyh P. Bone cancer pain: causes, consequences, and therapeutic opportunities. Pain 2013;154(Suppl 1):S54-62
  • Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997;389(6653):816-24
  • Tominaga M, Caterina MJ, Malmberg AB, et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998;21(3):531-43
  • Swanson DM, Dubin AE, Shah C, et al. Identification and biological evaluation of 4-(3-trifluoromethylpyridin-2-yl)piperazine-1-carboxylic acid (5-trifluoromethylpyridin-2-yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist. J Med Chem 2005;48(6):1857-72
  • Lautner MA, Ruparel SB, Patil MJ, et al. In vitro sarcoma cells release a lipophilic substance that activates the pain transduction system via TRPV1. Ann Surg Oncol 2011;18(3):866-71
  • Honore P, Rogers SD, Schwei MJ, et al. 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(3):585-98
  • Clohisy DR, Mantyh PW. Bone cancer pain. Clin Orthop Relat Res 2003(415 Suppl):S279-88
  • Ghilardi JR, Rohrich H, Lindsay TH, et al. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci 2005;25(12):3126-31
  • Means AR. Regulatory cascades involving calmodulin-dependent protein kinases. Mol Endocrinol 2000;14(1):4-13
  • Mellstrom B, Savignac M, Gomez-Villafuertes R, et al. Ca2+-operated transcriptional networks: molecular mechanisms and in vivo models. Physiol Rev 2008;88(2):421-49
  • Nakanishi M, Hata K, Nagayama T, 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
  • Li Y, Cai J, Han Y, 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
  • Deval E, Gasull X, Noel J, et al. Acid-sensing ion channels (ASICs): pharmacology and implication in pain. Pharmacol Ther 2010;128(3):549-58
  • Voilley N, de Weille J, Mamet J, et al. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci 2001;21(20):8026-33
  • Reeh PW, Kress M. Molecular physiology of proton transduction in nociceptors. Curr Opin Pharmacol 2001;1(1):45-51
  • Olson TH, Riedl MS, Vulchanova L, et al. An acid sensing ion channel (ASIC) localizes to small primary afferent neurons in rats. Neuroreport 1998;9(6):1109-13
  • 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
  • Qiu F, Wei X, Zhang S, et al. 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
  • Leo S, D’Hooge R, Meert T. Exploring the role of nociceptor-specific sodium channels in pain transmission using Nav1.8 and Nav1.9 knockout mice. Behav Brain Res 2010;208(1):149-57
  • Joshi SK, Mikusa JP, Hernandez G, et al. Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states. Pain 2006;123(1-2):75-82
  • Joshi SK, Honore P, Hernandez G, et al. Additive antinociceptive effects of the selective Nav1.8 blocker A-803467 and selective TRPV1 antagonists in rat inflammatory and neuropathic pain models. J Pain 2009;10(3):306-15
  • Miao XR, Gao XF, Wu JX, et al. Bilateral downregulation of Nav1.8 in dorsal root ganglia of rats with bone cancer pain induced by inoculation with Walker 256 breast tumor cells. BMC Cancer 2010;10:216
  • Qiu F, Jiang Y, Zhang H, et al. 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(2):61-6
  • Bao Y, Hua B, Hou W, et al. Involvement of protease-activated receptor 2 in nociceptive behavior in a rat model of bone cancer. J Mol Neurosci 2014;52(4):566-76
  • Bao Y, Hou W, Hua B. Protease-activated receptor 2 signalling pathways: a role in pain processing. Expert Opin Ther Targets 2014;18(1):15-27
  • Brown DA, Passmore GM. Neural KCNQ (Kv7) channels. Br J Pharmacol 2009;156(8):1185-95
  • Wulff H, Castle NA, Pardo LA. Voltage-gated potassium channels as therapeutic targets. Nat Rev Drug Discov 2009;8(12):982-1001
  • Zheng Q, Fang D, Liu M, et al. Suppression of KCNQ/M (Kv7) potassium channels in dorsal root ganglion neurons contributes to the development of bone cancer pain in a rat model. Pain 2013;154(3):434-48
  • Garcia-Villegas R, Lopez-Alvarez LE, Arni S, et al. Identification and functional characterization of the promoter of the mouse sodium-activated sodium channel Na(x) gene (Scn7a). J Neurosci Res 2009;87(11):2509-19
  • Widmark J, Sundstrom G, Ocampo Daza D, et al. Differential evolution of voltage-gated sodium channels in tetrapods and teleost fishes. Mol Biol Evol 2011;28(1):859-71
  • Goldin AL, Barchi RL, Caldwell JH, et al. Nomenclature of voltage-gated sodium channels. Neuron 2000;28(2):365-8
  • Yu FH, Catterall WA. Overview of the voltage-gated sodium channel family. Genome Biol 2003;4(3):207
  • Hiyama TY, Watanabe E, Ono K, et al. Na(x) channel involved in CNS sodium-level sensing. Nat Neurosci 2002;5(6):511-12
  • Shimizu H, Watanabe E, Hiyama TY, et al. Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. Neuron 2007;54(1):59-72
  • Watanabe E, Fujikawa A, Matsunaga H, et al. Nav2/NaG channel is involved in control of salt-intake behavior in the CNS. J Neurosci 2000;20(20):7743-51
  • Hiyama TY, Watanabe E, Okado H, et al. The subfornical organ is the primary locus of sodium-level sensing by Na(x) sodium channels for the control of salt-intake behavior. J Neurosci 2004;24(42):9276-81
  • Hiyama TY, Matsuda S, Fujikawa A, et al. Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia. Neuron 2010;66(4):508-22
  • Grob M, Drolet G, Mouginot D. Specific Na+ sensors are functionally expressed in a neuronal population of the median preoptic nucleus of the rat. J Neurosci 2004;24(16):3974-84
  • Gorter JA, Zurolo E, Iyer A, et al. Induction of sodium channel Na(x) (SCN7A) expression in rat and human hippocampus in temporal lobe epilepsy. Epilepsia 2010;51(9):1791-800
  • Ke CB, He WS, Li CJ, et al. Enhanced SCN7A/Nax expression contributes to bone cancer pain by increasing excitability of neurons in dorsal root ganglion. Neuroscience 2012;227:80-9
  • Gilchrist LS, Cain DM, Harding-Rose C, et al. Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain. Brain Res 2005;1044(2):197-205
  • Nagamine K, Ozaki N, Shinoda M, et al. Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats. J Pain 2006;7(9):659-70
  • Gonzalez-Rodriguez S, Pevida M, Roques BP, et al. Involvement of enkephalins in the inhibition of osteosarcoma-induced thermal hyperalgesia evoked by the blockade of peripheral P2X3 receptors. Neurosci Lett 2009;465(3):285-9
  • Kaan TK, Yip PK, Patel S, et al. Systemic blockade of P2X3 and P2X2/3 receptors attenuates bone cancer pain behaviour in rats. Brain 2010;133(9):2549-64
  • Wu JX, Xu MY, Miao XR, et al. Functional up-regulation of P2X3 receptors in dorsal root ganglion in a rat model of bone cancer pain. Eur J Pain 2012;16(10):1378-88
  • Vergnolle N, Bunnett NW, Sharkey KA, et al. Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat Med 2001;7(7):821-6
  • Alier KA, Endicott JA, Stemkowski PL, et al. Intrathecal administration of proteinase-activated receptor-2 agonists produces hyperalgesia by exciting the cell bodies of primary sensory neurons. J Pharmacol Exp Ther 2008;324(1):224-33
  • Bao Y, Hou W, Hua B. Protease-activated receptor 2 signalling pathways: a role in pain processing. Expert Opin Ther Targets 2014;18(1):15-27
  • Lam DK, Schmidt BL. Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway. Pain 2010;149(2):263-72
  • Lam DK, Dang D, Zhang J, et al. Novel animal models of acute and chronic cancer pain: a pivotal role for PAR2. J Neurosci 2012;32(41):14178-83
  • Liu S, Liu YP, Yue DM, et al. Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain. Eur J Pain 2014;18(3):326-37
  • Bao Y, Hou W, Liu R, et al. PAR2-mediated upregulation of BDNF contributes to central sensitization in bone cancer pain. Mol Pain 2014;10:28
  • Amadesi S, Cottrell GS, Divino L, et al. Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice. J Physiol 2006;575(Pt 2):555-71
  • Dai Y, Wang S, Tominaga M, et al. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest 2007;117(7):1979-87
  • Grant AD, Cottrell GS, Amadesi S, et al. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol 2007;578(Pt 3):715-33
  • Chen Y, Yang C, Wang ZJ. Proteinase-activated receptor 2 sensitizes transient receptor potential vanilloid 1, transient receptor potential vanilloid 4, and transient receptor potential ankyrin 1 in paclitaxel-induced neuropathic pain. Neuroscience 2011;193:440-51
  • Gokin AP, Fareed MU, Pan HL, et al. Local injection of endothelin-1 produces pain-like behavior and excitation of nociceptors in rats. J Neurosci 2001;21(14):5358-66
  • Khodorova A, Navarro B, Jouaville LS, et al. Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nat Med 2003;9(8):1055-61
  • Hans G, Deseure K, Robert D, et al. Neurosensory changes in a human model of endothelin-1 induced pain: a behavioral study. Neurosci Lett 2007;418(2):117-21
  • Davar G. Endothelin-1 and metastatic cancer pain. Pain Med 2001;2(1):24-7
  • Pickering V, Jay Gupta R, Quang P, et al. Effect of peripheral endothelin-1 concentration on carcinoma-induced pain in mice. Eur J Pain 2008;12(3):293-300
  • Pomonis JD, Rogers SD, Peters CM, et al. Expression and localization of endothelin receptors: implications for the involvement of peripheral glia in nociception. J Neurosci 2001;21(3):999-1006
  • Peters CM, Lindsay TH, Pomonis JD, et al. Endothelin and the tumorigenic component of bone cancer pain. Neuroscience 2004;126(4):1043-52
  • Wintzen M, Yaar M, Burbach JP, et al. Proopiomelanocortin gene product regulation in keratinocytes. J Invest Dermatol 1996;106(4):673-8
  • Zanello SB, Jackson DM, Holick MF. An immunocytochemical approach to the study of beta-endorphin production in human keratinocytes using confocal microscopy. Ann N Y Acad Sci 1999;885:85-99
  • Wintzen M, Zanello SB, Holick MF, et al. Condition-dependent presence of beta-lipotropin-like peptide in human keratinocytes. Peptides 2000;21(5):691-7
  • Couture R, Harrisson M, Vianna RM, et al. Kinin receptors in pain and inflammation. Eur J Pharmacol 2001;429(1-3):161-76
  • Fox A, Wotherspoon G, McNair K, et al. Regulation and function of spinal and peripheral neuronal B1 bradykinin receptors in inflammatory mechanical hyperalgesia. Pain 2003;104(3):683-91
  • Sevcik MA, Ghilardi JR, Halvorson KG, et al. Analgesic efficacy of bradykinin B1 antagonists in a murine bone cancer pain model. J Pain 2005;6(11):771-5
  • Southall MD, Michael RL, Vasko MR. Intrathecal NSAIDS attenuate inflammation-induced neuropeptide release from rat spinal cord slices. Pain 1998;78(1):39-48
  • Jimenez-Andrade JM, Ghilardi JR, Castaneda-Corral G, et al. Preventive or late administration of anti-NGF therapy attenuates tumor-induced nerve sprouting, neuroma formation, and cancer pain. Pain 2011;152(11):2564-74
  • Wang W, Chen J, Guo X. The role of nerve growth factor and its receptors in tumorigenesis and cancer pain. Biosci Trends 2014;8(2):68-74
  • Ji RR, Samad TA, Jin SX, et al. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 2002;36(1):57-68
  • Gould HJIII, Gould TN, England JD, et al. A possible role for nerve growth factor in the augmentation of sodium channels in models of chronic pain. Brain Res 2000;854(1-2):19-29
  • Ramer MS, Bradbury EJ, McMahon SB. Nerve growth factor induces P2X(3) expression in sensory neurons. J Neurochem 2001;77(3):864-75
  • Ghilardi JR, Freeman KT, Jimenez-Andrade JM, et al. Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain. Mol Pain 2010;6:87
  • Dallas SL, Rosser JL, Mundy GR, et al. Proteolysis of latent transforming growth factor-beta (TGF-beta) -binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J Biol Chem 2002;277(24):21352-60
  • Xu Q, Zhang XM, Duan KZ, et al. Peripheral TGF-beta1 signaling is a critical event in bone cancer-induced hyperalgesia in rodents. J Neurosci 2013;33(49):19099-111
  • Mercadante S, Arcuri E. Breakthrough pain in cancer patients: pathophysiology and treatment. Cancer Treat Rev 1998;24(6):425-32
  • Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999;81(1-2):129-34
  • 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(1):132-40
  • Janig W, Grossmann L, Gorodetskaya N. Mechano- and thermosensitivity of regenerating cutaneous afferent nerve fibers. Exp Brain Res 2009;196(1):101-14
  • McLachlan EM, Janig W, Devor M, et al. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature 1993;363(6429):543-6
  • Amir R, Argoff CE, Bennett GJ, et al. The role of sodium channels in chronic inflammatory and neuropathic pain. J Pain 2006;7(5 Suppl 3):S1-29
  • Alves DP, Soares AC, Francischi JN, et al. Additive antinociceptive effect of the combination of diazoxide, an activator of ATP-sensitive K+ channels, and sodium nitroprusside and dibutyryl-cGMP. Eur J Pharmacol 2004;489(1-2):59-65
  • Zhuang ZY, Xu H, Clapham DE, et al. Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J Neurosci 2004;24(38):8300-9
  • Zhu W, Oxford GS. Phosphoinositide-3-kinase and mitogen activated protein kinase signaling pathways mediate acute NGF sensitization of TRPV1. Mol Cell Neurosci 2007;34(4):689-700
  • Hu HJ, Gereau RWIV. ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. II. Modulation of neuronal excitability. J Neurophysiol 2003;90(3):1680-8
  • Kawasaki Y, Kohno T, Zhuang ZY, 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
  • Ji RR. Mitogen-activated protein kinases as potential targets for pain killers. Curr Opin Investig Drugs 2004;5(1):71-5
  • Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci 2004;74(21):2643-53
  • Ji RR, Kawasaki Y, Zhuang ZY, et al. Protein kinases as potential targets for the treatment of pathological pain. Handb Exp Pharmacol 2007(177):359-89

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