Protease-activated receptor 2 signalling pathways: a role in pain processing

Bibliography

• Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002;5(Suppl):1062-7
   PubMedGoogle Scholar
• Argoff CE, Albrecht P, Irving G, et al. Multimodal analgesia for chronic pain: rationale and future directions. Pain Med 2009;10(Suppl 2):S53-66
   PubMed Web of Science ®Google Scholar
• Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009;10:895-926
   PubMed Web of Science ®Google Scholar
• Miller RJ, Jung H, Bhangoo SK, et al. Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol 2009(194):417-49
   PubMedGoogle Scholar
• Russell FA, McDougall JJ. Proteinase activated receptor (PAR) involvement in mediating arthritis pain and inflammation. Inflamm Res 2009;58:119-26
   Google Scholar
• Seybold VS. The role of peptides in central sensitization. Handb Exp Pharmacol 2009(194):451-91
   Google Scholar
• Bunnett NW. Protease-activated receptors: how proteases signal to cells to cause inflammation and pain. Semin Thromb Hemost 2006;32(Suppl 1):39-48
   Google Scholar
• Macfarlane SR, Seatter MJ, Kanke T, et al. Proteinase-activated receptors. Pharmacol Rev 2001;53:245-82
   PubMed Web of Science ®Google Scholar
• Dugina TN, Kiseleva EV, Lange MA, et al. Effect of synthetic peptide thrombin receptor agonist encapsulated in microparticles based on lactic and glycolic acid copolymer on healing of experimental skin wounds in mice. Bull Exp Biol Med 2004;138:463-6
   PubMed Web of Science ®Google Scholar
• Donovan FM, Pike CJ, Cotman CW, et al. Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and RhoA activities. J Neurosci 1997;17:5316-26
   PubMed Web of Science ®Google Scholar
• Patwardhan AM, Diogenes A, Berg KA, et al. PAR-2 agonists activate trigeminal nociceptors and induce functional competence in the delta opioid receptor. Pain 2006;125:114-24
   PubMed Web of Science ®Google Scholar
• Steinhoff M, Vergnolle N, Young SH, et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med 2000;6:151-8
   PubMed Web of Science ®Google Scholar
• Ossovskaya VS, Bunnett NW. Protease-activated receptors: contribution to physiology and disease. Physiol Rev 2004;84:579-621
   PubMed Web of Science ®Google Scholar
• Vergnolle N. Clinical relevance of proteinase activated receptors (pars) in the gut. Gut 2005;54:867-74
   PubMed Web of Science ®Google Scholar
• Dulon S, Cande C, Bunnett NW, et al. Proteinase-activated receptor-2 and human lung epithelial cells: disarming by neutrophil serine proteinases. Am J Respir Cell Mol Biol 2003;28:339-46
   PubMedGoogle Scholar
• Dulon S, Leduc D, Cottrell GS, et al. Pseudomonas aeruginosa elastase disables proteinase-activated receptor 2 in respiratory epithelial cells. Am J Respir Cell Mol Biol 2005;32:411-19
   PubMedGoogle Scholar
• Cenac N, Garcia-Villar R, Ferrier L, et al. Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability. J Immunol 2003;170:4296-300
   PubMed Web of Science ®Google Scholar
• Dai Y, Moriyama T, Higashi T, et al. Proteinase-activated receptor 2-mediated potentiation of transient receptor potential vanilloid subfamily 1 activity reveals a mechanism for proteinase-induced inflammatory pain. J Neurosci 2004;24:4293-9
   PubMed Web of Science ®Google Scholar
• Smith-Swintosky VL, Cheo-Isaacs CT, D'Andrea MR, et al. Protease-activated receptor-2 (PAR-2) is present in the rat hippocampus and is associated with neurodegeneration. J Neurochem 1997;69:1890-6
   PubMed Web of Science ®Google Scholar
• D'Andrea MR, Derian CK, Leturcq D, et al. Characterization of protease-activated receptor-2 immunoreactivity in normal human tissues. J Histochem Cytochem 1998;46:157-64
   PubMed Web of Science ®Google Scholar
• Bushell TJ, Plevin R, Cobb S, et al. Characterization of proteinase-activated receptor 2 signalling and expression in rat hippocampal neurons and astrocytes. Neuropharmacology 2006;50:714-25
   Google Scholar
• Corvera CU, Dery O, McConalogue K, et al. Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2. J Physiol 1999;517(Pt 3):741-56
   Google Scholar
• Cuffe JE, Bertog M, Velazquez-Rocha S, et al. Basolateral PAR-2 receptors mediate KCl secretion and inhibition of Na+ absorption in the mouse distal colon. J Physiol 2002;539:209-22
   PubMed Web of Science ®Google Scholar
• Reed DE, Barajas-Lopez C, Cottrell G, et al. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. J Physiol 2003;547:531-42
   PubMedGoogle Scholar
• Vergnolle N, Bunnett NW, Sharkey KA, et al. Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat Med 2001;7:821-6
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Lam DK, Schmidt BL. Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway. Pain 2010;149:263-72
   PubMed Web of Science ®Google Scholar
• Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997;389:816-24
   PubMed Web of Science ®Google Scholar
• Zygmunt PM, Petersson J, Andersson DA, et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 1999;400:452-7
   PubMed Web of Science ®Google Scholar
• Trevisani L, Chiamenti CM, Gaudenzi P, et al. Endoscopic hemostasis in the treatment of bleeding peptic ulcer. Recenti Prog Med 2002;93:498-504
   Google Scholar
• Shu X, Mendell LM. Nerve growth factor acutely sensitizes the response of adult rat sensory neurons to capsaicin. Neurosci Lett 1999;274:159-62
   PubMed Web of Science ®Google Scholar
• Chuang HH, Prescott ED, Kong H, et al. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 2001;411:957-62
   PubMed Web of Science ®Google Scholar
• Tominaga T, Tominaga Y, Ichikawa M. Simultaneous multi-site recordings of neural activity with an inline multi-electrode array and optical measurement in rat hippocampal slices. Pflugers Archiv 2001;443:317-22
   Google Scholar
• Vellani V, Mapplebeck S, Moriondo A, et al. Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J Physiol 2001;534:813-25
   PubMed Web of Science ®Google Scholar
• Hu HJ, Bhave G, Gereau RW. Prostaglandin and protein kinase A-dependent modulation of vanilloid receptor function by metabotropic glutamate receptor 5: potential mechanism for thermal hyperalgesia. J Neurosci 2002;22:7444-52
   PubMed Web of Science ®Google Scholar
• Rathee PK, Distler C, Obreja O, et al. PKA/AKAP/VR-1 module: a common link of Gs-mediated signaling to thermal hyperalgesia. J Neurosci 2002;22:4740-5
   PubMed Web of Science ®Google Scholar
• Mohapatra DP, Nau C. Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway. J Biol Chem 2003;278:50080-90
   PubMed Web of Science ®Google Scholar
• Amadesi S, Nie J, Vergnolle N, et al. Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci 2004;24:4300-12
   PubMed Web of Science ®Google Scholar
• Hoogerwerf WA, Shenoy M, Winston JH, et al. Trypsin mediates nociception via the proteinase-activated receptor 2: a potentially novel role in pancreatic pain. Gastroenterology 2004;127:883-91
   PubMed Web of Science ®Google Scholar
• Liedtke W, Tobin DM, Bargmann CI, et al. Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans. Proc Natl Acad Sci USA 2003;100(Suppl 2):14531-6
   PubMed Web of Science ®Google Scholar
• Liedtke W, Choe Y, Marti-Renom MA, et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 2000;103:525-35
   PubMed Web of Science ®Google Scholar
• Guler AD, Lee H, Iida T, et al. Heat-evoked activation of the ion channel, TRPV4. J Neurosci 2002;22:6408-14
   PubMed Web of Science ®Google Scholar
• Pedersen S, Lambert IH, Thoroed SM, et al. Hypotonic cell swelling induces translocation of the alpha isoform of cytosolic phospholipase A2 but not the gamma isoform in Ehrlich ascites tumor cells. Eur J Biochem 2000;267:5531-9
   PubMedGoogle Scholar
• Watanabe H, Vriens J, Prenen J, et al. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 2003;424:434-8
   PubMed Web of Science ®Google Scholar
• Watanabe H, Davis JB, Smart D, et al. Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem 2002;277:13569-77
   PubMed Web of Science ®Google Scholar
• 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;578:715-33
   PubMed Web of Science ®Google Scholar
• Liedtke W, Friedman JM. Abnormal osmotic regulation in trpv4-/- mice. Proc Natl Acad Sci USA 2003;100:13698-703
   PubMed Web of Science ®Google Scholar
• Suzuki M, Mizuno A, Kodaira K, et al. Impaired pressure sensation in mice lacking TRPV4. J Biol Chem 2003;278:22664-8
   PubMed Web of Science ®Google Scholar
• 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;32:14178-83
   PubMed Web of Science ®Google Scholar
• Story GM, Peier AM, Reeve AJ, et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 2003;112:819-29
   PubMed Web of Science ®Google Scholar
• Kwan KY, Allchorne AJ, Vollrath MA, et al. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 2006;50:277-89
   PubMed Web of Science ®Google Scholar
• Karashima Y, Talavera K, Everaerts W, et al. TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci USA 2009;106:1273-8
   PubMed Web of Science ®Google Scholar
• Jordt SE, Bautista DM, Chuang HH, et al. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 2004;427:260-5
   PubMed Web of Science ®Google Scholar
• Hill K, Schaefer M. TRPA1 is differentially modulated by the amphipathic molecules trinitrophenol and chlorpromazine. J Biol Chem 2007;282:7145-53
   PubMed Web of Science ®Google Scholar
• 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;575:555-71
   PubMed Web of Science ®Google Scholar
• Dai Y, Wang S, Tominaga M, et al. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest 2007;117:1979-87
   PubMed Web of Science ®Google Scholar
• Wang S, Dai Y, Fukuoka T, et al. Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain. Brain 2008;131:1241-51
   PubMed Web of Science ®Google Scholar
• Schmidt M, Dubin AE, Petrus MJ, et al. Nociceptive signals induce trafficking of TRPA1 to the plasma membrane. Neuron 2009;64:498-509
   PubMed Web of Science ®Google Scholar
• Greco S, Muscella A, Elia MG, et al. Mitogenic signalling by B2 bradykinin receptor in epithelial breast cells. J Cell Physiol 2004;201:84-96
   PubMed Web of Science ®Google Scholar
• Cruz CD, Charrua A, Vieira E, et al. Intrathecal delivery of resiniferatoxin (RTX) reduces detrusor overactivity and spinal expression of TRPV1 in spinal cord injured animals. Exp Neurol 2008;214:301-8
   Google Scholar
• Rozengurt E, Rey O, Waldron RT. Protein kinase D signaling. J Biol Chem 2005;280:13205-8
   PubMed Web of Science ®Google Scholar
• Song MJ, Wang YQ, Wu GC. Lipopolysaccharide-induced protein kinase D activation mediated by interleukin-1beta and protein kinase C. Brain Res 2007;1145:19-27
   Google Scholar
• Wang Y, Kedei N, Wang M, et al. Interaction between protein kinase Cmu and the vanilloid receptor type 1. J Biol Chem 2004;279:53674-82
   PubMed Web of Science ®Google Scholar
• Amadesi S, Grant AD, Cottrell GS, et al. Protein kinase D isoforms are expressed in rat and mouse primary sensory neurons and are activated by agonists of protease-activated receptor 2. J Comp Neurol 2009;516:141-56
   Google Scholar
• Brandlin I, Eiseler T, Salowsky R, et al. Protein kinase C(mu) regulation of the JNK pathway is triggered via phosphoinositide-dependent kinase 1 and protein kinase C(epsilon). J Biol Chem 2002;277:45451-7
   PubMed Web of Science ®Google Scholar
• Haworth RS, Roberts NA, Cuello F, et al. Regulation of protein kinase D activity in adult myocardium: novel counter-regulatory roles for protein kinase Cepsilon and protein kinase A. J Mol Cell Cardiol 2007;43:686-95
   Google Scholar
• Mule F, Baffi MC, Falzone M, et al. Signal transduction pathways involved in the mechanical responses to protease-activated receptors in rat colon. J Pharmacol Exp Ther 2002;303:1265-72
   Google Scholar
• Swystun V, Chen L, Factor P, et al. Apical trypsin increases ion transport and resistance by a phospholipase C-dependent rise of Ca2+. Am J Physiol Lung Cell Mol Physiol 2005;288:L820-30
   PubMed Web of Science ®Google Scholar
• Zugaza JL, Waldron RT, Sinnett-Smith J, et al. Bombesin, vasopressin, endothelin, bradykinin, and platelet-derived growth factor rapidly activate protein kinase D through a protein kinase C-dependent signal transduction pathway. J Biol Chem 1997;272:23952-60
   PubMedGoogle Scholar
• Rey O, Yuan J, Rozengurt E. Intracellular redistribution of protein kinase D2 in response to G-protein-coupled receptor agonists. Biochem Biophys Res Commun 2003;302:817-24
   PubMedGoogle Scholar
• Tan M, Xu X, Ohba M, et al. Thrombin rapidly induces protein kinase D phosphorylation, and protein kinase C delta mediates the activation. J Biol Chem 2003;278:2824-8
   Google Scholar
• Yuan J, Rey O, Rozengurt E. Protein kinase D3 activation and phosphorylation by signaling through G alpha q. Biochem Biophys Res Commun 2005;335:270-6
   Google Scholar
• Ji RR, Woolf CJ. Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol Dis 2001;8:1-10
   PubMed Web of Science ®Google Scholar
• 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;36:57-68
   PubMed Web of Science ®Google Scholar
• Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov 2003;2:717-26
   PubMed Web of Science ®Google Scholar
• Jones MK, Wang H, Peskar BM, et al. Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med 1999;5:1418-23
   PubMed Web of Science ®Google Scholar
• Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 2009;27:1675-84
   PubMed Web of Science ®Google Scholar
• Ma W, Quirion R. The ERK/MAPK pathway, as a target for the treatment of neuropathic pain. Expert Opin Ther Targets 2005;9:699-713
   PubMed Web of Science ®Google Scholar
• Ji RR, Gereau RW, Malcangio M, et al. MAP kinase and pain. Brain Res Rev 2009;60:135-48
   PubMed Web of Science ®Google Scholar
• Santulli RJ, Derian CK, Darrow AL, et al. Evidence for the presence of a protease-activated receptor distinct from the thrombin receptor in human keratinocytes. Proc Natl Acad Sci USA 1995;92:9151-5
   PubMed Web of Science ®Google Scholar
• Bohm SK, Kong W, Bromme D, et al. Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J 1996;314(Pt 3):1009-16
   Google Scholar
• Ubl JJ, Vohringer C, Reiser G. Co-existence of two types of [Ca2+]i-inducing protease-activated receptors (PAR-1 and PAR-2) in rat astrocytes and C6 glioma cells. Neuroscience 1998;86:597-609
   PubMed Web of Science ®Google Scholar
• Kong W, McConalogue K, Khitin LM, et al. Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc Natl Acad Sci USA 1997;94:8884-9
   PubMed Web of Science ®Google Scholar
• DeFea KA, Zalevsky J, Thoma MS, et al. Beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol 2000;148:1267-81
   PubMed Web of Science ®Google Scholar
• Cenac N, Coelho AM, Nguyen C, et al. Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2. Am J Pathol 2002;161:1903-15
   PubMed Web of Science ®Google Scholar
• Takasaki I, Andoh T, Nojima H, et al. Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection. J Pharmacol Exp Ther 2001;296:270-5
   Google Scholar
• Palmer ML, Lee SY, Maniak PJ, et al. Protease-activated receptor regulation of Cl- secretion in Calu-3 cells requires prostaglandin release and CFTR activation. Am J Physiol Cell Physiol 2006;290:C1189-98
   Google Scholar
• de Garavilla L, Vergnolle N, Young SH, et al. Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism. Br J Pharmacol 2001;133:975-87
   PubMed Web of Science ®Google Scholar
• Asfaha S, Brussee V, Chapman K, et al. Proteinase-activated receptor-1 agonists attenuate nociception in response to noxious stimuli. Br J Pharmacol 2002;135:1101-6
   PubMed Web of Science ®Google Scholar
• Kawabata A, Kuroda R, Nishida M, et al. Protease-activated receptor-2 (PAR-2) in the pancreas and parotid gland: immunolocalization and involvement of nitric oxide in the evoked amylase secretion. Life Sci 2002;71:2435-46
   PubMed Web of Science ®Google Scholar
• Holzhausen M, Cortelli JR, da Silva VA, et al. Protease-activated receptor-2 (PAR(2)) in human periodontitis. J Dent Res 2010;89:948-53
   Google Scholar
• Holzhausen M, Balejo RD, Lara GM, et al. Nafamostat mesilate, a potent tryptase inhibitor, modulates periodontitis in rats. Clin Oral Investig 2011;15:967-73
   PubMed Web of Science ®Google Scholar
• Kawabata A, Kawao N, Kuroda R, et al. Peripheral PAR-2 triggers thermal hyperalgesia and nociceptive responses in rats. Neuroreport 2001;12:715-19
   PubMedGoogle Scholar
• Hoogerwerf WA, Zou L, Shenoy M, et al. The proteinase-activated receptor 2 is involved in nociception. J Neurosci 2001;21:9036-42
   PubMedGoogle Scholar
• Coelho AM, Vergnolle N, Guiard B, et al. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology 2002;122:1035-47
   PubMed Web of Science ®Google Scholar
• Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999;353:1959-64
   PubMed Web of Science ®Google Scholar
• Ji RR, Strichartz G. Cell signaling and the genesis of neuropathic pain. Sci STKE 2004;2004:reE14
   PubMedGoogle Scholar
• Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006;367:1618-25
   PubMed Web of Science ®Google Scholar
• Wu G, Ringkamp M, Hartke TV, et al. Early onset of spontaneous activity in uninjured C-fiber nociceptors after injury to neighboring nerve fibers. J Neurosci 2001;21:RC140
   PubMed Web of Science ®Google Scholar
• Ma C, Shu Y, Zheng Z, et al. Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons. J Neurophysiol 2003;89:1588-602
   PubMed Web of Science ®Google Scholar
• Huang ZJ, Li HC, Cowan AA, et al. Chronic compression or acute dissociation of dorsal root ganglion induces cAMP-dependent neuronal hyperexcitability through activation of PAR2. Pain 2012;153:1426-37
   Google Scholar
• Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1-18
   PubMed Web of Science ®Google Scholar
• Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999;81:129-34
   PubMed Web of Science ®Google Scholar
• Connelly ST, Schmidt BL. Evaluation of pain in patients with oral squamous cell carcinoma. J Pain 2004;5:505-10
   PubMedGoogle Scholar
• Kolokythas A, Connelly ST, Schmidt BL. Validation of the University of California San Francisco oral cancer pain questionnaire. J Pain 2007;8:950-3
   Google Scholar
• Diener KM. Bisphosphonates for controlling pain from metastatic bone disease. Am J Health Syst Pharm 1996;53:1917-27
   PubMed Web of Science ®Google Scholar
• Fujita T, Matsui M, Takaku K, et al. Size- and invasion-dependent increase in cyclooxygenase 2 levels in human colorectal carcinomas. Cancer Res 1998;58:4823-6
   PubMed Web of Science ®Google Scholar
• Mantyh PW, Clohisy DR, Koltzenburg M, et al. Molecular mechanisms of cancer pain. Nat Rev Cancer 2002;2:201-9
   PubMed Web of Science ®Google Scholar
• Yoshii M, Jikuhara A, Mori S, et al. Mast cell tryptase stimulates DLD-1 carcinoma through prostaglandin- and MAP kinase-dependent manners. J Pharmacol Sci 2005;98:450-8
   PubMed Web of Science ®Google Scholar
• Aromando RF, Perez MA, Heber EM, et al. Potential role of mast cells in hamster cheek pouch carcinogenesis. Oral Oncol 2008;44:1080-7
   Google Scholar
• Noorbakhsh F, Vergnolle N, Hollenberg MD, et al. Proteinase-activated receptors in the nervous system. Nat Rev Neurosci 2003;4:981-90
   PubMed Web of Science ®Google Scholar
• Jenkins AL, Bootman MD, Taylor CW, et al. Characterization of the receptor responsible for thrombin-induced intracellular calcium responses in osteoblast-like cells. J Biol Chem 1993;268:21432-7
   Google Scholar
• Abraham LA, Jenkins AL, Stone SR, et al. Expression of the thrombin receptor in developing bone and associated tissues. J Bone Miner Res 1998;13:818-27
   Google Scholar
• Abraham LA, MacKie EJ. Modulation of osteoblast-like cell behavior by activation of protease-activated receptor-1. J Bone Miner Res 1999;14:1320-9
   Google Scholar
• 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 2013; Epub ahead of print
   Web of Science ®Google Scholar
• McDougall JJ. Peripheral analgesia: hitting pain where it hurts. Biochim Biophys Acta 2011;1812:459-67
   Google Scholar