The role of thrombin and protease-activated receptors in pain mechanisms

Thrombosis and Haemostasis

Volumn 103, Issue 6, 2010, Pages 1145-1151

  García, Paul S ^a   Gulati, Amitabh ^a   Levy, Jerrold H ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Coagulation; Hemostasis; Inflammation; Pain; Protease activated receptor; Thrombin

Indexed keywords

PROTEINASE ACTIVATED RECEPTOR 1; PROTEINASE ACTIVATED RECEPTOR 2; PROTEINASE ACTIVATED RECEPTOR 3; PROTEINASE ACTIVATED RECEPTOR 4; THROMBIN; PROTEINASE ACTIVATED RECEPTOR;

BLOOD CLOTTING; CELL ACTIVATION; HEMOSTASIS; HUMAN; INFLAMMATION; MICROGLIA; NERVE FIBER C; NEUROPHYSIOLOGY; NOCICEPTION; PAIN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SPINAL CORD; ANIMAL; APOPTOSIS; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM; COLITIS; DISEASE MODEL; DRUG EFFECTS; METABOLISM; NERVE CONDUCTION; NERVOUS SYSTEM DEVELOPMENT; PAIN RECEPTOR; PANCREATITIS;

ANIMALS; APOPTOSIS; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM; COLITIS; DISEASE MODELS, ANIMAL; HUMANS; NEURAL CONDUCTION; NEUROGENESIS; NOCICEPTORS; PAIN; PANCREATITIS; RECEPTORS, PROTEINASE-ACTIVATED; THROMBIN;

EID: 77953146780     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH09-12-0848     Document Type: Review

References (79)

1. Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002; 5 (Suppl): 1062-1067.
2. Argoff CE, et al. Multimodal analgesia for chronic pain: rationale and future directions. Pain Med 2009; 10 (Suppl 2): S53-66.
3. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009; 10: 895-926.
4. Seybold VS. The role of peptides in central sensitization. Handb Exp Pharmacol 2009; 194: 451-491.
5. Miller RJ, et al. Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol 2009; 194: 417-449.
6. Russell FA, McDougall JJ. Proteinase activated receptor (PAR) involvement in mediating arthritis pain and inflammation. Inflamm Res 2009; 58: 119-126.
7. Bunnett NW. Protease-activated receptors: how proteases signal to cells to cause inflammation and pain. Semin Thromb Hemost 2006; 32 (Suppl 1): 39-48.
8. Santilli F, Davi G. Thrombin as a common downstream target blocking both platelet and monocyte activation. Thromb Haemost 2009; 101: 220-221.
9. Stassen JM, et al. The hemostatic system. Curr Med Chem 2004; 11: 2245-2260.
10. Martorell L, et al. Thrombin and protease-activated receptors (PARs) in atherothrombosis. Thromb Haemost 2008; 99: 305-315.
11. Dugina TN, 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: 463-546
12. Donovan FM, et al. Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and RhoA activities. J Neurosci 1997; 17: 5316-5326.
13. Patwardhan AM, et al. PAR-2 agonists activate trigeminal nociceptors and induce functional competence in the delta opioid receptor. Pain 2006; 125: 114-124.
14. Esmon CT. The impact of the inflammatory response on coagulation. Thromb Res 2004; 114: 321-327.
15. Fredenburgh JC, et al. Modes and consequences of thrombin's interaction with fibrin. Biophys Chem 2004; 112: 277-284.
16. Di Cera E. Thrombin interactions. Chest 2003; 124 (3 Suppl): 11S-17S.
17. Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev 2007; 21: 131-142.
18. Allen GA, et al. Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system. J Thromb Haemost 2004; 2: 402-413.
19. Wolberg AS. Thrombin generation assays: understanding how the method influences the results. Thromb Res 2007; 119: 663-665.
20. Turgeon VL, et al. Thrombin: a neuronal cell modulator. Thromb Res 2000; 99: 417-427.
21. Turgeon VL, et al. Activation of the protease-activated thrombin receptor (PAR)-1 induces motoneuron degeneration in the developing avian embryo. J Neuropathol Exp Neurol 1999; 58: 499-504.
22. Smirnova IV, et al. Thrombin is an extracellular signal that activates intracellular death protease pathways inducing apoptosis in model motor neurons. J Neurobiol 1998; 36: 64-80.
23. Faraut B, et al. Thrombin reduces MuSK and acetylcholine receptor expression along with neuromuscular contact size in vitro. Eur J Neurosci 2004; 19: 2099-2108.
24. Gill JS, et al. Thrombin induced inhibition of neurite outgrowth from dorsal root ganglion neurons. Brain Res 1998; 797: 321-327.
25. Suo Z, et al. Thrombin: a potential proinflammatory mediator in neurotrauma and neurodegenerative disorders. Curr Drug Targets Inflamm Allergy 2004; 3: 105-114.
26. Kyrle PA, et al. Inhibition rather than enhancement of hemostatic system activation during initiation of oral anticoagulant treatment. Thromb Haemost 1997; 77: 685-689.
27. Nishino A, et al. Thrombin may contribute to the pathophysiology of central nervous system injury. J Neurotrauma 1993; 10: 167-179.
28. Motohashi O, et al. Hirudin suppresses the invasion of inflammatory cells and the appearance of vimentin-positive astrocytes in the rat cerebral ablation model. J Neurotrauma 1997; 14: 747-754. (Pubitemid 27479415)
29. Lee KR, et al. Edema from intracerebral hemorrhage: the role of thrombin. J Neurosurg 1996; 84: 91-96.
30. Turgeon VL, Houenou LJ. The role of thrombin-like (serine) proteases in the development, plasticity and pathology of the nervous system. Brain Res Brain Res Rev 1997; 25: 85-95.
31. Sokolova E, Reiser G. Prothrombin/thrombin and the thrombin receptors PAR-1 and PAR-4 in the brain: localization, expression and participation in neurodegenerative diseases. Thromb Haemost 2008; 100: 576-581.
32. Vu TK, et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991; 64: 1057-1068.
33. Ossovskaya VS, Bunnett NW. Protease-activated receptors: contribution to physiology and disease. Physiol Rev 2004; 84: 579-621.
34. Nystedt S, et al. Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci USA 1994; 91: 9208-9212. (Pubitemid 24297883)
35. Ishihara H, et al. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 1997; 386: 502-506.
36. Kahn ML, et al. A dual thrombin receptor system for platelet activation. Nature 1998; 394: 690-694.
37. Xu WF, et al. Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci USA 1998; 95: 6642-6646.
38. Carreno-Muller E, et al. Thrombin induces in vivo degeneration of nigral dopaminergic neurones along with the activation of microglia. J Neurochem 2003; 84: 1201-1214.
39. Choi SH, et al. Thrombin-induced oxidative stress contributes to the death of hippocampal neurons in vivo: role of microglial NADPH oxidase. J Neurosci 2005; 25: 4082-4090.
40. Gingrich MB, et al. Potentiation of NMDA receptor function by the serine protease thrombin. J Neurosci 2000; 20: 4582-4595.
41. Zeng F, et al. Enhancement of NMDA receptor sensitivity by thrombin and its relationship with tissue transglutaminase. Zhonghua Nei Ke Za Zhi 2005; 44: 668-671.
42. Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 2005; 3: 1800-1814.
43. Cenac N, et al. Proteinase-activated receptor-1 is an anti-inflammatory signal for colitis mediated by a type 2 immune response. Inflamm Bowel Dis 2005; 11: 792-798.
44. Jesmin S, et al. Temporal changes in pulmonary expression of key procoagulant molecules in rabbits with endotoxin-induced acute lung injury: elevated expression levels of protease-activated receptors. Thromb Haemost 2004; 92: 966-979.
45. Mule F, et al. Evidence for the presence of functional protease activated receptor 4 (PAR4) in the rat colon. Gut 2004; 53: 229-234.
46. Megyeri M, et al. Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and endothelial function. J Immunol 2009; 183: 3409-3416.
47. Hirose T, et al. Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. J Cell Sci 2002; 115: 2485-2495. (Pubitemid 34778066)
48. Saito T, Bunnett NW. Protease-activated receptors: regulation of neuronal function. Neuromolecular Med 2005; 7: 79-99.
49. Cottrell GS, et al. Protease-activated receptor 2: activation, signalling and function. Biochem Soc Trans 2003; 31: 1191-1197. (Pubitemid 38030937)
50. Fang M, et al. Thrombin inhibits NMDA-mediated nociceptive activity in the mouse: possible mediation by endothelin. J Physiol 2003; 549: 903-917.
51. Tomimatsu Y, et al. Proteases involved in long-term potentiation. Life Sci 2002; 72: 355-361.
52. Kuroda R, Kawabata A. Pain information pathways from the periphery to the cerebral cortex. Yakugaku Zasshi 2003; 123: 533-546.
53. Vergnolle N, et al. Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci 2001; 22: 146-152.
54. de Garavilla L, et al. Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism. Br J Pharmacol 2001; 133: 975-987.
55. Green BT, et al. Intestinal type 2 proteinase-activated receptors: expression in opioid-sensitive secretomotor neural circuits that mediate epithelial ion transport. J Pharmacol Exp Ther 2000; 295: 410-416.
56. Cenac N, 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: 4296-4300. (Pubitemid 36428198)
57. Nguyen C, et al. Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism. Can J Physiol Pharmacol 2003; 81: 920-927.
58. Fiorucci S, Distrutti E. Role of PAR2 in pain and inflammation. Trends Pharmacol Sci 2002; 23: 153-155.
59. Asfaha S, et al. Proteinase-activated receptor-1 agonists attenuate nociception in response to noxious stimuli. Br J Pharmacol 2002; 135: 1101-1106. (Pubitemid 34259109)
60. Amadesi S, et al. Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci 2004; 24: 4300-4312.
61. Corvera CU, et al. Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2. J Physiol 1999; 517: 741-756.
62. Narita M, et al. Protease-activated receptor-1 and platelet-derived growth factor in spinal cord neurons are implicated in neuropathic pain after nerve injury. J Neurosci 2005; 25: 10000-10009.
63. Wu H, et al. The expression and the role of protease nexin-1 on brain edema after intracerebral hemorrhage. J Neurol Sci 2008; 270: 172-183.
64. Ding-Pfennigdorff D, et al. Stimulation of PAR-2 excites and sensitizes rat cutaneous C-nociceptors to heat. Neuroreport 2004; 15: 2071-2075.
65. Dai Y, 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: 4293-4299.
66. Kawabata A, et al. Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in nociception/hyperalgesia elicited by protease-activated receptor-2 activation in mice and rats. Neurosci Lett 2002; 329: 349-353.
67. Kawabata A, et al. Activation of trigeminal nociceptive neurons by parotid PAR-2 activation in rats. Neuroreport 2004; 15: 1617-1621.
68. Holzhausen M, et al. Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis. Mem Inst Oswaldo Cruz 2005; 100 (Suppl 1): 177-180. (Pubitemid 40685460)
69. Auge C, et al. Protease-activated receptor-4 (PAR 4): a role as inhibitor of visceral pain and hypersensitivity. Neurogastroenterol Motil 2009; 21: 1189-e107.
70. Hoogerwerf WA, et al. The proteinase-activated receptor 2 is involved in nociception. J Neurosci 2001; 21: 9036-9042.
71. Kirkup AJ, et al. Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats. J Physiol 2003; 552: 589-601.
72. Vergnolle N. Protease-activated receptors as drug targets in inflammation and pain. Pharmacol Ther 2009; 123: 292-309.
73. Thiagarajan P. New targets for antithrombotic drugs. Am J Cardiovasc Drugs 2002; 2: 227-235.
74. Hoogerwerf WA, et al. Trypsin mediates nociception via the proteinase-activated receptor 2: a potentially novel role in pancreatic pain. Gastroenterology 2004; 127: 883-891.
75. Maeda K, et al. Proinflammatory role of trypsin and protease-activated receptor-2 in a rat model of acute pancreatitis. Pancreas 2005; 31: 54-62.
76. Hoogerwerf WA, et al. The role of mast cells in the pathogenesis of pain in chronic pancreatitis. BMC Gastroenterol 2005; 5: 8.
77. Sharma A, et al. Protection against acute pancreatitis by activation of protease-activated receptor-2. Am J Physiol Gastrointest Liver Physiol 2005; 288: G388-395.
78. Serebruany VL, et al. Effect of statins on platelet PAR-1 thrombin receptor in patients with the metabolic syndrome (from the PAR-1 inhibition by statins [PARIS] study). Am J Cardiol 2006; 97: 1332-1336.
79. Paoloni JA, Orchard JW. The use of therapeutic medications for soft-tissue injuries in sports medicine. Med J Aust 2005; 183: 384-388.