The complement system component C5a produces thermal hyperalgesia via macrophage-to-nociceptor signaling that requires NGF and TRPV1

Journal of Neuroscience

Volumn 36, Issue 18, 2016, Pages 5055-5070

  Shutov, Leonid P ^a   Warwick, Charles A ^a   Shi, Xiaoyu ^b   Gnanasekaran, Aswini ^a   Shepherd, Andrew J ^a,c   Mohapatra, Durga P ^a,c   Woodruff, Trent M ^d   David Clark, J ^b   Usachev, Yuriy M ^a  

^a UNIVERSITY OF IOWA   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

C5a; C5aR1; Complement; Macrophage; NGF; TRPV1

Indexed keywords

COLONY STIMULATING FACTOR; COMPLEMENT COMPONENT C5A; FREUND ADJUVANT; NERVE GROWTH FACTOR ANTIBODY; VANILLOID RECEPTOR 1; 3-(4-T-BUTYLPHENYL)-N-(2,3-DIHYDROBENZO(B)(1,4)DIOXIN-6-YL)ACRYLAMIDE; ACRYLAMIDE DERIVATIVE; FUSED HETEROCYCLIC RINGS; NERVE GROWTH FACTOR; TRPV1 PROTEIN, MOUSE; VANILLOID RECEPTOR;

ANIMAL BEHAVIOR; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; GENETIC TRANSFECTION; HYPERALGESIA; IMMUNOCYTOCHEMISTRY; IMMUNOHISTOCHEMISTRY; INFLAMMATORY PAIN; MALE; MOUSE; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SENSITIVITY ANALYSIS; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; C57BL MOUSE; CELL COMMUNICATION; CHEMICALLY INDUCED; FEMALE; GENETICS; HEAT; INFLAMMATION; MACROPHAGE; METABOLISM; PAIN RECEPTOR; PATHOLOGY; PATHOPHYSIOLOGY; PHYSICAL STIMULATION; SIGNAL TRANSDUCTION;

ACRYLAMIDES; ANIMALS; BRIDGED BICYCLO COMPOUNDS, HETEROCYCLIC; CELL COMMUNICATION; COMPLEMENT C5A; FEMALE; HOT TEMPERATURE; HYPERALGESIA; INFLAMMATION; MACROPHAGES; MALE; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; NERVE GROWTH FACTOR; NOCICEPTORS; PHYSICAL STIMULATION; SIGNAL TRANSDUCTION; TRPV CATION CHANNELS;

EID: 84965062058     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3249-15.2016     Document Type: Article

References (123)

1. Albaugh P, Fan Y, Mi Y, Sun F, Adrian F, Li N, Jia Y, Sarkisova Y, Kreusch A, Hood T, Lu M, Liu G, Huang S, Liu Z, Loren J, Tuntland T, Karanewsky DS, Seidel HM, Molteni V (2012) Discovery of GNF-5837, a selective TRK inhibitor with efficacy in rodent cancer models. ACS Med Chem Lett 3: 140-145. CrossRef Medline
2. Ali H, Fisher I, Haribabu B, Richardson RM, Snyderman R (1997) Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor. J Biol Chem 272: 11706-11709. CrossRef Medline
3. Andratsch M, Mair N, Constantin CE, Scherbakov N, Benetti C, Quarta S, Vogl C, Sailer CA, Uceyler N, Brockhaus J, Martini R, Sommer C, Zeilhofer HU, Müller W, Kuner R, Davis JB, Rose-John S, KressM (2009) A key role for gp130 expressed on peripheral sensory nerves in pathological pain. J Neurosci 29: 13473-13483. CrossRef Medline
4. Ayer-LeLievre C, Olson L, Ebendal T, Seiger A, Persson H (1988) Expression of the beta-nerve growth factor gene in hippocampal neurons. Science 240: 1339-1341. CrossRef Medline
5. Benson MJ, Thomas NK, Talwar S, Hodson MP, Lynch JW, Woodruff TM, Borges K (2015) A novel anticonvulsant mechanism via inhibition of complement receptor C5ar1 in murine epilepsy models. Neurobiol Dis 76: 87-97. CrossRef Medline
6. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4: 517-529. CrossRef Medline
7. BhatiaM (2005) Inflammatory response on the pancreatic acinar cell injury. Scand J Surg 94: 97-102. Medline
8. Bhave G, Gereau RW 4th (2004) Posttranslational mechanisms of peripheral sensitization. J Neurobiol 61: 88-106. CrossRef Medline
9. Bleasdale JE, Thakur NR, Gremban RS, Bundy GL, Fitzpatrick FA, Smith RJ, Bunting S (1990) Selective inhibition of receptor-coupled phospholipase C-dependent processes in human platelets and polymorphonuclear neutrophils. J Pharmacol Exp Ther 255: 756-768. Medline
10. Brennan FH, Anderson AJ, Taylor SM, Woodruff TM, Ruitenberg MJ (2012) Complement activation in the injured central nervous system: another dual-edged sword? J Neuroinflammation 9: 137. CrossRef Medline
11. Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ (2015) The complement receptor C5aR controls acute inflammation and astrogliosis following spinal cord injury. J Neurosci 35: 6517-6531. CrossRef Medline
12. Burnett SH, Kershen EJ, Zhang J, Zeng L, Straley SC, Kaplan AM, Cohen DA (2004) Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene. J Leukoc Biol 75: 612-623. CrossRef Medline
13. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389: 816-824. CrossRef Medline
14. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, JuliusD (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288: 306-313. CrossRef Medline
15. Chen MG, Schooley JC (1970) Effects of ionizing radiation and vinblastine on the proliferation of peritoneal macrophage precursors in the mouse. Radiat Res 41: 623-636. CrossRef Medline
16. Cheng HT, Dauch JR, Hayes JM, Hong Y, Feldman EL (2009) Nerve growth factor mediates mechanical allodynia in a mouse model of type 2 diabetes. J Neuropathol Exp Neurol 68: 1229-1243. CrossRef Medline
17. Cheng HT, Dauch JR, Oh SS, Hayes JM, Hong Y, Feldman EL (2010) p38 mediates mechanical allodynia in a mouse model of type 2 diabetes. Mol Pain 6: 28. CrossRef Medline
18. Cho SW, Soki FN, Koh AJ, Eber MR, Entezami P, Park SI, van Rooijen N, McCauley LK (2014) Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. Proc Natl Acad Sci U S A 111: 1545-1550. CrossRef Medline
19. Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411: 957-962. CrossRef Medline
20. Clapham DE (2007) Calcium signaling. Cell 131: 1047-1058. CrossRef Medline
21. Clark JD, Qiao Y, Li X, Shi X, Angst MS, Yeomans DC (2006) Blockade of the complement C5a receptor reduces incisional allodynia, edema, and cytokine expression. Anesthesiology 104: 1274-1282. CrossRef Medline
22. Collins F, Crutcher KA (1985) Neurotrophic activity in the adult rat hippocampal formation: regional distribution and increase after septal lesion. J Neurosci 5: 2809-2814. Medline
23. Constantin CE, Mair N, Sailer CA, Andratsch M, Xu ZZ, Blumer MJ, Scherbakov N, Davis JB, Bluethmann H, Ji RR, Kress M (2008) Endogenous tumor necrosis factor alpha (TNFalpha) requires TNF receptor type 2 to generate heat hyperalgesia in a mouse cancer model. J Neurosci 28: 5072-5081. CrossRef Medline
24. Davies LC, Jenkins SJ, Allen JE, Taylor PR (2013) Tissue-resident macrophages. Nat Immunol 14: 986-995. CrossRef Medline
25. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405: 183-187. CrossRef Medline
26. Desai BN, Leitinger N (2014) Purinergic and calcium signaling in macrophage function and plasticity. Front Immunol 5: 580. CrossRef Medline
27. Eskander MA, Ruparel S, Green DP, Chen PB, Por ED, Jeske NA, Gao X, Flores ER, Hargreaves KM (2015) Persistent nociception triggered by nerve growth factor (NGF) is mediated by TRPV1 and oxidative mechanisms. J Neurosci 35: 8593-8603. CrossRef Medline
28. Fosse E, Mollnes TE, Ingvaldsen B (1987) Complement activation during major operations with or without cardiopulmonary bypass. J Thorac Cardiovasc Surg 93: 860-866. Medline
29. Fric J, Zelante T, Wong AY, Mertes A, Yu HB, Ricciardi-Castagnoli P (2012) NFAT control of innate immunity. Blood 120: 1380-1389. CrossRef Medline
30. Galeotti N, Stefano GB, Guarna M, Bianchi E, Ghelardini C (2006) Signaling pathway of morphine induced acute thermal hyperalgesia in mice. Pain 123: 294-305. CrossRef Medline
31. Garaci E, Caroleo MC, Aloe L, Aquaro S, Piacentini M, Costa N, Amendola A, Micera A, Calio` R, Perno CF, Levi-Montalcini R (1999) Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV. Proc Natl Acad Sci U S A 96: 14013-14018. CrossRef Medline
32. Gold MS, Reichling DB, Shuster MJ, Levine JD (1996) Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc Natl Acad Sci U S A 93: 1108-1112. CrossRef Medline
33. Grant EP, Picarella D, Burwell T, Delaney T, Croci A, Avitahl N, Humbles AA, Gutierrez-Ramos JC, Briskin M, Gerard C, Coyle AJ (2002) Essential role for the C5a receptor in regulating the effector phase of synovial infiltration and joint destruction in experimental arthritis. J Exp Med 196: 1461-1471. CrossRef Medline
34. Gregory NS, Harris AL, Robinson CR, Dougherty PM, Fuchs PN, Sluka KA (2013) An overview of animal models of pain: disease models and outcome measures. J Pain 14: 1255-1269. CrossRef Medline
35. Griffin RS, Costigan M, Brenner GJ, Ma CH, Scholz J, Moss A, Allchorne AJ, Stahl GL, Woolf CJ (2007) Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. J Neurosci 27: 8699-8708. CrossRef Medline
36. 2++ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440-3450. Medline
37. Guo A, Vulchanova L, Wang J, Li X, Elde R (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11: 946-958. CrossRef Medline
38. HolersVM (2014) Complement and its receptors: new insights into human disease. Annu Rev Immunol 32: 433-459. CrossRef Medline
39. Hume DA, Perry VH, Gordon S (1984) The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages associated with epithelia. Anat Rec 210: 503-512. CrossRef Medline
40. Imai Y, Ibata I, Ito D, Ohsawa K, Kohsaka S (1996) A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys ResCommun 224: 855-862. CrossRef Medline
41. Immke DC, Gavva NR (2006) The TRPV1 receptor and nociception. Semin Cell Dev Biol 17: 582-591. CrossRef Medline
42. Jang JH, Clark JD, Li X, Yorek MS, Usachev YM, Brennan TJ (2010) Nociceptive sensitization by complement C5a and C3a in mouse. Pain 148: 343-352. CrossRef Medline
43. Jang JH, Liang D, Kido K, Sun Y, Clark DJ, Brennan TJ (2011) Increased local concentration of complement C5a contributes to incisional pain in mice. J Neuroinflammation 8: 80. CrossRef Medline
44. Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36: 57-68. CrossRef Medline
45. Ji RR, Xu ZZ, Gao YJ (2014) Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov 13: 533-548. CrossRef Medline
46. Jose PJ, Moss IK, Maini RN, Williams TJ (1990) Measurement of the chemotactic complement fragment C5a in rheumatoid synovial fluids by radioimmunoassay: role of C5a in the acute inflammatory phase. Ann Rheum Dis 49: 747-752. CrossRef Medline
47. Jung H, Toth PT, White FA, Miller RJ (2008) Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem 104: 254-263. CrossRef Medline
48. Kemper C, Pangburn MK, Fishelson Z (2014) Complement nomenclature 2014. Mol Immunol 61: 56-58. CrossRef Medline
49. Khan AA, Diogenes A, Jeske NA, Henry MA, Akopian A, Hargreaves KM (2008) Tumor necrosis factor alpha enhances the sensitivity of rat trigeminal neurons to capsaicin. Neuroscience 155: 503-509. CrossRef Medline
50. Kiener HP, Baghestanian M, Dominkus M, Walchshofer S, Ghannadan M, Willheim M, Sillaber C, Graninger WB, Smolen JS, Valent P (1998) Expression of the C5a receptor (CD88) on synovial mast cells in patients with rheumatoid arthritis. Arthritis Rheum 41: 233-245. CrossRef Medline
51. Klos A, Wende E, Wareham KJ, Monk PN (2013) International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev 65: 500-543. CrossRef Medline
52. Kwon MJ, Kim J, Shin H, Jeong SR, Kang YM, Choi JY, Hwang DH, Kim BG (2013) Contribution of macrophages to enhanced regenerative capacity of dorsal root ganglia sensory neurons by conditioning injury. J Neurosci 33: 15095-15108. CrossRef Medline
53. LaCroix-Fralish ML, Austin JS, Zheng FY, Levitin DJ, Mogil JS (2011) Patterns of pain: meta-analysis of microarray studies of pain. Pain 152: 1888-1898. CrossRef Medline
54. Lehmann DM, Seneviratne AM, Smrcka AV (2008) Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation. Mol Pharmacol 73: 410-418. Medline
55. Levin ME, Jin JG, Ji RR, Tong J, Pomonis JD, Lavery DJ, Miller SW, Chiang LW (2008) Complement activation in the peripheral nervous system following the spinal nerve ligation model of neuropathic pain. Pain 137: 182-201. CrossRef Medline
56. Levine JD, Gooding J, Donatoni P, Borden L, Goetzl EJ (1985) The role of the polymorphonuclear leukocyte in hyperalgesia. J Neurosci 5: 3025-3029. Medline
57. Li M, Peake PW, Charlesworth JA, Tracey DJ, Moalem-Taylor G (2007) Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats. Eur J Neurosci 26: 3486-3500. CrossRef Medline
58. Liang DY, Li X, Shi X, Sun Y, Sahbaie P, Li WW, Clark JD (2012) The complement component C5a receptor mediates pain and inflammation in a postsurgical pain model. Pain 153: 366-372. CrossRef Medline
59. Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM (2013) C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB J 27: 855-864. CrossRef Medline
60. Lindauer ML, Wong J, Iwakura Y, Magun BE (2009) Pulmonary inflamma-tion triggered by ricin toxin requires macrophages and IL-1 signaling. J Immunol 183: 1419-1426. CrossRef Medline
61. Loo L, Shepherd AJ, Mickle AD, Lorca RA, Shutov LP, Usachev YM, Mohapatra DP (2012) The C-type natriuretic peptide induces thermal hyperalgesia through a noncanonical Gbetagamma-dependent modulation of TRPV1 channel. J Neurosci 32: 11942-11955. CrossRef Medline
62. Lopshire JC, NicolGD (1998) The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and single-channel studies. J Neurosci 18: 6081-6092. Medline
63. Mallat M, Houlgatte R, Brachet P, Prochiantz A (1989) Lipopolysaccharidestimulated rat brain macrophages release NGF in vitro. Dev Biol 133: 309-311. CrossRef Medline
64. Manthey HD, Woodruff TM, Taylor SM, Monk PN (2009) Complement component 5a (C5a). Int J Biochem Cell Biol 41: 2114-2117. CrossRef Medline
65. Mantyh PW, Koltzenburg M, Mendell LM, Tive L, Shelton DL (2011) Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology 115: 189-204. CrossRef Medline
66. March DR, Proctor LM, Stoermer MJ, Sbaglia R, Abbenante G, Reid RC, Woodruff TM, Wadi K, Paczkowski N, Tyndall JD, Taylor SM, Fairlie DP (2004) Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes: relationships between structures and activity. Mol Pharmacol 65: 868-879. CrossRef Medline
67. Marchand F, Perretti M, McMahon SB (2005) Role of the immune system in chronic pain. Nat Rev Neurosci 6: 521-532. CrossRef Medline
68. Marcinkiewicz M, Marcinkiewicz J, Chen A, Leclaire F, Chrétien M, Richardson P (1999) Nerve growth factor and proprotein convertases furin and PC7 in transected sciatic nerves and in nerve segments cultured in conditioned media: their presence in Schwann cells, macrophages, and smooth muscle cells. J Comp Neurol 403: 471-485. CrossRef Medline
69. Martin F, Olsson NO, Jeannin JF (1981) Effects of four agents that modify microtubules and microfilaments (vinblastine, colchicine, lidocaine and cytochalasin B) on macrophage-mediated cytotoxicity to tumor cells. Cancer Immunol Immunother 1981: 113-119.
70. McCarthy C, Walker E (2014) Tropomyosin receptor kinase inhibitors: a patent update 2009-2013. Expert Opin Ther Pat 24: 731-744. CrossRef Medline
71. Mickle AD, Shepherd AJ, MohapatraDP (2015a) Sensory TRP channels: the key transducers of nociception and pain. Prog Mol Biol Transl Sci 131: 73-118. CrossRef Medline
72. Mickle AD, Shepherd AJ, Loo L, Mohapatra DP (2015b) Induction of thermal and mechanical hypersensitivity by parathyroid hormone-related peptide through upregulation of TRPV1 function and trafficking. Pain 156: 1620-1636. CrossRef Medline
73. Monk PN, Scola AM, Madala P, Fairlie DP (2007) Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol 152: 429-448. CrossRef Medline
74. Moriconi A, Cunha TM, Souza GR, Lopes AH, Cunha FQ, Carneiro VL, Pinto LG, Brandolini L, Aramini A, Bizzarri C, Bianchini G, Beccari AR, Fanton M, Bruno A, Costantino G, Bertini R, Galliera E, Locati M, Ferreira SH, Teixeira MM, et al. (2014) Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief. Proc Natl Acad SciU S A 111: 16937-16942. CrossRef Medline
75. Nathan CF (1987) Secretory products of macrophages. J Clin Invest 79: 319-326. CrossRef Medline
76. Obata K, Tsujino H, Yamanaka H, Yi D, Fukuoka T, Hashimoto N, Yonenobu K, Yoshikawa H, Noguchi K (2002) Expression of neurotrophic factors in the dorsal root ganglion in a rat model of lumbar disc herniation. Pain 99: 121-132. CrossRef Medline
77. O’Brien J, Martinson H, Durand-Rougely C, Schedin P (2012) Macrophages are crucial for epithelial cell death and adipocyte repopulation during mammary gland involution. Development 139: 269-275. CrossRef Medline
78. 2++ ionophore. Cell Immunol 75: 242-254. CrossRef Medline
79. Oppermann M, Götze O (1994) Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors. Immunology 82: 516-521. Medline
80. Patapoutian A, Tate S, Woolf CJ (2009) Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov 8: 55-68. CrossRef Medline
81. Pezet S, McMahon SB (2006) Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci 29: 507-538. CrossRef Medline
82. Proctor LM, Woodruff TM, Sharma P, Shiels IA, Taylor SM (2006) Transdermal pharmacology of small molecule cyclic C5a antagonists. Adv Exp Med Biol 586: 329-345. CrossRef Medline
83. Ray A, Dittel BN (2010) Isolation of mouse peritoneal cavity cells. J Vis Exp 35: pii1488. CrossRef Medline
84. 2++ responses by G{alpha}i-and G{alpha}q-coupled G-protein-coupled receptors require a single PLC{beta} isoform that is sensitive to both G{beta}{gamma} and G{alpha}q. J Biol Chem 286: 942-951. CrossRef Medline
85. Ren K, Dubner R (2010) Interactions between the immune and nervous systems in pain. Nat Med 16: 1267-1276. CrossRef Medline
86. Ricklin D, Lambris JD (2013) Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol 190: 3831-3838. CrossRef Medline
87. Roach TI, Rebres RA, Fraser ID, Decamp DL, Lin KM, Sternweis PC, Simon MI, Seaman WE (2008) Signaling and cross-talk by C5a and UDP in macrophages selectively use PLCbeta3 to regulate intracellular free calcium. J Biol Chem 283: 17351-17361. CrossRef Medline
88. Roxvall L, Bengtson A, Heideman M (1989) Anaphylatoxin generation in acute pancreatitis. J Surg Res 47: 138-143. CrossRef Medline
89. Runnels LW, Yue L, Clapham DE (2002) The TRPM7 channel is inactivated by PIP(2) hydrolysis. Nat Cell Biol 4: 329-336. CrossRef Medline
90. Russell FA, Fernandes ES, Courade JP, Keeble JE, Brain SD (2009) Tumour necrosis factor alpha mediates transient receptor potential vanilloid 1-dependent bilateral thermal hyperalgesia with distinct peripheral roles of interleukin-1beta, protein kinase C and cyclooxygenase-2 signalling. Pain 142: 264-274. CrossRef Medline
91. Sasmono RT, Oceandy D, Pollard JW, Tong W, Pavli P, Wainwright BJ, Ostrowski MC, Himes SR, Hume DA (2003) A macrophage colonystimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood 101: 1155-1163. CrossRef Medline
92. Schnizler K, Shutov LP, Van Kanegan MJ, Merrill MA, Nichols B, McKnight GS, Strack S, Hell JW, Usachev YM (2008) Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons. J Neurosci 28: 4904-4917. CrossRef Medline
93. Shelton DL, Reichardt LF (1986) Studies on the expression of the beta nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. Proc Natl Acad Sci U S A 83: 2714-2718. CrossRef Medline
94. Shepherd AJ, Mohapatra DP (2012) Tissue preparation and immunostaining of mouse sensory nerve fibers innervating skin and limb bones. J Vis Exp 59: e3485. CrossRef Medline
95. 2++]i and their determination using fluorescent probes. J Biol Chem 266: 1410-1414. Medline
96. Sorkin LS, SchafersM (2007) Immune cells in peripheral nerve. In: Immune and glial regulation of pain (DeLeo JA, Sorkin LS, Watkins LR, eds), pp 3-20. Seattle: International Association for the Study of Pain.
97. Soruri A, Kim S, Kiafard Z, Zwirner J (2003) Characterization of C5aR expression on murine myeloid and lymphoid cells by the use of a novel monoclonal antibody. Immunol Lett 88: 47-52. CrossRef Medline
98. Stein AT, Ufret-Vincenty CA, Hua L, Santana LF, Gordon SE (2006) Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J Gen Physiol 128: 509-522. CrossRef Medline
99. Stein C, Millan MJ, Herz A (1988) Unilateral inflammation of the hindpaw in rats as a model of prolonged noxious stimulation: alterations in behavior and nociceptive thresholds. Pharmacol Biochem Behav 31: 445-451. CrossRef Medline
100. Stephan AH, Barres BA, Stevens B (2012) The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci 35: 369-389. CrossRef Medline
101. Stucky CL, Koltzenburg M, Schneider M, Engle MG, Albers KM, Davis BM (1999) Overexpression of nerve growth factor in skin selectively affects the survival and functional properties of nociceptors. J Neurosci 19: 8509-8516. Medline
102. Ting E, Guerrero AT, Cunha TM, Verri WA Jr, Taylor SM, Woodruff TM, Cunha FQ, Ferreira SH (2008) Role of complement C5a in mechanical inflammatory hypernociception: potential use of C5a receptor antagonists to control inflammatory pain. Br J Pharmacol 153: 1043-1053. CrossRef Medline
103. Tordjmann T, Berthon B, Jacquemin E, Clair C, Stelly N, Guillon G, Claret M, Combettes L (1998) Receptor-oriented intercellular calcium waves evoked by vasopressin in rat hepatocytes. EMBO J 17: 4695-4703. CrossRef Medline
104. Tschernig T, Kiafard Z, Dibbert C, Neumann D, Zwirner J (2007) Use of monoclonal antibodies to assess expression of anaphylatoxin receptors in rat and murine models of lung inflammation. Exp Toxicol Pathol 58: 419-425. CrossRef Medline
105. Twining CM, Sloane EM, Schoeniger DK, Milligan ED, Martin D, Marsh H, Maier SF, Watkins LR (2005) Activation of the spinal cord complement cascade might contribute to mechanical allodynia induced by three animal models of spinal sensitization. J Pain 6: 174-183. CrossRef Medline
106. 2++ utilization. Mol Biol Cell 3: 335-347. CrossRef Medline
107. Vardanyan A, Wang R, Vanderah TW, Ossipov MH, Lai J, Porreca F, King T (2009) TRPV1 receptor in expression of opioid-induced hyperalgesia. J Pain 10: 243-252. CrossRef Medline
108. Veerhuis R, Nielsen HM, Tenner AJ (2011) Complement in the brain. Mol Immunol 48: 1592-1603. CrossRef Medline
109. Vega-Avelaira D, Géranton SM, FitzgeraldM (2009) Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury. Mol Pain 5: 70. CrossRef Medline
110. Wagner E, FrankMM (2010) Therapeutic potential of complement modulation. Nat Rev Drug Discov 9: 43-56. CrossRef Medline
111. Wang J, Hancock MK, Dudek JM, Bi K (2008) Cellular assays for highthroughput screening for modulators of Trk receptor tyrosine kinases. Curr Chem Genomics 1: 27-33. CrossRef Medline
112. Wang NK, Lai CC, Liu CH, Yeh LK, Chou CL, Kong J, Nagasaki T, Tsang SH, Chien CL (2013) Origin of fundus hyperautofluorescent spots and their role in retinal degeneration in a mouse model of Goldmann-Favre syndrome. Dis Model Mech 6: 1113-1122. CrossRef Medline
113. Wang Q, Rozelle AL, Lepus CM, Scanzello CR, Song JJ, Larsen DM, Crish JF, Bebek G, Ritter SY, Lindstrom TM, Hwang I, Wong HH, Punzi L, Encarnacion A, Shamloo M, Goodman SB, Wyss-Coray T, Goldring SR, Banda NK, Thurman JM, et al. (2011) Identification of a central role for complement in osteoarthritis. Nat Med 17: 1674-1679. CrossRef Medline
114. Wang Z, Liu B, Wang P, Dong X, Fernandez-Hernando C, Li Z, Hla T, Claffey K, Smith JD, Wu D (2008) Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice. J Clin Invest 118: 195-204. CrossRef Medline
115. White FA, Jung H, Miller RJ (2007) Chemokines and the pathophysiology of neuropathic pain. Proc Natl Acad Sci U S A 104: 20151-20158. CrossRef Medline
116. Wild KD, Bian D, Zhu D, Davis J, Bannon AW, Zhang TJ, Louis JC (2007) Antibodies to nerve growth factor reverse established tactile allodynia in rodent models of neuropathic pain without tolerance. J Pharmacol Exp Ther 322: 282-287. CrossRef Medline
117. Woodruff TM, Strachan AJ, Dryburgh N, Shiels IA, Reid RC, Fairlie DP, Taylor SM (2002) Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis Rheum 46: 2476-2485. CrossRef Medline
118. Woodruff TM, Crane JW, Proctor LM, Buller KM, Shek AB, de Vos K, Pollitt S, Williams HM, Shiels IA, Monk PN, Taylor SM (2006) Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration. FASEB J 20: 1407-1417. CrossRef Medline
119. 2++ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med 14: 738-747. CrossRef Medline
120. Yue X, Favot P, Dunn TL, Cassady AI, Hume DA (1993) Expression of mRNA encoding the macrophage colony-stimulating factor receptor (c-fms) is controlled by a constitutive promoter and tissue-specific transcription elongation. Mol Cell Biol 13: 3191-3201. CrossRef Medline
121. Zhang N, Inan S, Cowan A, Sun R, Wang JM, Rogers TJ, Caterina M, Oppenheim JJ (2005a) A proinflammatory chemokine, CCL3, sensitizes the heat-and capsaicin-gated ion channel TRPV1. Proc Natl Acad Sci U S A 102: 4536-4541. CrossRef Medline
122. Zhang X, Huang J, McNaughton PA (2005b) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24: 4211-4223. CrossRef Medline
123. Zhu W, Oxford GS (2007) Phosphoinositide-3-kinase and mitogen activated protein kinase signaling pathways mediate acute NGF sensitization of TRPV1. Mol Cell Neurosci 34: 689-700. CrossRef Medline