Neuroinflammation and the generation of neuropathic pain

British Journal of Anaesthesia

Volumn 111, Issue 1, 2013, Pages 26-37

  Ellis, A ^a   Bennett, D L H ^b  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

immune response; pain, neuropathic

Indexed keywords

AUTACOID; BRADYKININ; BRAIN NATRIURETIC PEPTIDE; CATHEPSIN S; CD59 ANTIGEN; COMPLEMENT COMPONENT C3A; COMPLEMENT COMPONENT C5A; CORTICOSTEROID; CYCLIC AMP DEPENDENT PROTEIN KINASE; DILMAPIMOD; FRACTALKINE; GELATINASE B; GLUTAMIC ACID; HISTAMINE; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPOXIN; MINOCYCLINE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; MONOCYTE CHEMOTACTIC PROTEIN 1; PROPENTOFYLLINE; PROSTACYCLIN; PROSTAGLANDIN E2; PROTEIN KINASE C; SEROTONIN; STRESS ACTIVATED PROTEIN KINASE; SUBSTANCE P; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA ANTIBODY;

ANTIOXIDANT ACTIVITY; ASTROCYTE; BACKACHE; CELL ACTIVATION; CHEMOTAXIS; CHEMOTHERAPY; COMPLEX REGIONAL PAIN SYNDROME; DEGRANULATION; HELPER CELL; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; MACROPHAGE; MAST CELL; MICROGLIA; NERVE CELL; NERVE ENDING; NERVE INJURY; NERVOUS SYSTEM INFLAMMATION; NEUROPATHIC PAIN; NEUTROPHIL; PERIPHERAL NERVE INJURY; PHAGOCYTOSIS; POSTHERPETIC NEURALGIA; POSTOPERATIVE PAIN; PRIORITY JOURNAL; REVIEW; SCHWANN CELL; SENSORY NERVE CELL; SPINAL CORD DORSAL HORN; T LYMPHOCYTE;

EID: 84880206663     PISSN: 00070912     EISSN: 14716771     Source Type: Journal    
DOI: 10.1093/bja/aet128     Document Type: Article

References (140)

1. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008; 454: 428-35
2. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 2008; 8: 349-61
3. Calvo M, Dawes JM, Bennett DL. The role of the immune system in the generation of neuropathic pain. Lancet Neurol 2012; 11: 629-42
4. Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 2007; 10: 1361-8
5. Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci 2005; 6: 521-32
6. Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008; 70: 1630-5
7. Solaro C, Brichetto G, Amato MP, et al. The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study. Neurology 2004; 63: 919-21
8. Ruts L, Drenthen J, Jongen JL, et al. Pain in Guillain-Barre syndrome: a long-term follow-up study. Neurology 2010; 75: 1439-47
9. Napoli I, Noon LA, Ribeiro S, et al. A central role for the ERKsignaling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo. Neuron 2012; 73: 729-42
10. Allodi I, Udina E, Navarro X. Specificity of peripheral nerve regeneration: interactions at the axon level. Prog Neurobiol 2012; 98: 16-37
11. Perkins NM, Tracey DJ. Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 2000; 101: 745-57
12. Zuo Y, Perkins NM, Tracey DJ, Geczy CL. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 2003; 105: 467-79
13. Kim CF, Moalem-Taylor G. Detailed characterization of neuro-immune responses following neuropathic injury in mice. Brain Res 2011; 1405: 95-108
14. Smith FM, Haskelberg H, Tracey DJ, Moalem-Taylor G. Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury. Neuroimmunomodulation 2007; 14: 317-25
15. Kumar V, Sharma A. Neutrophils: Cinderella of innate immune system. Int Immunopharmacol 2010; 10: 1325-34
16. Moalem G, Xu K, Yu L. T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience 2004; 129: 767-77
17. Nathan CF. Secretory products of macrophages. J Clin Invest 1987; 79: 319-26
18. Liu T, van Rooijen N, Tracey DJ. Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain 2000; 86: 25-32
19. Palmer MT, Weaver CT. Autoimmunity: increasing suspects in the CD4+ T cell lineup. Nat Immunol 2010; 11: 36-40
20. Torii H, Hosoi J, Beissert S, et al. Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide. J Leukoc Biol 1997; 61: 216-23
21. Gonzalez HL, Carmichael N, Dostrovsky JO, Charlton MP. Evaluation of the time course of plasma extravasation in the skin by digital image analysis. J Pain 2005; 6: 681-8
22. 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
23. Wu G, Ringkamp M, Murinson BB, et al. Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents. J Neurosci 2002; 22: 7746-53
24. Taiwo YO, Levine JD. Prostaglandin effects after elimination of indirect hyperalgesic mechanisms in the skin of the rat. Brain Res 1989; 492: 397-9
25. Bennett DL, Koltzenburg M, Priestley JV, Shelton DL, McMahon SB. Endogenous nerve growth factor regulates the sensitivity of nociceptors in the adult rat. Eur J Neurosci 1998; 10: 1282-91
26. Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumour necrosis factoralpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 1997; 81: 255-62
27. Binshtok AM, Wang H, Zimmermann K, et al. Nociceptors are interleukin-1beta sensors. J Neurosci 2008; 28: 14062-73
28. Woolf CJ, Ma Q. Nociceptors-noxious stimulus detectors. Neuron 2007; 55: 353-64
29. Vellani V, Mapplebeck S, Moriondo A, Davis JB, McNaughton PA. Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J Physiol 2001; 534: 813-25
30. Crandall M, Kwash J, Yu W, White G. Activation of protein kinase C sensitizes human VR1 to capsaicin and to moderate decreases in pH at physiological temperatures in Xenopus oocytes. Pain 2002; 98: 109-17
31. Morenilla-Palao C, Planells-Cases R, Garcia-Sanz N, Ferrer-Montiel A. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem 2004; 279: 25665-72
32. Premkumar LS, Ahern GP. Induction of vanilloid receptor channel activity by protein kinase C. Nature 2000; 408: 985-90
33. Navarro X, Vivo M, Valero-Cabre A. Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 2007; 82: 163-201
34. Hudson LJ, Bevan S, Wotherspoon G, Gentry C, Fox A, Winter J. VR1 protein expression increases in undamaged DRG neurons after partial nerve injury. Eur J Neurosci 2001; 13: 2105-14
35. Ma W, Zhang Y, Bantel C, Eisenach JC. Medium and large injured dorsal root ganglion cells increase TRPV-1, accompanied by increased alpha2C-adrenoceptor co-expression and functional inhibition by clonidine. Pain 2005; 113: 386-94
36. Wang R, Guo W, Ossipov MH, Vanderah TW, Porreca F, Lai J. Glial cell line-derived neurotrophic factor normalizes neurochemical changes in injured dorsal root ganglion neurons and prevents the expression of experimental neuropathic pain. Neuroscience 2003; 121: 815-24
37. Fukuoka T, Tokunaga A, Kondo E, Miki K, Tachibana T, Noguchi K. Change in mRNAs for neuropeptides and the GABA(A) receptor in dorsal root ganglion neurons in a rat experimental neuropathic pain model. Pain 1998; 78: 13-26
38. Fukuoka T, Tokunaga A, Tachibana T, Dai Y, Yamanaka H, Noguchi K. VR1, but not P2X(3), increases in the spared L4 DRG in rats with L5 spinal nerve ligation. Pain 2002; 99: 111-20
39. Fukuoka T, Kondo E, Dai Y, Hashimoto N, Noguchi K. Brainderived neurotrophic factor increases in the uninjured dorsal root ganglion neurons in selective spinal nerve ligation model. J Neurosci 2001; 21: 4891-900
40. Wood JN, Boorman JP, Okuse K, Baker MD. Voltage-gated sodium channels and pain pathways. J Neurobiol 2004; 61: 55-71
41. 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
42. Nadeau S, Filali M, Zhang J, et al. Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1beta and TNF: implications for neuropathic pain. J Neurosci 2011; 31: 12533-42
43. Barrette B, Hebert MA, Filali M, et al. Requirement of myeloid cells for axon regeneration. J Neurosci 2008; 28: 9363-76
44. Morin N, Owolabi SA, Harty MW, et al. Neutrophils invade lumbar dorsal root ganglia after chronic constriction injury of the sciatic nerve. J Neuroimmunol 2007; 184: 164-71
45. Hu P, Bembrick AL, Keay KA, McLachlan EM. Immune cell involvement in dorsal root ganglia and spinal cord after chronic constriction or transection of the rat sciatic nerve. Brain Behav Immun 2007; 21: 599-616
46. Hu P, McLachlan EM. Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve lesions in the rat. Neuroscience 2002; 112: 23-38
47. Tanaka T, Minami M, Nakagawa T, Satoh M. Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain. Neurosci Res 2004; 48: 463-9
48. Nishida K, Kuchiiwa S, Oiso S, et al. Up-regulation of matrix metalloproteinase-3 in the dorsal root ganglion of rats with paclitaxel-induced neuropathy. Cancer Sci 2008; 99: 1618-25
49. Peters CM, Jimenez-Andrade JM, Jonas BM, et al. Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells. Exp Neurol 2007; 203: 42-54
50. Zhang ZY, Zhang Z, Fauser U, Schluesener HJ. Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocycline. J Cell Mol Med 2009; 13: 341-51
51. Fornoni A, Ijaz A, Tejada T, Lenz O. Role of inflammation in diabetic nephropathy. Curr Diabetes Rev 2008; 4: 10-7
52. Rivero A, Mora C, Muros M, Garcia J, Herrera H, Navarro-Gonzalez JF. Pathogenic perspectives for the role of inflammation in diabetic nephropathy. Clin Sci 2009; 116: 479-92
53. Luis-Rodriguez D, Martinez-Castelao A, Gorriz JL, De-Alvaro F, Navarro-Gonzalez JF. Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy. World J Diabetes 2012; 3: 7-18
54. Kieseier BC, Seifert T, Giovannoni G, Hartung HP. Matrix metalloproteinases in inflammatory demyelination: targets for treatment. Neurology 1999; 53: 20-5
55. Bujalska M, Tatarkiewicz J, Gumulka SW. Effect of bradykinin receptor antagonists on vincristine- and streptozotocin-induced hyperalgesia in a rat model of chemotherapy-induced and diabetic neuropathy. Pharmacology 2008; 81: 158-63
56. Uceyler N, Sommer C. Status of immune mediators in painful neuropathies. Curr Pain Headache Rep 2008; 12: 159-64
57. Beggs S, Liu XJ, Kwan C, Salter MW. Peripheral nerve injury and TRPV1-expressing primary afferent C-fibers cause opening of the blood-brain barrier. Mol Pain 2010; 6: 74
58. Echeverry S, Shi XQ, Rivest S, Zhang J. Peripheral nerve injury alters blood-spinal cord barrier functional and molecular integrity through a selective inflammatory pathway. J Neurosci 2011; 31: 10819-28
59. Cao L, DeLeo JA. CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur J Immunol 2008; 38: 448-58
60. Costigan M, Moss A, Latremoliere A, et al. T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J Neurosci 2009; 29: 14415-22
61. Vallejo R, Tilley DM, Vogel L, Benyamin R. The role of glia and the immune system in the development and maintenance of neuropathic pain. Pain Pract 2010; 10: 167-84
62. Beggs S, Trang T, Salter MW. P2X4R+ microglia drive neuropathic pain. Nat Neurosci 2012; 15: 1068-73
63. Calvo M, Bennett DL. The mechanisms of microgliosis and pain following peripheral nerve injury. Exp Neurol 2012; 234: 271-82
64. Zhang RX, Li A, Liu B, et al. IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats. Pain 2008; 135: 232-9
65. Scholz J, Abele A, Marian C, et al. Low-dose methotrexate reduces peripheral nerve injury-evoked spinal microglial activation and neuropathic pain behavior in rats. Pain 2008; 138: 130-42
66. Jin SX, Zhuang ZY, Woolf CJ, Ji RR. p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci 2003; 23: 4017-22
67. Tsuda M, Masuda T, Kitano J, Shimoyama H, Tozaki-Saitoh H, Inoue K. IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain. Proc Natl Acad Sci USA 2009; 106: 8032-7
68. Wen YR, Suter MR, Kawasaki Y, et al. Nerve conduction blockade in the sciatic nerve prevents but does not reverse the activation of p38 mitogen-activated protein kinase in spinal microglia in the rat spared nerve injury model. Anesthesiology 2007; 107: 312-21
69. Calvo M, Zhu N, Tsantoulas C, et al. Neuregulin-ErbB signaling promotes microglial proliferation and chemotaxis contributing to microgliosis and pain after peripheral nerve injury. J Neurosci 2010; 30: 5437-50
70. Takeda K, Muramatsu M, Chikuma T, Kato T. Effect of memantine on the levels of neuropeptides and microglial cells in the brain regions of rats with neuropathic pain. J Mol Neurosci 2009; 39: 380-90
71. Banati RB, Cagnin A, Brooks DJ, et al. Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury. Neuroreport 2001; 12: 3439-42
72. Del Valle L, Schwartzman RJ, Alexander G. Spinal cord histopathological alterations in a patient with longstanding complex regional pain syndrome. Brain Behav Immun 2009; 23: 85-91
73. Raghavendra V, Tanga F, DeLeo JA. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 2003; 306: 624-30
74. Ledeboer A, Sloane EM, Milligan ED, et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 2005; 115: 71-83
75. Tsuda M, Shigemoto-Mogami Y, Koizumi S, et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 2003; 424: 778-83
76. Hu JH, Yang JP, Liu L, et al. Involvement of CX3CR1 in bone cancer pain through the activation of microglia p38 MAPK pathway in the spinal cord. Brain Res 2012; 1465: 1-9
77. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron 2012; 73: 638-52
78. Blackbeard J, Wallace VC, O'Dea KP, et al. The correlation between pain-related behaviour and spinal microgliosis in four distinct models of peripheral neuropathy. Eur J Pain 2012; 16: 1357-67
79. Huang W, Calvo M, Krau K, et al. Ethologically relevant behavioural changes and peripheral nerve neuropathology in a rat model of HIV antiretroviral drug stavudine induced peripheral neuropathy. Pain 2013; 154: 560-75
80. Zheng FY, Xiao WH, Bennett GJ. The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries. Neuroscience 2011; 176: 447-54
81. Kiguchi N, Maeda T, Kobayashi Y, Kishioka S. Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice. Neurosci Lett 2008; 445: 140-3
82. Sweitzer SM, Pahl JL, DeLeo JA. Propentofylline attenuates vincristine-induced peripheral neuropathy in the rat. Neurosci Lett 2006; 400: 258-61
83. Talbot S, Chahmi E, Dias JP, Couture R. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy. J Neuroinflammation 2010; 7: 36
84. Wodarski R, Clark AK, Grist J, Marchand F, Malcangio M. Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. Eur J Pain 2009; 13: 807-11
85. Liao YH, Zhang GH, Jia D, et al. Spinal astrocytic activation contributes to mechanical allodynia in a mouse model of type diabetes. Brain Res 2011; 1368: 324-35
86. Kofuji P, Newman EA. Potassium buffering in the central nervous system. Neuroscience 2004; 129: 1045-56
87. De Leo JA, Tawfik VL, LaCroix-Fralish ML. The tetrapartite synapse: path to CNS sensitization and chronic pain. Pain 2006; 122: 17-21
88. Romero-Sandoval A, Chai N, Nutile-McMenemy N, Deleo JA. A comparison of spinal Iba1 and GFAP expression in rodent models of acute and chronic pain. Brain Res 2008; 1219: 116-26
89. Tanga FY, Raghavendra V, DeLeo JA. Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int 2004; 45: 397-407
90. Colburn RW, Rickman AJ, DeLeo JA. The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp Neurol 1999; 157: 289-304
91. Tanga FY, Raghavendra V, Nutile-McMenemy N, Marks A, Deleo JA. Role of astrocytic S100beta in behavioral hypersensitivity in rodent models of neuropathic pain. Neuroscience 2006; 140: 1003-10
92. Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia 2005; 50: 427-34
93. Ridet JL, Malhotra SK, Privat A, Gage FH. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 1997; 20: 570-7
94. Kim DS, Figueroa KW, Li KW, Boroujerdi A, Yolo T, Luo ZD. Profiling of dynamically changed gene expression in dorsal root ganglia post peripheral nerve injury and a critical role of injury-induced glial fibrillary acidic protein in maintenance of pain behaviors [corrected]. Pain 2009; 143: 114-22
95. Kawasaki Y, Zhang L, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factoralpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 2008; 28: 5189-94
96. Clark AK, Wodarski R, Guida F, Sasso O, Malcangio M. Cathepsin S release from primary cultured microglia is regulated by the P2X7 receptor. Glia 2010; 58: 1710-26
97. Clark AK, Yip PK, Malcangio M. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci 2009; 29: 6945-54
98. Coull JA, Beggs S, Boudreau D, et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005; 438: 1017-21
99. Coull JA, Boudreau D, Bachand K, et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003; 424: 938-42
100. Miletic G, Miletic V. Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn. Pain 2008; 137: 532-9
101. Ulmann L, Hatcher JP, Hughes JP, et al. Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain. J Neurosci 2008; 28: 11263-8
102. Horvath RJ, Romero-Sandoval EA, De Leo JA. Inhibition of microglial P2X4 receptors attenuates morphine tolerance, Iba1, GFAP and mu opioid receptor protein expression while enhancing perivascular microglial ED2. Pain 2010; 150: 401-13
103. Ferrini F, Trang T, Mattioli TA, et al. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci 2013; 16: 183-92
104. Wei F, Guo W, Zou S, Ren K, Dubner R. Supraspinal glial-neuronal interactions contribute to descending pain facilitation. J Neurosci 2008; 28: 10482-95
105. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005; 6: 1191-7
106. Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2001; 2: 612-9
107. Xu ZZ, Berta T, Ji RR. Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury. J Neuroimmune Pharmacol 2012; 8: 37-41
108. Han Y, Zhang J, Chen N, He L, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev 2013; Issue 3. Art. No.: CD005582. DOI: 10.1002/ 14651858.CD005582.pub4
109. Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000; 343: 1514-9
110. Tran de QH, Duong S, Bertini P, Finlayson RJ. Treatment of complex regional pain syndrome: a review of the evidence. Canadian J Anaesth 2010; 57: 149-66
111. Munts AG, van der Plas AA, Ferrari MD, Teepe-Twiss IM, Marinus J, van Hilten JJ. Efficacy and safety of a single intrathecal methylprednisolone bolus in chronic complex regional pain syndrome. Eur J Pain 2010; 14: 523-8
112. Okoro T, Tafazal SI, Longworth S, Sell PJ. Tumor necrosis alphablocking agent (etanercept): a triple blind randomized controlled trial of its use in treatment of sciatica. J Spinal Disord Tech 2010; 23: 74-7
113. Korhonen T, Karppinen J, Paimela L, et al. The treatment of disc herniation-induced sciatica with infliximab: results of a randomized, controlled, 3-month follow-up study. Spine 2005; 30: 2724-8
114. Ji RR, Xu ZZ, Strichartz G, Serhan CN. Emerging roles of resolvins in the resolution of inflammation and pain. Trends Neurosci 2011; 34: 599-609
115. Landry RP, Jacobs VL, Romero-Sandoval EA, DeLeo JA. Propentofylline, a CNS glial modulator does not decrease pain in postherpetic neuralgia patients: in vitro evidence for differential responses in human and rodent microglia and macrophages. Exp Neurol 2012; 234: 340-50
116. Anand P, Shenoy R, Palmer JE, et al. Clinical trial of the p38 MAP kinase inhibitor dilmapimod in neuropathic pain following nerve injury. Eur J Pain 2011; 15: 1040-8
117. Galli SJ, Nakae S, Tsai M. Mast cells in the development of adaptive immune responses. Nat Immunol 2005; 6: 135-42
118. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001; 413: 203-10
119. Katanosaka K, Banik RK, Giron R, Higashi T, Tominaga M, Mizumura K. Contribution of TRPV1 to the bradykinin-evoked nociceptive behavior and excitation of cutaneous sensory neurons. Neurosci Res 2008; 62: 168-75
120. Carroll MC. The complement system in regulation of adaptive immunity. Nat Immunol 2004; 5: 981-6
121. Griffin RS, Costigan M, Brenner GJ, et al. Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. J Neurosci 2007; 27: 8699-708
122. Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol 2012; 188: 21-8
123. Sun T, Yu E, Yu L, Luo J, Li H, Fu Z. LipoxinA(4) induced antinociception and decreased expression of NF-kappaB and pro-inflammatory cytokines after chronic dorsal root ganglia compression in rats. Eur J Pain 2012; 16: 18-27
124. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10: 1387-94
125. Hald A. Spinal astrogliosis in pain models: cause and effects. Cell Mol Neurobiol 2009; 29: 609-19
126. Leung L, Cahill CM. TNF-alpha and neuropathic pain-a review. J Neuroinflammation 2010; 7: 27
127. Ren K, Torres R. Role of interleukin-1beta during pain and inflammation. Brain Res Rev 2009; 60: 57-64
128. Oka T, Aou S, Hori T. Intracerebroventricular injection of interleukin-1 beta enhances nociceptive neuronal responses of the trigeminal nucleus caudalis in rats. Brain Res 1994; 656: 236-44
129. Flugel A, Hager G, Horvat A, et al. Neuronal MCP-1 expression in response to remote nerve injury. J Cereb Blood flow Metab 2001; 21: 69-76
130. Subang MC, Richardson PM. Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue. Eur J Neurosci 2001; 13: 521-8
131. Gao YJ, Zhang L, Samad OA, et al. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J Neurosci 2009; 29: 4096-108
132. Thacker MA, Clark AK, Bishop T, et al. CCL2 is a key mediator of microglia activation in neuropathic pain states. Eur J Pain 2009; 13: 263-72
133. Abbadie C, Lindia JA, Cumiskey AM, et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc Natl Acad Sci USA 2003; 100: 7947-52
134. Kiguchi N, Kobayashi Y, Kishioka S. Chemokines and cytokines in neuroinflammation leading to neuropathic pain. Curr Opin Pharmacol 2012; 12: 55-61
135. Clark AK, Yip PK, Grist J, et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci USA 2007; 104: 10655-60
136. Kawasaki Y, Xu ZZ, Wang X, et al. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med 2008; 14: 331-6
137. Shubayev VI, Angert M, Dolkas J, Campana WM, Palenscar K, Myers RR. TNFalpha-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci 2006; 31: 407-15
138. Kobayashi H, Chattopadhyay S, Kato K, et al. MMPs initiate Schwann cell-mediated MBP degradation and mechanical nociception after nerve damage. Mol Cell Neurosci 2008; 39: 619-27
139. Liuzzo JP, Petanceska SS, Devi LA. Neurotrophic factors regulate cathepsin S in macrophages and microglia: a role in the degradation of myelin basic protein and amyloid beta peptide. Mol Med 1999; 5: 334-43
140. Barclay J, Clark AK, Ganju P, et al. Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain 2007; 130: 225-34