Can modulating inflammatory response be a good strategy to treat neuropathic pain?

Current Pharmaceutical Design

Volumn 21, Issue 7, 2015, Pages 831-839

  Zhang, Ji ^a,b   Echeverry, Stefania ^a,b   Lim, Tony K Y ^a,b   Lee, Seung Hwan ^a   Shi, Xiang Qun ^a   Huang, Hao ^a  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

Chemokines; Cytokines; Endothelial cells; Glia; Immune cells; Nerve injury; Pain; Treatment

Indexed keywords

CHEMOKINE; CYTOKINE; ANTIINFLAMMATORY AGENT; AUTACOID;

ARTICLE; CHRONIC PAIN; ENDOTHELIUM CELL; HOMEOSTASIS; HUMAN; IMMUNOCOMPETENT CELL; INFLAMMATION; NERVE FIBER; NERVE INJURY; NEUROPATHIC PAIN; NONHUMAN; PRIORITY JOURNAL; SENSITIZATION; ANALGESIA; ANIMAL; ANTAGONISTS AND INHIBITORS; IMMUNOLOGY; METABOLISM; NEURALGIA; PROCEDURES; RANDOMIZED CONTROLLED TRIAL (TOPIC); TRENDS;

ANIMALS; ANTI-INFLAMMATORY AGENTS; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; NEURALGIA; PAIN MANAGEMENT; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84925848044     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612820666141027115508     Document Type: Article

References (112)

1. [1] Todd KH, Ducharme J, Choiniere M, et al. Pain in the emergency department: results of the pain and emergency medicine initiative (PEMI) multicenter study. J Pain 2007; 8(6): 460-6.
2. [2] Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bouhassira D. Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion? Pain 2008; 138(2): 343-53.
3. [3] Finnerup NB, Sindrup SH, Jensen TS. Recent advances in pharmacological treatment of neuropathic pain. F1000 Med Rep 2010; 2: 52.
4. [4] Dworkin RH, O'Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007; 132(3): 237-51.
5. [5] Sindrup SH, Finnerup NB, Jensen TS. Tailored treatment of peripheral neuropathic pain. Pain 2012; 153(9): 1781-2.
6. [6] Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 2007; 10(11): 1361-8.
7. [7] Olsson Y. Microenvironment of the peripheral nervous system under normal and pathological conditions. Crit Rev Neurobiol 1990; 5(3): 265-311.
8. [8] Perkins NM, Tracey DJ. Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 2000; 101(3): 745-57.
9. [9] 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(35): 12533-42.
10. [10] Schafers M, Lee DH, Brors D, Yaksh TL, Sorkin LS. Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation. J Neurosci 2003; 23(7): 3028-38.
11. [11] Scapini P, Lapinet-Vera JA, Gasperini S, Calzetti F, Bazzoni F, Cassatella MA. The neutrophil as a cellular source of chemokines. Immunol Rev 2000; 177: 195-203.
12. [12] Mueller M, Leonhard C, Wacker K, et al. Macrophage response to peripheral nerve injury: the quantitative contribution of resident and hematogenous macrophages. Lab Invest 2003; 83(2): 175-85.
13. [13] Vass K, Hickey WF, Schmidt RE, Lassmann H. Bone marrowderived elements in the peripheral nervous system. An immunohistochemical and ultrastructural investigation in chimeric rats. Lab Invest 1993; 69(3): 275-82.
14. [14] Gaudet AD, Popovich PG, Ramer MS. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammation 2011; 8: 110.
15. [15] Rotshenker S. Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 2011; 8: 109.
16. [16] Sommer C, Schafers M. Painful mononeuropathy in C57BL/Wld mice with delayed wallerian degeneration: differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity. Brain Res 1998; 784(1-2): 154-62.
17. [17] Myers RR, Heckman HM, Rodriguez M. Reduced hyperalgesia in nerve-injured WLD mice: relationship to nerve fiber phagocytosis, axonal degeneration, and regeneration in normal mice. Exp Neurol 1996; 141(1): 94-101.
18. [18] Liu T, van Rooijen N, Tracey DJ. Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain 2000; 86(1-2): 25-32.
19. [19] Mert T, Gunay I, Ocal I, et al. Macrophage depletion delays progression of neuropathic pain in diabetic animals. Naunyn Schmiedebergs Arch Pharmacol 2009; 379(5): 445-52.
20. [20] Barclay J, Clark AK, Ganju P, et al. Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain 2007; 130(3): 225-34.
21. [21] Rutkowski MD, Pahl JL, Sweitzer S, van Rooijen N, DeLeo JA. Limited role of macrophages in generation of nerve injury-induced mechanical allodynia. Physiol Behav 2000; 71(3-4): 225-35.
22. [22] Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8(12): 958-69.
23. [23] Lee S, Zhang J. Heterogeneity of macrophages in injured trigeminal nerves: Cytokine/chemokine expressing vs. phagocytic macrophages. Brain Behav Immun 2012; 26(6): 891-903.
24. [24] Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990; 43(2): 205-18.
25. [25] Echeverry S, Wu Y, Zhang J. Selectively reducing cytokine/chemokine expressing macrophages in injured nerves impairs the development of neuropathic pain. Exp Neurol 2013; 240: 205-18.
26. [26] Moalem G, Xu K, Yu L. T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience 2004; 129(3): 767-77.
27. [27] Armati PJ, Mathey EK. An update on Schwann cell biology--immunomodulation, neural regulation and other surprises. J Neurol Sci 2013; 333(1-2): 68-72.
28. [28] Ydens E, Lornet G, Smits V, Goethals S, Timmerman V, Janssens S. The neuroinflammatory role of Schwann cells in disease. Neurobiol Dis 2013; 55: 95-103.
29. [29] Meyer zu HG, Zozulya AL, El-Haddad H, et al. Active immunization induces toxicity of diphtheria toxin in diphtheria resistant mice--implications for neuroinflammatory models. J Immunol Methods 2010; 354(1-2): 80-4.
30. [30] Liu H, Shiryaev SA, Chernov AV, et al. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain. J Neuroinflammation 2012; 9: 119.
31. [31] Marinelli S, Nazio F, Tinari A, et al. Schwann cell autophagy counteracts the onset and chronification of neuropathic pain. Pain 2014; 155(1): 93-107.
32. [32] Zhou XF, Deng YS, Chie E, et al. Satellite-cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat. Eur J Neurosci 1999; 11(5): 1711-22.
33. [33] Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett 2004; 361(1-3): 184-7.
34. [34] Zelenka M, Schafers M, Sommer C. Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain 2005; 116(3): 257-63.
35. [35] Schafers M, Geis C, Svensson CI, Luo ZD, Sommer C. Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur J Neurosci 2003; 17(4): 791-804.
36. [36] Shubayev VI, Myers RR. Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors. J Neuroimmunol 2001; 114(1-2): 48-56.
37. [37] Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 1997; 81(1): 255-62.
38. [38] Junger H, Sorkin LS. Nociceptive and inflammatory effects of subcutaneous TNFalpha. Pain 2000; 85(1-2): 145-51.
39. [39] Wagner R, Myers RR. Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport 1996; 7(18): 2897-901.
40. [40] Wolf G, Gabay E, Tal M, Yirmiya R, Shavit Y. Genetic impairment of interleukin-1 signaling attenuates neuropathic pain, autotomy, and spontaneous ectopic neuronal activity, following nerve injury in mice. Pain 2006; 120(3): 315-24.
41. [41] Schafers M, Sorkin L. Effect of cytokines on neuronal excitability. Neurosci Lett 2008; 437(3): 188-93.
42. [42] Cunha TM, Verri WA, Jr., Silva JS, Poole S, Cunha FQ, Ferreira SH. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc Natl Acad Sci USA 2005; 102(5): 1755-60.
43. [43] Keswani SC, Polley M, Pardo CA, Griffin JW, McArthur JC, Hoke A. Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons. Ann Neurol 2003; 54(3): 287-96.
44. [44] Zhang J, Shi XQ, Echeverry S, Mogil JS, De Koninck Y, Rivest S. Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain. J Neurosci 2007; 27(45): 12396-406.
45. [45] Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10(11): 1387-94.
46. [46] Gehrmann J, Matsumoto Y, Kreutzberg GW. Microglia: intrinsic immuneffector cell of the brain. Brain Res Brain Res Rev 1995; 20(3): 269-87.
47. [47] 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(2): 289-304.
48. [48] Fu KY, Light AR, Matsushima GK, Maixner W. Microglial reactions after subcutaneous formalin injection into the rat hind paw. Brain Res 1999; 825(1-2): 59-67.
49. [49] Zhang J, Hoffert C, Vu HK, Groblewski T, Ahmad S, O'Donnell D. Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur J Neurosci 2003; 17(12): 2750-4.
50. [50] Hashizume H, DeLeo JA, Colburn RW, Weinstein JN. Spinal glial activation and cytokine expression after lumbar root injury in the rat. Spine 2000; 25(10): 1206-17.
51. [51] 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(25): 10655-60.
52. [52] Watkins LR, Milligan ED, Maier SF. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol 2003; 521: 1-21.
53. [53] 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 factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 2008; 28(20): 5189-94.
54. [54] Coull JA, Beggs S, Boudreau D, et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005; 438(7070): 1017-21.
55. [55] Hua XY, Svensson CI, Matsui T, Fitzsimmons B, Yaksh TL, Webb M. Intrathecal minocycline attenuates peripheral inflammationinduced hyperalgesia by inhibiting p38 MAPK in spinal microglia. Eur J Neurosci 2005; 22(10): 2431-40.
56. [56] Milligan ED, Twining C, Chacur M, et al. Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci 2003; 23(3): 1026-40.
57. [57] 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(2): 624-30.
58. [58] Tsuda M, Shigemoto-Mogami Y, Koizumi S, et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 2003; 424(6950): 778-83.
59. [59] Beggs S, Salter MW. Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury. Brain Behav Immun 2006 Dec 16.
60. [60] 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(1): 130-42.
61. [61] Thacker M, Moseley GL, Flor H. Neuropathic pain. Management is more than pills. BMJ 2009; 339: b3502.
62. [62] Zhang J, De Koninck Y. Spatial and temporal relationship between monocyte chemoattractant protein-1 expression and spinal glial activation following peripheral nerve injury. J Neurochem 2006; 97(3): 772-83.
63. [63] Clark AK, Yip PK, Malcangio M. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci 2009; 29(21): 6945-54.
64. [64] Verge GM, Milligan ED, Maier SF, Watkins LR, Naeve GS, Foster AC. Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur J Neurosci 2004; 20(5): 1150-60.
65. [65] 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(13): 7947-52.
66. [66] Chapman GA, Moores KE, Gohil J, et al. The role of fractalkine in the recruitment of monocytes to the endothelium. Eur J Pharmacol 2000; 392(3): 189-95.
67. [67] Milligan ED, Zapata V, Chacur M, et al. Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats. Eur J Neurosci 2004; 20(9): 2294-302.
68. [68] Tsuda M, Inoue K. [Neuropathic pain and ATP receptors in spinal microglia]. Brain Nerve 2007; 59(9): 953-9.
69. [69] Salter MW, De KY, Henry JL. Physiological roles for adenosine and ATP in synaptic transmission in the spinal dorsal horn. Prog Neurobiol 1993; 41(2): 125-56.
70. [70] Soeda H, Tatsumi H, Katayama Y. Neurotransmitter release from growth cones of rat dorsal root ganglion neurons in culture. Neuroscience 1997; 77(4): 1187-99.
71. [71] Clark AK, Staniland AA, Marchand F, Kaan TK, McMahon SB, Malcangio M. P2X7-dependent release of interleukin-1beta and nociception in the spinal cord following lipopolysaccharide. J Neurosci 2010; 30(2): 573-82.
72. [72] Kobayashi K, Takahashi E, Miyagawa Y, Yamanaka H, Noguchi K. Induction of the P2X7 receptor in spinal microglia in a neuropathic pain model. Neurosci Lett 2011; 504(1): 57-61.
73. [73] Haynes SE, Hollopeter G, Yang G, et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 2006; 9(12): 1512-9.
74. [74] Katagiri A, Shinoda M, Honda K, Toyofuku A, Sessle BJ, Iwata K. Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats. Mol Pain 2012; 8: 23.
75. [75] Kobayashi K, Yamanaka H, Fukuoka T, Dai Y, Obata K, Noguchi K. P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain. J Neurosci 2008; 28(11): 2892-902.
76. [76] Maragakis NJ, Rothstein JD. Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2006; 2(12): 679-89.
77. [77] Miyoshi K, Obata K, Kondo T, Okamura H, Noguchi K. Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury. J Neurosci 2008; 28(48): 12775-87.
78. [78] Zhuang ZY, Gerner P, Woolf CJ, Ji RR. ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 2005; 114(1-2): 149-59.
79. [79] Zhuang ZY, Wen YR, Zhang DR, et al. A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance. J Neurosci 2006; 26(13): 3551-60.
80. [80] 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(3): 331-6.
81. [81] Cao L, DeLeo JA. CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur J Immunol 2008; 38(2): 448-58.
82. [82] 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(46): 14415-22.
83. [83] 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(30): 10819-28.
84. [84] Sweitzer SM, Hickey WF, Rutkowski MD, Pahl JL, DeLeo JA. Focal peripheral nerve injury induces leukocyte trafficking into the central nervous system: potential relationship to neuropathic pain. Pain 2002; 100(1-2): 163-70.
85. [85] Kleinschnitz C, Hofstetter HH, Meuth SG, Braeuninger S, Sommer C, Stoll G. T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression. Exp Neurol 2006; 200(2): 480-5.
86. [86] 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(19): 8032-7.
87. [87] Kim CF, Moalem-Taylor G. Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice. J Pain 2011; 12(3): 370-83.
88. [88] Gordh T, Chu H, Sharma HS. Spinal nerve lesion alters bloodspinal cord barrier function and activates astrocytes in the rat. Pain 2006; 124(1-2): 211-21.
89. [89] 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.
90. Kanda T. [Blood-nerve barrier: structure and function]. Brain Nerve 2011; 63(6): 557-69.
91. [91] Seitz RJ, Reiners K, Himmelmann F, Heininger K, Hartung HP, Toyka KV. The blood-nerve barrier in Wallerian degeneration: a sequential long-term study. Muscle Nerve 1989; 12(8): 627-35.
92. [92] Omura K, Ohbayashi M, Sano M, Omura T, Hasegawa T, Nagano A. The recovery of blood-nerve barrier in crush nerve injury--a quantitative analysis utilizing immunohistochemistry. Brain Res 2004; 1001(1-2): 13-21.
93. [93] Lim TK, Shi XQ, Martin HC, Huang H, Luheshi G, Rivest S, et al. Blood-nerve barrier dysfunction contributes to the generation of neuropathic pain and allows targeting of injured nerves for pain relief. Pain 2014; 155(5): 954-67.
94. [94] McMahon SB, Cafferty WB, Marchand F. Immune and glial cell factors as pain mediators and modulators. Exp Neurol 2005; 192(2): 444-62.
95. [95] Coyle DE. Partial peripheral nerve injury leads to activation of astroglia and microglia which parallels the development of allodynic behavior. Glia 1998; 23(1): 75-83.
96. [96] Serhan CN, Brain SD, Buckley CD, et al. Resolution of inflammation: state of the art, definitions and terms. FASEB J 2007; 21(2): 325-32.
97. [97] Tramullas M, Lantero A, Diaz A, et al. BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) reveals the involvement of the transforming growth factor-beta family in pain modulation. J Neurosci 2010; 30(4): 1502-11.
98. [98] Abraham KE, McMillen D, Brewer KL. The effects of endogenous interleukin-10 on gray matter damage and the development of pain behaviors following excitotoxic spinal cord injury in the mouse. Neuroscience 2004; 124(4): 945-52.
99. [99] Romero-Sandoval A, Nutile-McMenemy N, DeLeo JA. Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury. Anesthesiology 2008; 108(4): 722-34.
100. [100] Guasti L, Richardson D, Jhaveri M, et al. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol Pain 2009; 5: 35.
101. [101] Soderquist RG, Sloane EM, Loram LC, et al. Release of plasmid DNA-encoding IL-10 from PLGA microparticles facilitates longterm reversal of neuropathic pain following a single intrathecal administration. Pharm Res 2010; 27(5): 841-54.
102. [102] Calvo M, Dawes JM, Bennett DL. The role of the immune system in the generation of neuropathic pain. Lancet Neurol 2012; 11(7): 629-42.
103. [103] Kerschensteiner M, Gallmeier E, Behrens L, et al. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 1999; 189(5): 865-70.
104. [104] Kiefer R, Kieseier BC, Stoll G, Hartung HP. The role of macrophages in immune-mediated damage to the peripheral nervous system. Prog Neurobiol 2001; 64(2): 109-27.
105. [105] Machelska H. Dual peripheral actions of immune cells in neuropathic pain. Arch Immunol Ther Exp (Warsz) 2011; 59(1): 11-24.
106. [106] Labuz D, Schmidt Y, Schreiter A, Rittner HL, Mousa SA, Machelska H. Immune cell-derived opioids protect against neuropathic pain in mice. J Clin Invest 2009; 119(2): 278-86.
107. [107] Uceyler N, Rogausch JP, Toyka KV, Sommer C. Differential expression of cytokines in painful and painless neuropathies. Neurology 2007; 69(1): 42-9.
108. [108] Ludwig J, Binder A, Steinmann J, Wasner G, Baron R. Cytokine expression in serum and cerebrospinal fluid in non-inflammatory polyneuropathies. J Neurol Neurosurg Psychiatry 2008; 79(11): 1268-73.
109. [109] Banati RB. Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation? J Physiol Paris 2002; 96(3-4): 289-99.
110. [110] Del VL, Schwartzman RJ, Alexander G. Spinal cord histopathological alterations in a patient with longstanding complex regional pain syndrome. Brain Behav Immun 2009; 23(1): 85-91.
111. [111] Shi Y, Gelman BB, Lisinicchia JG, Tang SJ. Chronic-painassociated astrocytic reaction in the spinal cord dorsal horn of human immunodeficiency virus-infected patients. J Neurosci 2012; 32(32): 10833-40.
112. [112] Landry RP, Jacobs VL, Romero-Sandoval EA, DeLeo JA. Propentofylline, a CNS glial modulator does not decrease pain in post-herpetic neuralgia patients: in vitro evidence for differential responses in human and rodent microglia and macrophages. Exp Neurol 2012; 234(2): 340-50.