REFERENCES
2. Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci 2012;13:859-66.
3. Sorge RE, Mapplebeck JC, Rosen S, Beggs S, Taves S, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 2015;18:1081-3.
4. Taves S, Berta T, Liu DL, Gan S, Chen G, et al. Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: Sex-dependent microglial signaling in the spinal cord. Brain Behav Immun 2016;55:70-81.
5. Mapplebeck JCS, Dalgarno R, Tu Y, Moriarty O, Beggs S, et al. Microglial P2X4R-evoked pain hypersensitivity is sexually dimorphic in rats. Pain 2018;159:1752-63.
6. Mapplebeck JC, Beggs S, Salter MW. Molecules in pain and sex: a developing story. Mol Brain 2017;10:9.
7. Grace PM, Rolan PE, Hutchinson MR. Peripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain. Brain Behav Immun 2011;25:1322-32.
8. Milligan ED, Watkins LR. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 2009;10:23-36.
9. Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 2007;10:1361-8.
10. Okamoto K, Martin DP, Schmelzer JD, Mitsui Y, Low PA. Pro- and anti-inflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain. Exp Neurol 2001;169:386-91.
11. Taskinen HS, Olsson T, Bucht A, Khademi M, Svelander L, et al. Peripheral nerve injury induces endoneurial expression of IFN-gamma, IL-10 and TNF-alpha mRNA. J Neuroimmunol 2000;102:17-25.
12. Khan J, Ramadan K, Korczeniewska O, Anwer MM, Benoliel R, et al. Interleukin-10 levels in rat models of nerve damage and neuropathic pain. Neurosci Lett 2015;592:99-106.
13. Siqueira Mietto B, Kroner A, Girolami EI, Santos-Nogueira E, Zhang J, et al. Role of IL-10 in Resolution of Inflammation and Functional Recovery after Peripheral Nerve Injury. J Neurosci 2015;35:16431-42.
14. DeLeo JA, Colburn RW, Rickman AJ. Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy. Brain Res 1997;759:50-7.
15. Raghavendra V, Tanga FY, DeLeo JA. Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci 2004;20:467-73.
16. Echeverry S, Shi XQ, Haw A, Liu H, Zhang ZW, et al. Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects. Mol Pain 2009;5:16.
17. Lee HL, Lee KM, Son SJ, Hwang SH, Cho HJ. Temporal expression of cytokines and their receptors mRNAs in a neuropathic pain model. Neuroreport 2004;15:2807-11.
18. Zhang J, Shi XQ, Echeverry S, Mogil JS, De Koninck Y, et al. Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain. J Neurosci 2007;27:12396-406.
19. 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;28:5189-94.
20. Abbadie C, Lindia JA, Cumiskey AM, Peterson LB, Mudgett JS, et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc Natl Acad Sci U S A 2003;100:7947-52.
21. Perrin FE, Lacroix S, Aviles-Trigueros M, David S. Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta in Wallerian degeneration. Brain 2005;128:854-66.
22. Jancalek R, Dubovy P, Svizenska I, Klusakova I. Bilateral changes of TNF-alpha and IL-10 protein in the lumbar and cervical dorsal root ganglia following a unilateral chronic constriction injury of the sciatic nerve. J Neuroinflammation 2010;7:11.
23. Ohtori S, Takahashi K, Moriya H, Myers RR. TNF-alpha and TNF-alpha receptor type 1 upregulation in glia and neurons after peripheral nerve injury: studies in murine DRG and spinal cord. Spine (Phila Pa 1976) 2004;29:1082-8.
24. Uceyler N, Tscharke A, Sommer C. Early cytokine expression in mouse sciatic nerve after chronic constriction nerve injury depends on calpain. Brain Behav Immun 2007;21:553-60.
25. Sorge RE, LaCroix-Fralish ML, Tuttle AH, Sotocinal SG, Austin JS, et al. Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J Neurosci 2011;31:15450-4.
26. Chen G, Luo X, Qadri MY, Berta T, Ji RR. Sex-Dependent Glial Signaling in Pathological Pain: Distinct Roles of Spinal Microglia and Astrocytes. Neurosci Bull 2018;34:98-108.
27. Lopes DM, Malek N, Edye M, Jager SB, McMurray S, et al. Sex differences in peripheral not central immune responses to pain-inducing injury. Sci Rep 2017;7:16460.
28. Stephens KE, Zhou W, Ji Z, Chen Z, He S, et al. Sex differences in gene regulation in the dorsal root ganglion after nerve injury. BMC Genomics 2019;20:147.
29. Cao L, Beaulac H, Eurich A. Differential lumbar spinal cord responses among wild type, CD4 knockout, and CD40 knockout mice in spinal nerve L5 transection-induced neuropathic pain. Mol Pain 2012;8:88.
30. Draleau K, Maddula S, Slaiby A, Nutile-McMenemy N, De Leo J, et al. Phenotypic Identification of Spinal Cord-Infiltrating CD4(+) T Lymphocytes in a Murine Model of Neuropathic Pain. J Pain Relief 2014;Suppl 3:003.
31. Costigan M, Moss A, Latremoliere A, Johnston C, Verma-Gandhu M, 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.
32. Sun C, Zhang J, Chen L, Liu T, Xu G, et al. IL-17 contributed to the neuropathic pain following peripheral nerve injury by promoting astrocyte proliferation and secretion of proinflammatory cytokines. Mol Med Rep 2017;15:89-96.
33. Kleinschnitz C, Hofstetter HH, Meuth SG, Braeuninger S, Sommer C, et al. T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression. Exp Neurol 2006;200:480-5.
34. Kim CF, Moalem-Taylor G. Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice. J Pain 2011;12:370-83.
35. Austin PJ, Kim CF, Perera CJ, Moalem-Taylor G. Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis. Pain 2012;153:1916-31.
36. Hu P, McLachlan EM. Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve lesions in the rat. Neuroscience 2002;112:23-38.
37. Evans R, Patzak I, Svensson L, De Filippo K, Jones K, et al. Integrins in immunity. J Cell Sci 2009;122:215-25.
38. Emoto M, Emoto Y, Brinkmann V, Miyamoto M, Yoshizawa I, et al. Increased resistance of LFA-1-deficient mice to lipopolysaccharide-induced shock/liver injury in the presence of TNF-alpha and IL-12 is mediated by IL-10: a novel role for LFA-1 in the regulation of the proinflammatory and anti-inflammatory cytokine balance. J Immunol 2003;171:584-93.
39. Wang Y, Kai H, Chang F, Shibata K, Tahara-Hanaoka S, et al. A critical role of LFA-1 in the development of Th17 cells and induction of experimental autoimmune encephalomyelytis. Biochem Biophys Res Commun 2007;353:857-62.
40. Wang JG, Collinge M, Ramgolam V, Ayalon O, Fan XC, et al. LFA-1-dependent HuR nuclear export and cytokine mRNA stabilization in T cell activation. J Immunol 2006;176:2105-13.
42. Lam NCK, Ornatowski W, Alberti LB, Wilkerson JL, Moezzi D, et al. .
43. Suzuki J, Yamasaki S, Wu J, Koretzky GA, Saito T. The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation. Blood 2007;109:168-75.
44. Woska JR, Jr., Shih D, Taqueti VR, Hogg N, Kelly TA, et al. A small-molecule antagonist of LFA-1 blocks a conformational change important for LFA-1 function. J Leukoc Biol 2001;70:329-34.
45. Kelly TA, Jeanfavre DD, McNeil DW, Woska JR, Jr, Reilly PL, et al. Cutting edge: a small molecule antagonist of LFA-1-mediated cell adhesion. J Immunol 1999;163:5173-7.
46. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107.
47. Vanderwall AG, Noor S, Sun MS, Sanchez JE, Yang XO, et al. Effects of spinal non-viral interleukin-10 gene therapy formulated with d-mannose in neuropathic interleukin-10 deficient mice: Behavioral characterization, mRNA and protein analysis in pain relevant tissues. Brain Behav Immun 2018;69:91-112.
48. Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014;13:924-35.
49. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994;53:55-63.
50. Milligan ED, Mehmert KK, Hinde JL, Harvey LO, Martin D, et al. Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120. Brain Res 2000;861:105-16.
51. Noor S, Sanchez JJ, Vanderwall AG, Sun MS, Maxwell JR, et al. Prenatal alcohol exposure potentiates chronic neuropathic pain, spinal glial and immune cell activation and alters sciatic nerve and DRG cytokine levels. Brain Behav Immun 2017;61:80-95.
52. Giblin PA, Lemieux RM. LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics. Curr Pharm Des 2006;12:2771-95.
53. Woska JR, Jr., Last-Barney K, Rothlein R, Kroe RR, Reilly PL, et al. Small molecule LFA-1 antagonists compete with an anti-LFA-1 monoclonal antibody for binding to the CD11a I domain: development of a flow-cytometry-based receptor occupancy assay. J Immunol Methods 2003;277:101-15.
54. Hosseini BH, Louban I, Djandji D, Wabnitz GH, Deeg J, et al. Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy. Proc Natl Acad Sci U S A 2009;106:17852-7.
55. Mellios N, Woodson J, Garcia RI, Crawford B, Sharma J, et al. beta2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A 2014;111:9947-52.
56. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25:402-8.
57. Teh PP, Vasanthakumar A, Kallies A. Development and Function of Effector Regulatory T Cells. Prog Mol Biol Transl Sci 2015;136:155-74.
59. Li X, Zheng Y. Regulatory T cell identity: formation and maintenance. Trends Immunol 2015;36:344-53.
60. Martinez GJ, Nurieva RI, Yang XO, Dong C. Regulation and function of proinflammatory TH17 cells. Ann N Y Acad Sci 2008;1143:188-211.
61. Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, et al. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A 2016;113:E1738-46.
62. Maxwell JR, Denson JL, Joste NE, Robinson S, Jantzie LL. Combined in utero hypoxia-ischemia and lipopolysaccharide administration in rats induces chorioamnionitis and a fetal inflammatory response syndrome. Placenta 2015;36:1378-84.
63. Yellowhair TR, Noor S, Maxwell JR, Anstine CV, Oppong AY, et al. Preclinical chorioamnionitis dysregulates CXCL1/CXCR2 signaling throughout the placental-fetal-brain axis. Exp Neurol 2018;301:110-9.
64. Fantini MC, Dominitzki S, Rizzo A, Neurath MF, Becker C. In vitro generation of CD4+ CD25+ regulatory cells from murine naive T cells. Nat Protoc 2007;2:1789-94.
65. Yosef N, Shalek AK, Gaublomme JT, Jin H, Lee Y, et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature 2013;496:461-8.
66. Lim MA, Lee J, Park JS, Jhun JY, Moon YM, et al. Increased Th17 differentiation in aged mice is significantly associated with high IL-1beta level and low IL-2 expression. Exp Gerontol 2014;49:55-62.
67. Sallin MA, Sakai S, Kauffman KD, Young HA, Zhu J, et al. Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis. Cell Rep 2017;18:3091-104.
68. Andersen P, Smedegaard B. CD4(+) T-cell subsets that mediate immunological memory to Mycobacterium tuberculosis infection in mice. Infect Immun 2000;68:621-9.
69. Li LX, McSorley SJ. B cells enhance antigen-specific CD4 T cell priming and prevent bacteria dissemination following Chlamydia muridarum genital tract infection. PLoS Pathog 2013;9:e1003707.
70. Murphy PG, Ramer MS, Borthwick L, Gauldie J, Richardson PM, et al. Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice. Eur J Neurosci 1999;11:2243-53.
71. Shimoyama M, Tanaka K, Hasue F, Shimoyama N. A mouse model of neuropathic cancer pain. Pain 2002;99:167-74.
73. Spataro LE, Sloane EM, Milligan ED, Wieseler-Frank J, Schoeniger D, et al. Spinal gap junctions: potential involvement in pain facilitation. J Pain 2004;5:392-405.
74. Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, et al. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci 2008;28:20-9.
75. Milligan ED, Sloane EM, Langer SJ, Hughes TS, Jekich BM, et al. Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Pain 2006;126:294-308.
76. Grace PM, Hutchinson MR, Manavis J, Somogyi AA, Rolan PE. A novel animal model of graded neuropathic pain: utility to investigate mechanisms of population heterogeneity. J Neurosci Methods 2010;193:47-53.
77. Huang D, Yu B. The mirror-image pain: an unclered phenomenon and its possible mechanism. Neurosci Biobehav Rev 2010;34:528-32.
78. Kleinschnitz C, Brinkhoff J, Zelenka M, Sommer C, Stoll G. The extent of cytokine induction in peripheral nerve lesions depends on the mode of injury and NMDA receptor signaling. J Neuroimmunol 2004;149:77-83.
79. Milligan ED, O’Connor KA, Nguyen KT, Armstrong CB, Twining C, et al. Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines. J Neurosci 2001;21:2808-19.
80. Koltzenburg M, Wall PD, McMahon SB. Does the right side know what the left is doing? Trends Neurosci 1999;22:122-7.
81. Ruohonen S, Jagodi M, Khademi M, Taskinen HS, Ojala P, et al. Contralateral non-operated nerve to transected rat sciatic nerve shows increased expression of IL-1beta, TGF-beta1, TNF-alpha, and IL-10. J Neuroimmunol 2002;132:11-7.
82. Wan YY, Flavell RA. TGF-beta and regulatory T cell in immunity and autoimmunity. J Clin Immunol 2008;28:647-59.
83. Zheng Y, Sun L, Jiang T, Zhang D, He D, et al. TNFalpha promotes Th17 cell differentiation through IL-6 and IL-1beta produced by monocytes in rheumatoid arthritis. J Immunol Res 2014;2014:2014:385352.
84. Garrison CJ, Dougherty PM, Kajander KC, Carlton SM. Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res 1991;565:1-7.
85. Jiang W, Gilkeson G. Sex Differences in monocytes and TLR4 associated immune responses; implications for systemic lupus erythematosus (SLE). J Immunother Appl 2014;1:1.
86. Schwarz JM, Bilbo SD. Sex, glia, and development: interactions in health and disease. Horm Behav 2012;62:243-53.
87. McClelland EE, Smith JM. Gender specific differences in the immune response to infection. Arch Immunol Ther Exp (Warsz) 2011;59:203-13.
88. Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol 2014;35:347-69.
89. Hewagama A, Patel D, Yarlagadda S, Strickland FM, Richardson BC. Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes Immun 2009;10:509-16.
90. Weinstein Y, Ran S, Segal S. Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. J Immunol 1984;132:656-61.
91. Padi SS, Shi XQ, Zhao YQ, Ruff MR, Baichoo N, et al. Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation. Pain 2012;153:95-106.
92. White FA, Bhangoo SK, Miller RJ. Chemokines: integrators of pain and inflammation. Nat Rev Drug Discov 2005;4:834-44.
93. Wilkerson JL, Gentry KR, Dengler EC, Wallace JA, Kerwin AA, et al. Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti-inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia. Brain Behav 2012;2:155-77.
94. Wilkerson JL, Gentry KR, Dengler EC, Wallace JA, Kerwin AA, et al. Intrathecal cannabilactone CB(2)R agonist, AM1710, controls pathological pain and restores basal cytokine levels. Pain 2012;153:1091-106.
95. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008;172:146-55.
96. Li GZ, Zhong D, Yang LM, Sun B, Zhong ZH, et al. Expression of interleukin-17 in ischemic brain tissue. Scand J Immunol 2005;62:481-6.
97. Senba E, Okamoto K, Imbe H. New Insights into Fibromyalgia. Chaper 2: Central sensitization and descending facilitation in chronic pain state. Published by InTech; 2012.
99. Xu D, Zhao H, Gao H, Zhao H, Liu D, et al. Participation of pro-inflammatory cytokines in neuropathic pain evoked by chemotherapeutic oxaliplatin via central GABAergic pathway. Mol Pain 2018;14:1744806918783535.
100. Noor S, Sanchez JJ, Pervin Z, Sanchez JE, Sun MS, et al. Neuropathic pain susceptibility in prenatal alcohol exposed (PAE) females is mediated by the proinflammatory actions of lymphocyte function-associated antigen (LFA)-1 on immune and glial cells. Peripheral Mechanisms of Neuropathic Pain, Neuroscience Meeting Planner, San Diego, CA, Society for Neuroscience, 2018.
101. Prajeeth CK, Kronisch J, Khorooshi R, Knier B, Toft-Hansen H, et al. Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties. J Neuroinflammation 2017;14:204.
102. Xie L, Yang SH. Interaction of astrocytes and T cells in physiological and pathological conditions. Brain Res 2015;1623:63-73.
103. Beurel E, Harrington LE, Buchser W, Lemmon V, Jope RS. Astrocytes modulate the polarization of CD4+ T cells to Th1 cells. PLoS One 2014;9:e86257.
104. Sonar SA, Lal G. Differentiation and Transmigration of CD4 T Cells in Neuroinflammation and Autoimmunity. Front Immunol 2017;8:1695.
105. Engelhardt B. Molecular mechanisms involved in T cell migration across the blood-brain barrier. J Neural Transm (Vienna) 2006;113:477-85.
106. Verhagen J, Wraith DC. Blockade of LFA-1 augments in vitro differentiation of antigen-induced Foxp3(+) Treg cells. J Immunol Methods 2014;414:58-64.
107. Sanchez JJ, Sanchez JE, Noor S, Ruffaner-Hanson CD, Davies S, et al. Targeting the beta2-integrin LFA-1, reduces adverse neuroimmune actions in neuropathic susceptibility caused by prenatal alcohol exposure. Acta Neuropathol Commun 2019;7:54.
