Role of the immune system in chronic pain

Nature Reviews Neuroscience

Volumn 6, Issue 7, 2005, Pages 521-532

  Marchand, Fabien ^a   Perretti, Mauro ^b   McMahon, Stephen B ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CENTRAL NERVOUS SYSTEM; CHRONIC PAIN; HUMAN; HYPERALGESIA; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; INFLAMMATION; MEDIATOR RELEASE; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; PERIPHERAL NERVE INJURY; PRIORITY JOURNAL; RAT; REVIEW;

ANIMALS; ANNEXIN A1; CHRONIC DISEASE; HUMANS; IMMUNE SYSTEM; MODELS, BIOLOGICAL; NOCICEPTORS; PAIN; RECEPTORS, FORMYL PEPTIDE; RECEPTORS, LIPOXIN;

EID: 21744433587     PISSN: 1471003X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrn1700     Document Type: Review

References (153)

1. Numazaki, M. & Tominaga M. Nociception and TRP Channels. Curr. Drug Targets CNS Neurol. Disord. 3, 479-485 (2004).
2. Lewin, G. R. & Moshourab, R. Mechanosensation and pain. J. Neurobiol. 61, 30-44 (2004).
3. Cook, S. P. Vulchanova, L., Hargreaves, K. M., Elde, R. & McCleskey, E. W. Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature 387, 505-508 (1997).
4. Stassen, M., Hultner, L. & Schmitt, E. Classical and alternative pathways of mast cell activation. Crit. Rev. Immunol. 22, 115-140 (2002).
5. Drummond, P. D. The effect of cutaneous mast cell degranulation on sensitivity to heat. Inflamm. Res. 53, 309-315 (2004).
6. Parada, C. A., Tambeli, C. H., Cunha, F. Q. & Ferreira, S. H. The major role of peripheral release of histamine and 5-hydroxytryptamine in formalin-induced nociception. Neuroscience 102, 937-944 (2001).
7. Ribeiro, R. A. et al. Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice. Eur. J. Pharmacol. 387, 111-118 (2000).
8. Hoogerwerf, W. A. et al. The role of mast cells in the pathogenesis of pain in chronic pancreatitis. BMC Gastroenterol. 5, 8 (2005).
9. Piovezan, A. P. et al. Endothelins contribute towards nociception induced by antigen in ovalbumin-sensitised mice. Br. J. Pharmacol. 141, 755-763 (2004).
10. Oberpenning, F., van Ophoven, A. & Hertle, L. Interstitial cystitis: an update. Curr. Opin. Urol. 12, 321-332 (2002).
11. Thomazzi, S. M., Ribeiro, R. A., Campos D. I., Cunha, F. Q. & Ferreira, S. H. Tumor necrosis factor, interleukin-1 and interleukin-8 mediate the nociceptive activity of supernatant of LPS-stimulated macrophages. Mediators Inflamm. 6, 195-200 (1997).
12. Souza, G. E., Cunha, F. Q., Melb, R. & Ferreira, S. H. Neutrophil migration induced by inflammatory stimuli is reduced by macrophage depletion. Agents Actions 24, 377-380 (1988).
13. Brack, A. & Stein, C. Potential links between leukocytes and antinociception. Pain 111, 1-2 (2004).
14. Heuft, H. G., Goudeva, L. & Blasczyk, R. A comparative study of adverse reactions occurring after administration of glycosylated granulocyte colony stimulating factor and/or dexamethasone for mobilization of neutrophils in healthy donors. Ann. Hematol. 83, 279-285 (2004).
15. Chou, T. C., Chang, L. P., Li, C. Y., Wong, C. S. & Yang, S. P. The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia. Anesth. Analg. 97, 1724-1729 (2003).
16. McMahon, S. B., Cafferty, W. B. & Marchand, F. Immune and glial cell factors as pain mediators and modulators. Exp. Neurol. 192, 444-462 (2005). This article reviews immune and glial components of experimental pain, highlighting the actions of some of the key immune-derived mediators and modulators of pain transmission.
17. Bennett, G., al Rashed, S., Hoult, J. R. & Brain, S. D. Nerve growth factor induced hyperalgesia in the rat hind paw is dependent on circulating neutrophils. Pain 77, 315-322 (1998).
18. Farquhar-Smith, W. P. & Rice, A. S. A novel neuroimmune mechanism in cannabinoid-mediated attenuation of nerve growth factor-induced hyperalgesia. Anesthesiology 99, 1391-1401 (2003).
19. Sibilia, J. Novel concepts and treatments for autoimmune disease: ten focal points. Joint Bone Spine 71, 511-517 (2004).
20. McMahon, S. B., Bennett, D. L. H. & Bevan S. in Textbook of Pain (eds McMahon, S. B. & Koltzenburg, M.) Chapter 3 (Elsevier, London, in the press)
21. Omote, K. et al. Peripheral nitric oxide in carrageenan-induced inflammation. Brain Res. 912, 171-175 (2001).
22. Thomsen, L. L. & Diesen, J. Nitric oxide in primary headaches. Curr. Opin. Neurol. 14, 315-321 (2001).
23. Aley, K. O., McCarter, G. & Levine, J. D. Nitric oxide signaling in pain and nociceptor sensitization in the rat. J. Neurosci. 18, 7008-7014 (1998).
24. Hanauer, S. B. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: overview of randomized clinical studies. Rev. Gastroenterol. Disord 4 (Suppl. 3), S18-S24 (2004).
25. Roberts, L. & McColi, G. J. Tumour necrosis factor inhibitors: risks and benefits in patients with rheumatoid arthritis. Intern. Med. J. 34, 687-693 (2004).
26. Bonnington, J. K. & McNaughton, P. A. Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor. J. Physiol. (Lond.) 551, 433-446 (2003).
27. Hwang, S. W. et al. Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc. Natl Acad. Sci. USA 97, 6155-6160 (2000).
28. Noorbakhsh, F., Vergnolle, N., Hollenberg, M. D. & Power, C. Proteinase-activated receptors in the nervous system. Nature Rev. Neurosci. 4, 981-990 (2003).
29. Oh, S. B. et al. Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J. Neurosci. 21, 5027-5035 (2001). The first evidence that chemokines have a direct effect on primary nociceptive neurons, and, therefore, a potential role in pain transmission.
30. Sindrup, S. H. & Jensen, T. S. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 83, 389-400 (1999).
31. Le Bars, D., Gozariu, M. & Cadden, S. W. Animal models of nociception. Pharmacol. Rev. 53, 597-652 (2001).
32. Ossipov, M. H., Lai, J., Malan, T. P. Jr & Porreca, F. Spinal and supraspinal mechanisms of neuropathic pain. Ann. NY Acad. Sci. 909, 12-24 (2000).
33. Zuo, Y., Perkins, N. M., Tracey, D. J. & Geczy, C. L. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 105, 467-479 (2003).
34. Perkins, N. M. & Tracey, D. J. Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 101, 745-757 (2000).
35. Daemen, M. A. et al. Neurogenic inflammation in an animal model of neuropathic pain. Neurol. Res. 20, 41-45 (1998).
36. Levine, J. D., Coderre, T. J., White, D. M., Finkbeiner, W. E. & Basbaum, A. I. Denervation-induced inflammation in the rat. Neurosci. Lett. 119, 37-40 (1990).
37. Cui, J. G., Holmin, S., Mathiesen, T., Meyerson, B. A. & Linderoth, B. Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy. Pain 88, 239-248 (2000).
38. 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. 784, 154-162 (1998).
39. Myers, R. R., Heckman, H. M. & Rodriguez, M. Reduced hyperalgesia in nerve-injured WLD mice: relationship to nerve fiber phagocytosis, axonal degeneration, and regeneration in normal mice. Exp. Neurol. 141, 94-101 (1996).
40. Liu, T., van Rooijen, N. & Tracey, D. J. Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain 86, 25-32 (2000).
41. Heumann, R. et al. Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc. Natl Acad. Sci. USA 84, 8735-8739 (1987).
42. Rutkowski, M. D., Pahl, J. L., Sweitzer, S., van Rooijen, N. & DeLeo, J. A. Limited role of macrophages in generation of nerve injury-induced mechanical allodynia. Physiol. Behav. 71, 225-235 (2002).
43. Moalem, G., Xu, K. & Yu, L. T. lymphocytes play a rale in neuropathic pain following peripheral nerve injury in rats. Neuroscience 129, 767-777 (2004).
44. Tsai, Y. C., Won, S. J. & Lin, M. T. Effects of morphine on immune response in rats with sciatic constriction injury. Pain 88, 155-160 (2000).
45. Tsai, Y. C. & Won, S. J. Effects of tramadol on T lymphocyte proliferation and natural killer cell activity in rats with sciatic constriction injury. Pain 92, 63-69 (2001).
46. Lu, X. & Richardson, P. M. Responses of macrophages in rat dorsal root ganglia following peripheral nerve injury. J. Neurocytol. 22, 334-341 (1993).
47. Sommer, C. & Schroder, J. M. HLA-DR expression in peripheral neuropathies: the role of Schwann cells, resident and hematogenous macrophages, and endoneurial fibroblasts. Acta Neuropathol. (Berl.) 89, 63-71 (1995). One of the first papers to identify a role for macrophages in pain after peripheral nerve injury.
48. Hu, P. & McLachlan, E. M. Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve lesions in the rat. Neuroscience 112, 23-38 (2002).
49. Dina, O. A. et al. Integrin signaling in inflammatory and neuropathic pain in the rat. Eur. J. Neurosci. 19, 634-642 (2004).
50. Fu, W. M. et al. Inhibition of neuropathic pain by a potent disintegrin - triflavin. Neurosci. Lett. 368, 263-268 (2004).
51. Sweitzer, S. M., White, K. A., Dutta, C. & DeLeo, J. A. The differential role of spinal MHC class II and cellular adhesion molecules in peripheral inflammatory versus neuropathic pain in rodents. J. Neuroimmunol. 125, 82-93 (2002).
52. Boddeke, E. W. Involvement of chemokines in pain. Eur. J. Pharmacol. 429, 115-119 (2001). An informative review about the role of chemokines in pain.
53. George, A., Schmidt, C., Weishaupt, A., Toyka, K. V. & Sommer, C. Serial determination of tumor necrosis factor-α content in rat sciatic nerve after chronic constriction injury. Exp. Neurol. 160, 124-132 (1999).
54. Schafers, M., Svensson, C. I., Sommer, C. & Sorkin, L. S. Tumor necrosis factor-α induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons. J. Neurosci. 23, 2517-2521 (2003).
55. Schafers, M., Geis, C., Svensson, C. I., Luo, Z. D. & Sommer, C. Selective increase of tumour necrosis factor-α in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur. J. Neurosci. 17, 791-804 (2003).
56. Wagner, R. & Myers, R. R. Schwann cells produce tumor necrosis factor α: expression in injured and non-injured nerves. Neuroscience 73, 625-629 (1996).
57. Wagner, R. & Myers, R. R. Endoneurial injection of TNF-α produces neuropathic pain behaviors. Neuroreport 7, 2897-2901 (1996). A historically important article that provided some of the first evidence that TNFα might be involved in pain modulation after peripheral nerve injury.
58. Sommer, C. et al. Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy. Brain Res. 913, 86-89 (2001).
59. Sommer, C., Schafers, M., Marziniak, M. & Toyka, K. V. Etanercept reduces hyperalgesia in experimental painful neuropathy. J. Peripher. Nerv. Syst. 6, 67-72 (2001).
60. Lindenlaub, T., Teuteberg, P., Hartung, T. & Sommer, C. Effects of neutralizing antibodies to TNF-α on pain-related behavior and nerve regeneration in mice with chronic constriction injury. Brain Res. 866, 15-22 (2000).
61. Schafers, M., Brinkhoff, J., Neukirchen, S., Marziniak, M. & Sommer, C. Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-α and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice. Neurosci. Lett. 310, 113-116 (2001).
62. Sommer, C., Schmidt, C. & George, A. Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1. Exp. Neurol. 151, 138-142 (1998).
63. George, A., Buehl, A. & Sommer, C. Tumor necrosis factor receptor 1 and 2 proteins are differentially regulated during Wallerian degeneration of mouse sciatic nerve. Exp. Neurol. 192, 163-166 (2005).
64. Sommer, C., Petrausch, S., Lindenlaub, T. & Toyka, K. V. Neutralizing antibodies to interleukin 1-receptor reduce pain associated behavior in mice with experimental neuropathy. Neurosci. Lett. 270, 25-28 (1999).
65. Fukuoka, H., Kawatani, M., Hisamitsu, T. & Takeshige, C. Cutaneous hyperalgesia induced by peripheral injection of interleukin-1 β in the rat. Brain Res. 657, 133-140 (1994).
66. Obreja, O., Rathee, P. K., Lips, K. S., Distler, C. & Kress, M. IL-1 β potentiates heat-activated currents in rat sensory neurons: involvement of IL-1RI, tyrosine kinase, and protein kinase C. FASEB J. 16, 1497-1503 (2002).
67. De Jongh, R. F. et al. The role of interleukin-6 in nociception and pain. Anesth. Analg. 96, 1096-1103 (2003). This article reviews the involvement of IL-6 in pain.
68. Murphy, P. G. 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. 11, 2243-2253 (1999).
69. Ramer, M. S., Murphy, P. G., Richardson, P. M. & Bisby, M. A. Spinal nerve lesion-induced mechanoallodynia and adrenergic sprouting in sensory ganglia are attenuated in interleukin-6 knockout mice. Pain 78, 115-121 (1998).
70. 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. 48, 463-469 (2004).
71. Abbadie, C. et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc. Natl. Acad. Sci. USA 100, 7947-7952 (2003).
72. Milligan, E. D. et al. Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats. Eur. J. Neurosci. 20, 2294-2302 (2004).
73. Verge, G. M. et al. Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur. J. Neurosci. 20, 1150-1160 (2004). The first paper to show that fractalkine release by neurons could be an activator of microglia.
74. Cunha, J. M., Cunha, F. Q., Poole, S. & Ferreira, S. H. Cytokine-mediated inflammatory hyperalgesia limited by interleukin-1 receptor antagonist. Br. J. Pharmacol. 130, 1418-1424 (2000).
75. Sommer, C. & Kress, M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci. Lett. 361, 184-187 (2004). A short review on the involvement of different cytokines in inflammatory and neuropathic pain.
76. Ma, W. & Eisenach, J. C. Four PGE2 EP receptors are up-regulated in injured nerve following partial sciatic nerve ligation. Exp. Neurol. 183, 581-592 (2003).
77. Ma, W. & Eisenach, J. C. Morphological and pharmacological evidence for the role of peripheral prostaglandins in the pathogenesis of neuropathic pain. Eur. J. Neurosci. 15, 1037-1047 (2002).
78. Ma, W. & Eisenach, J. C. Intraplantar injection of a cyclooxygenase inhibitor ketorolac reduces immunoreactivities of substance P, calcitonin gene-related peptide, and dynorphin in the dorsal horn of rats with nerve injury or inflammation. Neuroscience 121, 681-690 (2003).
79. Sweitzer, S. M., Mickey, W. F., Rutkowski, M. D., Pahl, J. L. & DeLeo, J. A. Focal peripheral nerve injury induces leukocyte trafficking into the central nervous system: potential relationship to neuropathic pain. Pain 100, 163-170 (2002).
80. Rutkowski, M. D., Lambert, F., Raghavendra, V. & DeLeo, J. A. Presence of spinal B7.2 (CD86) but not B7.1 (CD80) co-stimulatory molecules following peripheral nerve injury: role of nondestructive immunity in neuropathic pain. J. Neuroimmunol. 146, 94-98 (2004).
81. De Nicola, A. F. et al. Steroid effects on glial cells: detrimental or protective for spinal cord function? Ann. NY Acad. Sci. 1007, 317-328 (2003).
82. Maller, S. T., Dykstra, C., Grzybycki, D., Murphy, S. & Gebhart, G. F. The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat Neuropharmacology 33, 1471-1478 (1994).
83. Milligan, E. 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. 861, 105-116 (2000).
84. Milligan, E. D. et al. Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J. Neurosci. 23, 1026-1040 (2003).
85. Aumeerally, N., Allen, G. & Sawynok, J. Glutamate-evoked release of adenosine and regulation of peripheral nociception. Neuroscience 127, 1-11 (2004).
86. Raghavendra, V., Tanga, F. & DeLeo, J. A. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J. Pharmacol. Exp. Ther. 306, 624-630 (2003). This paper provides the first evidence that microglia are involved in the initiation, rather than the maintenance, of neuropathic pain.
87. Ledeboer, A. et al. Minocycline attenuates mechanical allodynia and pro-inflammatory cytokine expression in rat models of pain facilitation. Pain 115, 71-83 (2005).
88. Hassel, B., Paulsen, R. E., Johnsen, A. & Fonnum, F. Selective inhibition of glial cell metabolism in vivo by fluorocitrate. Brain Res. 576, 120-124 (1992).
89. Zhang, S. C., Goetz, B. D. & Duncan, I. D. Suppression of activated microglia promotes survival and function of transplanted oligodendroglial progenitors. Glia 41, 191-198 (2003).
90. Tsuda, M. et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424, 778-783 (2003). An important study showing that P2X4 is a key mediator of microglial activation and is involved in neuropathic, but not inflammatory, pain.
91. Guillemin, G. J. & Brew, B. J. Microglia, macrophages perivascular macrophages, and pericytes: a review of function and identification. J. Leukoc. Biol. 75, 388-397 (2004).
92. Colburn, R. W., Rickman, A. J. & DeLeo, J. A. The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp. Neurol. 157, 289-304 (1999),
93. Colburn, R. W. et al. Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat. J. Neuroimmunol. 79, 163-175 (1997).
94. Hashizume, H., DeLeo, J. A., Colburn, R. W. & Weinstein, J. N. Spinal glial activation and cytokine expression after lumbar root injury in the rat. Spine 25 1206-1217 (2000).
95. Winkelstein, B. A. & DeLeo, J. A. Nerve root injury severity differentially modulates spinal glial activation in a rat lumbar radiculopathy model: considerations for persistent pain Brain Res. 956, 294-301 (2002).
96. Raghavendra, V., Tanga, F., Rutkowski, M. D. & DeLeo, J. A. Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines. Pain 104, 655-664 (2003).
97. Tanga, F. Y., Raghavendra, V. & DeLeo, J. A. Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem. Int. 45, 397-407 (2004).
98. Coyle, D. E. Partial peripheral nerve injury leads to activation of astroglia and microglia which parallels the development of allodynic behavior. Glia 23, 75-83 (1998).
99. Zhuang, Z. Y., Gerner, P., Woolf, C. J. & Ji, R. R. ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 114, 149-159 (2005).
100. Le Feuvre, R., Brough, D. & Rothwell, N. Extracellular ATP and P2X7 receptors in neurodegeneration. Eur. J. Pharmacol. 447, 261-269 (2002).
101. Chessell, I. P. et al. Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 114, 386-396 (2005).
102. Klein, M. A. et al. Impaired neuroglial activation in interleukin-6 deficient mice. Glia. 19, 227-233 (1997).
103. Winkelstein, B. A., Rutkowski, M. D., Sweitzer, S. M. Pahl, J. L. & DeLeo, J. A. Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment. J. Comp. Neurol. 439, 127-139 (2001).
104. Tanga, F. Y., Nutile-McMenemy, N. & DeLeo, J. A. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc. Natl Acad. Sci. USA 102, 5856-5861 (2005). Showed, for the first time, the involvement of TLR4 in microglial activation in neuropathic pain models.
105. Kim, S. Y. et al. Activation of p38 MAP kinase in the rat dorsal root ganglia and spinal cord following peripheral inflammation and nerve injury. Neuroreport 13, 2483-2486 (2002).
106. Jin, S. X., Zhuang, Z. Y., Woolf, C. J. & Ji, R. R. 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. 23, 4017-4022 (2003).
107. Tsuda, M., Mizokoshi, A., Shigemoto-Mogami, Y., Koizumi, S. & Inoue, K. Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia 45, 89-95 (2004).
108. Tsuda, M., Inoue, K. & Salter, M. W. Neuropathic pain and spinal microglia: a big problem from molecules in 'small glia. Trends Neurosci. 28, 101-107 (2005). A critical review about the influence of microglia in neuropathic pain.
109. Watkins, L. R. & Maier, S. F. Glia: a novel drug discovery target for clinical pain. Nature Rev. Drug Discov 2, 973-985 (2003).
110. Sung, C. S. et al. Intrathecal interleukin-1β administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord. Brain Res. 1015, 145-153 (2004).
111. Reeve, A. J., Patel, S., Fox, A., Walker, K. & Urban, L. Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. Eur. J. Pain 4, 247-257 (2000).
112. DeLeo, J. A., Colburn, R. W., Nichols, M. & Malhotra, A. Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. J. Interferon Cytokine Res. 16, 695-700 (1996).
113. DeLeo, J. A., Colburn, R. W. & Rickman, A. J. Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy. Brain Res. 759, 50-57 (1997).
114. Holguin, A. et al. HIV-1 gp120 stimulates proinflammatory cytokine-mediated pain facilitation via activation of nitric oxide synthase-I (nNOS). Pain 110, 517-530 (2004).
115. Wu, J., Fang, L., Lin, Q. & Willis, W. D. Nitric oxide synthase in spinal cord central sensitization following intradermal injection of capsaicin. Pain 94, 47-58 (2001).
116. Durrenberger, P. F. et al. Cyclooxygenase-2 (Cox-2) in injured human nerve and a rat model of nerve injury. J. Peripher. Nerv. Syst. 9, 15-25 (2004).
117. Broom, D. C. et al. Cyclooxygenase 2 expression in the spared nerve injury model of neuropathic pain. Neuroscience 124, 891-900 (2004).
118. Schafers, M., Marziniak, M., Sorkin, L. S., Yaksh, T. L. & Sommer, C. Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the rat. Exp. Neurol. 185, 160-168 (2004).
119. Zhu, X. & Eisenach, J. C. Cyclooxygenase-1 in the spinal cord is altered after peripheral nerve injury. Anesthesiology 99, 1175-1179 (2003).
120. Ma, W., Du, W. & Eisenach, J. C. Role for both spinal cord COX-1 and COX-2 in maintenance of mechanical hypersensitivity following peripheral nerve injury. Brain Res. 937, 94-99 (2002).
121. Finnerup, N. B. & Jensen, T. S. Spinal cord injury pain - mechanisms and treatment. Eur. J. Neurol. 11, 73-82 (2004). A good review about spinal cord injury and pain, with a useful section on different underlying mechanisms.
122. Popovich, P. G. Immunological regulation of neuronal degeneration and regeneration in the injured spinal cord. Prog. Brain Res. 128, 43-58 (2000).
123. Watanabe, T. et al. Differential activation of microglia after experimental spinal cord injury. J. Neurotrauma 16, 255-265 (1999).
124. Marchand, F., Grist, J., Bradbury, E. J. & McMahon, S. B. Role of microglia in spinal cord injury pain in rats. Intl Assoc. Study Pain Abstr. 136265 (2005).
125. Gris, D. et al. Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J. Neurosci. 24, 4043-4051 (2004).
126. Oatway, M. A., Chen, Y., Bruce, J. C., Dekaban, G. A. & Weaver, L. C. Anti-CD11d integrin antibody treatment restores normal serotonergic projections to the dorsal, intermediate, and ventral horns of the injured spinal cord. J. Neurosci. 25, 637-647 (2005).
127. Demjen, D. et al. Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury. Nature Med. 10, 389-395 (2004).
128. Pearse, D. D., Pereira, F. C., Stolyarova, A., Barakat, D. J. & Bunge, M. B. Inhibition of tumour necrosis factor-α by antisense targeting produces immunophenotypical and morphological changes in injury-activated microglia and macrophages. Eur. J. Neurosci. 20, 3387-3396 (2004).
129. Perrin, F. E., Lacroix, S., Aviles-Trigueros, M. & David, S. Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and interleukin-1β in Wallerian degeneration. Brain 128, 854-866 (2005).
130. Wang, X. et al. P2X7 receptor inhibition improves recovery after spinal cord injury. Nature Med. 10, 821-827 (2004).
131. Hu, X. et al. Activation of nuclear factor-κB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex. J. Neurochem. 93, 26-37 (2005).
132. L expression after confusion to the rat spinal cord. J. Neurotrauma 18, 1267-1278 (2001).
133. Plunkett, J. A., Yu, C. G., Easton, J. M., Bethea, J. R. & Yezierski, R. P. Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat. Exp. Neurol. 168, 144-154 (2001).
134. Abraham, K. E., McMillen, D. & Brewer K. L. 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 124, 945-952 (2004).
135. Bethea, J. R. et al. Systemically administered interleukin-10 reduces tumor necrosis factor-α production and significantly improves functional recovery following traumatic spinal cord injury in rats. J. Neurotrauma 16, 851-863 (1999).
136. Aicher S. A., Silverman, M. B., Winkler, C. W. & Bebo, B. F. Jr. Hyperalgesia in an animal model of multiple sclerosis. Pain 110, 560-570 (2004).
137. Gilden, D. H. Infectious causes of multiple sclerosis. Lancet Neurol. 4, 195-202 (2005).
138. Vartanian, T. K., Zamvil, S. S., Fox, E. & Sorensen, P. S. Neutralizing antibodies to disease-modifying agents in the treatment of multiple sclerosis. Neurology 63, S42-S49 (2004).
139. Mahad, D. J., Howell, S. J. & Woodroofe, M. N. Expression of chemokines in the CSF and correlation with clinical disease activity in patients with multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 72, 498-502 (2002).
140. Toms, R., Weiner, H. L. & Johnson, D. Identification of IgE-positive cells and mast cells in frozen sections of multiple sclerosis brains. J. Neuroimmunol. 30, 169-177 (1990).
141. Geissmann, F., Jung, S. & Littman, D. R. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71-82 (2003).
142. Panes, J., Perry, M. & Granger, D. N. Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention. Br. J. Phamacol. 126, 537-550 (1999).
143. Murphy, P. M. et al. International Union of Pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol. Rev. 52, 145-176 (2000).
144. Gilroy, D. W., Lawrence, T., Perretti, M. & Rossi, A. G. Inflammatory resolution: new opportunities for drug discovery. Nature Rev. Drug Discov. 3, 401-416 (2004). A review that illustrates the concept of antiinflammation and the endogenous control of the inflammatory response.
145. -/- mouse. FASEB J. 17, 253-255 (2003). This study reports the initial description of the annexin 1 null mouse, and the impact on the host inflammatory response of removing this endogenous inhibitory mediator.
146. Malcangio, M. et al. A novel control mechanism based on GDNF modulation of somatostatin release from sensory neurones. FASEB J. 16, 730-732 (2002).
147. Arita, M. et al. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J. Exp. Med. 201, 713-722 (2005).
148. Ferreira, S. H. et al. Role of lipocortin-1 in the anti-hyperalgesic actions of dexamethasone. Br. J. Pharmacol. 121, 883-888 (1997).
149. Pieretti, S., Di Giannuario, A., De Felice, M., Perretti, M. & Cirino, G. Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides. Pain 109, 52-63 (2004). An important study that describes the effects of annexin 1 bioactive peptidomimetics in models of peripheral inflammatory pain.
150. Melzer, P., Savchenko, V. & McKanna, J. A. Microglia, astrocytes, and macrophages react differentially to central and peripheral lesions in the developing and mature rat whisker-to-barrel pathway: a study using immunohistochemistry for lipocortin1, phosphotyrosine, s100β, and mannose receptors. Exp. Neurol. 168, 63-77 (2001).
151. Le, Y. et al. Amyloid β42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1. J. Neurosci. 21, RC123 (2001). A comprehensive analysis of FPRL1 expression and function on microglia, with strong implications for Alzheimer's disease.
152. Harada, M. et al. N-Formylated humanin activates both formyl peptide receptor-like 1 and 2. Biochem. Biophys. Res. Commun. 324, 255-261 (2004).
153. Minghetti, L. et al. Down-regulation of microglial cyclooxygenase-2 and inducible nitric oxide synthase expression by lipocortin 1. Br. J. Pharmacol. 126, 1307-1314 (1999).