The DOI matches its Crossref record; 279 of the 279 references it cites were found in a registry or an index.
Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States
Abstract
Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibility that the reason for this failure lies in the fact that such drugs were designed to target neurons rather than immune or glial cells. It describes how immune cells are a natural and inextricable part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the etiology and symptomatology of diverse pathological pain states in both humans and laboratory animals. Of the variety of substances released by activated immune and glial cells, proinflammatory cytokines (tumor necrosis factor, interleukin-1, interleukin-6) appear to be of special importance in the creation of peripheral nerve and neuronal hyperexcitability. Although this review focuses on immune modulation of pain, the implications are pervasive. Indeed, all nerves and neurons regardless of modality or function are likely affected by immune and glial activation in the ways described for pain.
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Items 201–279 of 279
Intraneural activated T cells cause focal breakdown of the blood-nerve barrier
Spies, J. M., Westland, K. W., Bonner, J. G., & Pollard, J. D. (1995) · Brain · doi:10.1093/brain/118.4.857 · Cited by 77
Miyamoto, H., Saura, R., Harada, T., Doita, M., & Mizuno, K. (2000) · PubMed · Cited by 75
Leukemia Inhibitory Factor: Part of a Large Ingathering Family
Taupin, J., Pitard, V., Déchanet‐Merville, J., Miossec, V., Gualde, N., & Moreau, J. (1998) · International Reviews of Immunology · doi:10.3109/08830189809043003 · Cited by 75
Ogun-Muyiwa, P., Helliwell, R. J. A., McIntyre, P., & Winter, J. (1999) · Neuroreport · doi:10.1097/00001756-199907130-00021 · Cited by 75
Bonetti, B., Invernizzi, F., Rizzuto, N., Bonazzi, M. L., Zanusso, G., Chinaglia, G., & Monaco, S. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(96)00191-9 · Cited by 73
The Role of Cytokines in Schwann Cell Damage, Protection, and Repair
Lisak, R. P., Skundric, D. S., Bealmear, B., & Ragheb, S. (1997) · The Journal of Infectious Diseases · doi:10.1086/513788 · Cited by 73
Evidence for Immune System Involvement in Reflex Sympathetic Dystrophy
CALDER, J. S., Holten, I. W. R., & McALLISTER, R. M. R. (1998) · Journal of Hand Surgery (European Volume) · doi:10.1016/s0266-7681(98)80162-9 · Cited by 72
Hyperalgesia from subcutaneous cytokines
Poole, S., Cunha, F. Q., & Ferreira, S. H. (1999) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8749-6_4 · Cited by 71
Wallerian degeneration and hyperalgesia after peripheral nerve injury are glutathione-dependent
Wagner, R., Heckman, H. M., & Myers, R. R. (1998) · Pain · doi:10.1016/s0304-3959(98)00091-8 · Cited by 69
Reactive oxygen species mediate A??(25-35)-induced activation of BV-2 microglia
Kang, J., Park, E. J., Jou, I., Kim, J., & Joe, E.-H. (2001) · Neuroreport · doi:10.1097/00001756-200105250-00030 · Cited by 68
Induction of nociceptive responses by intrathecal injection of interleukin-1 in mice
Tadano, T., Namioka, M., Nakagawasai, O., Tan–No, K., Matsushima, K., Endo, Y., & Kisara, K. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00244-1 · Cited by 67
Shubayev, V. I., & Myers, R. R. (2002) · Journal of the Peripheral Nervous System · doi:10.1046/j.1529-8027.2002.02003.x · Cited by 66
Bathon, J. M., Manning, D. C., GOLDMAN, D. W., Towns, M. C., & Proud, D. (1992) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)11244-5 · Cited by 66
Xiao, W.-H., Yu, A. L.-T., & Sorkin, L. S. (1997) · Pain · doi:10.1016/s0304-3959(96)03280-0 · Cited by 64
Reflex sympathetic dystrophy: facts and hypotheses
Kurvers, H. (1998) · Vascular Medicine · doi:10.1177/1358836x9800300305 · Cited by 64
Potentiation of Neutrophil Function by Recombinant DNA-Produced Interleukin 1a
Ozaki, Y., Ohashi, T., & Kume, S. (1987) · Journal of Leukocyte Biology · doi:10.1002/jlb.42.6.621 · Cited by 63
Shimaoka, S., Tsuboi, R., Jindo, T., Imai, R., Takamori, K., Rubin, J. S., & Ogawa, H. (1995) · Journal of Cellular Physiology · doi:10.1002/jcp.1041650214 · Cited by 62
Tumour necrosis factor-alpha and other cytokines in Guillain-Barre syndrome.
Exley, A., Smith, N., & Winer, J. B. (1994) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.57.9.1118 · Cited by 62
Ruocco, I., Cuello, A. C., & Ribeiro‐da‐Silva, A. (2000) · The Journal of Comparative Neurology · Cited by 61
Guillain‐Barré Syndrome: Multifactorial Mechanisms versus Defined Subgroups
van der Meché, F. G. A., Visser, L. H., Jacobs, B. C., Endtz, H. P., Meulstee, J., & van Doorn, P. A. (1997) · The Journal of Infectious Diseases · doi:10.1086/513779 · Cited by 58
Kurvers, H. A. J. M., Daemen, M. A. R. C., Slaaf, D. W., Stassen, F. R. M., van den Wildenberg, F. A. J. M., Kitslaar, P. J. E. H. M., & Mey, J. G. R. D. (1998) · PubMed · Cited by 57
Olsson, Y., Kristensson, K., & KLATZO, I. (1971) · Springer eBooks · doi:10.1007/978-3-642-47449-1_8 · Cited by 56
Wilkinson, M. F., Earle, M. L., Tricole, C. R., & Barnes, S. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.7.8635696 · Cited by 56
The diagnostic value of sural nerve T cells in chronic inflammatory demyelinating polyneuropathy
Bosboom, W. M., van den Berg, L. H., de Boer, L., Son, M. J. V., Veldman, H., Franssen, H., Logtenberg, T., & Wokke, J. H. J. (1999) · Neurology · doi:10.1212/wnl.53.4.837 · Cited by 55
Clatworthy, A. L., Castro, G. A., Budelmann, B., & Walters, E. T. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-05-03263.1994 · Cited by 54
Romero, F. J., Monsalve, E., Hermenegildo, C., Puertas, F. J., Higueras, V., Nies, E., Segura‐Aguilar, J., & Rom�, J. (1991) · Neurochemical Research · doi:10.1007/bf00965704 · Cited by 54
The Role of Endoneurial Fibroblasts in Myelin Degradation
Schubert, T. B., & Friede, R. L. (1981) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198103000-00006 · Cited by 53
Human Skin Mast Cells Produce TNF-α by Substance P
Okayama, Y., Ono, Y., Nakazawa, T., et al. (1998) · International Archives of Allergy and Immunology · doi:10.1159/000053571 · Cited by 53
Sawant‐Mane, S., Clark, M. B., & Koski, C. L. (1991) · Annals of Neurology · doi:10.1002/ana.410290410 · Cited by 53
Sharief, M. K., Ingram, D. A., & Swash, M. (1997) · Annals of Neurology · doi:10.1002/ana.410420112 · Cited by 50
Role of the Blood-Nerve Barrier in Experimental Nerve Edema
Mizisin, A. P., KALICHMAN, M. W., Myers, R. R., & Powell, H. C. (1990) · Toxicologic Pathology · doi:10.1177/019262339001800123 · Cited by 49
Slart, R. H. J. A., Yu, A. L.-T., Yaksh, L. T., & Sorkin, S. (1997) · Pain · doi:10.1016/s0304-3959(96)03247-2 · Cited by 48
Thompson, S., & Majithia, A. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.809bv.x · Cited by 47
Kawakami, M., Matsumoto, T., Kuribayashi, K., & Tamaki, T. (1999) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100170620 · Cited by 47
Intracerebroventricular Injection of Tumor Necrosis Factor-αInduces Thermal Hyperalgesia in Rats
Oka, T., Wakugawa, Y., Hosoi, M., Oka, K., & Hori, T. (1996) · NeuroImmunoModulation · doi:10.1159/000097238 · Cited by 46
Murwani, R., Hodgkinson, S. J., & Armati, P. J. (1996) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(96)00131-2 · Cited by 46
Bosboom, W. M. J., van den Berg, L. H., Mollee, I., et al. (2001) · Neurology · doi:10.1212/wnl.56.1.74 · Cited by 46
Thompson, S., Priestley, J. V., & Southall, A. (1998) · Neuroscience · doi:10.1016/s0306-4522(97)00553-8 · Cited by 45
Non-neural-specific T lymphocytes can orchestrate inflammatory peripheral neuropathy
Harvey, G. K., Gold, R., Hartung, H., & Toyka, K. V. (1995) · Brain · doi:10.1093/brain/118.5.1263 · Cited by 45
Structure/function relationships of Fcγ receptors in phagocytosis
Indik, Z. K., Park, J.-G., HUNTER, S. E., & Schreiber, A. D. (1995) · Seminars in Immunology · doi:10.1016/1044-5323(95)90007-1 · Cited by 43
A Neuroimmune Interaction in Painful Peripheral Neuropathy
Bennett, G. J. (2000) · Clinical Journal of Pain · doi:10.1097/00002508-200009001-00005 · Cited by 43
Leem, J., & Bove, G. M. (2002) · Journal of Pain · doi:10.1054/jpai.2002.27138 · Cited by 40
Humoral Mechanisms in Immune Neuropathies
Koski, C. L. (1992) · Neurologic Clinics · doi:10.1016/s0733-8619(18)30201-9 · Cited by 40
Kawakami, M., Tamaki, T., Hayashi, N., Hashizume, H., Matsumoto, T., Minamide, A., & Kihira, T. (2000) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100180214 · Cited by 39
Sawada, M., Hara, N., & Maéno, T. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90458-l · Cited by 38
Isolation and characterization of the third component of rat complement.
Daha, M. R., Stuffers-Heiman, M., Kijlstra, A., & van Es, L. A. (1979) · PubMed · Cited by 37
Irnich, D., Tracey, D. J., Polten, J., Burgstahler, R., & Grafe, P. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00556-5 · Cited by 36
Sz�cs, A., Stefano, G. B., Hughes, T. K., & S.-R�zsa, K. (1992) · Cellular and Molecular Neurobiology · doi:10.1007/bf00711543 · Cited by 36
Noack, H., Possel, H., Rethfeldt, C., Keilhoff, G., & Wolf, G. L. (1999) · Glia · doi:10.1002/(sici)1098-1136(199910)28:1<13::aid-glia2>3.0.co;2-l · Cited by 36
Antioxidants in peripheral nerve
Romero, F. J. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)02183-3 · Cited by 35
Effect of rhTNF-α injection into rat sciatic nerve
Uncini, A., Muzio, A. D., Guglielmo, G., Angelis, M. V. D., Luca, G. D., Lugaresi, A., & Gambi, D. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00229-x · Cited by 34
Eckert, A., von Banchet, G. S., Sopper, S., & Petersen, M. (1999) · Pain · doi:10.1016/s0304-3959(99)00152-9 · Cited by 34
Hyperalgesia due to nerve injury—role of peroxynitrite
Liu, T., Knight, K. R., & Tracey, D. J. (2000) · Neuroscience · doi:10.1016/s0306-4522(99)00566-7 · Cited by 34
van der Laan, L., Kapitein, P. J. C., Verhofstad, A. A. J., Hendriks, T., & Goris, R. J. A. (1998) · PubMed · Cited by 30
Pathology of inflammatory demyelinating neuropathies.
Prineas, J. W. (1994) · PubMed · Cited by 29
Immune-mediated alterations in nociceptive sensory function in Aplysia californica
Clatworthy, A. L., & Grose, E. (1999) · Journal of Experimental Biology · doi:10.1242/jeb.202.5.623 · Cited by 29
Neurotrophin-like immunoreactivity in the human trigeminal ganglion
Quartu, M., Geic, M., & Fiacco, M. D. (1997) · Neuroreport · doi:10.1097/00001756-199711100-00038 · Cited by 27
The membrane attack complex of complement mediates peripheral nervous system demyelination in vitro
Br�ck, W., Br�ck, Y., Diederich, U., & Piddlesden, S. J. (1995) · Acta Neuropathologica · doi:10.1007/bf00318572 · Cited by 26
Neurogenic Modifications Induced by Substance P in an Organ Culture of Human Skin
Branchet, M., Boisnic, S., Charpentier, Y. L., Nonotte, I., Montastier, C., & Breton, L. (1999) · Skin Pharmacology and Physiology · doi:10.1159/000066245 · Cited by 26
Liu, H. M., Lei, H., & Kao, K. (1995) · Experimental Neurology · doi:10.1016/0014-4886(95)90055-1 · Cited by 26
van der Goot, F. G., Pugin, J., Hribar, M., Fransen, L., Dunant, Y., BAETSELIER, P. D., Bloc, A., & Lucas, R. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01294-6 · Cited by 25
Daemen, M. J. A. P., Kurvers, H. A. J. M., Bullens, P. H. J., et al. (1998) · PubMed · Cited by 23
Roles of thromboxane A2 and leukotriene B4 in radicular pain induced by herniated nucleus pulposus
Kawakami, M., Matsumoto, T., & Tamaki, T. (2001) · Journal of Orthopaedic Research® · doi:10.1016/s0736-0266(00)90032-9 · Cited by 22
Oka, N., Akiguchi, I., Kawasaki, T., Ohnishi, K., & Kimura, J. (1994) · Annals of Neurology · doi:10.1002/ana.410350518 · Cited by 22
Protein kinase A-dependent IL-6 production induced by calcitonin in human glioblastoma A172 cells
Kiriyama, Y., Murayama, T., Tokumitsu, Y., & Nomura, Y. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00044-1 · Cited by 21
Cell death in vasculitic neuropathy
Heuß, D. F., Probst‐Cousin, S., Kayser, C., & Neund�rfer, B. (2000) · Muscle & Nerve · doi:10.1002/1097-4598(200007)23:7<999::aid-mus1>3.0.co;2-i · Cited by 21
Suzuki, Y., Tanihara, M., Ichikawa, Y., Osanai, A., Nakagawa, M., Ide, M., & Mizushima, Y. (1995) · Annals of the Rheumatic Diseases · doi:10.1136/ard.54.6.484 · Cited by 21
Patrizio, M., Colucci, M., & Levi, G. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0740400.x · Cited by 19
Trojano, M., Avolio, C., Ruggieri, M., et al. (1998) · Multiple Sclerosis Journal · doi:10.1177/135245859800400110 · Cited by 19
Kavelaars, A., van Steenwijk, T. D. J.-D. V., Kuis, W., & Heijnen, C. J. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09608.x · Cited by 18
Effect of interleukin 1 beta on transducing mechanisms in 235-1 clonal pituitary cells
Schettini, G., Florio, T., Meucci, O., Scala, G., Landolfi, E., & GRIMALDI, M. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81252-x · Cited by 17
SHIMADA, K., Koh, C. S., & Yanagisawa, N. (1993) · PubMed · Cited by 16
Continuous infusion of acidified saline around the rat sciatic nerve produces thermal hyperalgesia
Maves, T. J., Gebhart, G. F., & Meller, S. T. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11722-9 · Cited by 15
Effect of interleukin 1 beta on transducing mechanisms in 235-1 clonal pituitary cells
Schettini, G., Meucci, O., Florio, T., Scala, G., Landolfi, E., & GRIMALDI, M. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81253-1 · Cited by 14
Papir-Kricheli, D., & Devor, M. G. (1988) · Somatosensory & Motor Research · doi:10.3109/08990228809144641 · Cited by 14
Gap junctional communication between the satellite cells of rat dorsal root ganglia.
Sakuma, E., Wang, H. J., Asai, Y., Tamaki, D., Amano, K., Mabuchi, Y., Herbert, D. C., & Soji, T. (2001) · PubMed · Cited by 13
Receptors for immunoglobulin G demonstrated on human peripheral nerve fibres by electron microscopy
Vederler, C. A., & Fitzpatrick-Kløve, L. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90449-j · Cited by 12
Preclinical analysis of radiolabeled anti-GD2 immunoglobulin G
Vriesendorp, F. J., Quadri, S. M. S., Flynn, R. E., Malone, M. R., Cromeens, D. M., Stephens, L. C., & Vriesendorp, H. M. (1997) · Cancer · Cited by 10
Wiethölter, H., Krüger, J., Melville, C., & Cornelius, C.-P. (1993) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(93)90156-s · Cited by 9
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Latremoliere, A., & Woolf, C. J. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2009.06.012 · Cited by 3,913
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728
Ramesh, G., MacLean, A. G., & Philipp, M. T. (2013) · Mediators of Inflammation · doi:10.1155/2013/480739 · Cited by 639
Raghavendra, V., Tanga, F. Y., & DeLeo, J. A. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300315 · Cited by 263
Hughes, S., Jaremka, L. M., Alfano, C. M., Glaser, R., Povoski, S. P., Lipari, A. M., Agnese, D. M., Farrar, W. B., Yee, L. D., Carson, W. E., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.12.016 · Cited by 213
Metadata
- Authors
- Watkins, L. R., & Maier, S. F.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2002-01-10
- Volume
- 82
- Issue
- 4
- Pages
- 981-1011
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2160779124
- Cited by
- 733
- References
- 279
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
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