Synonyms
Spinal Cord Astrocyte; Microglia Activation
Definition
Cord glial activation refers to the activation of dorsal spinal cord microglia and astrocytes, which induces exaggerated pain via the release of substances that excite nocisponsive neurons (reviewed in Watkins et al. 2001). Activation is evidenced by upregulation of immunohistochemically-detectable cell-type specific activation markers, and increased release of neuroactive glial products including proinflammatory cytokines, excitatory amino acids (EAA), nitric oxide (NO), adenosine triphosphate (ATP), and prostaglandins. These released substances then act on neurons, thereby amplifying the pain response. Some evidence points to the activation of microglia leading to the activation of astrocytes (Raghavendra et al. 2003).
Characteristics
Glia are non-neuronal cells traditionally thought of as “supportive cells” for neurons(Araque et al. 1999). Many of their functions involve the release of growth factors, protecting neurons...
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Araque A, Parpura V, Sanzgiri RP, Haydon PG (1999) Tripartite Synapses: Glia, The Unacknowledged Partner. Trends in Neurosci 22:208–215
Beaujouan JC, DaguetdeMontety MC, Torrens Y, Saffroy M, Dietl M, Glowinski J (1990) Marked Regional Heterogeneity of 125I-Bolton Hunter Substance P Binding and Substance P-Induced Activation of Phospholipase C in Astrocyte Cultures from the Embryonic or Newborn Rat. J Neurochem 54:669–675
Chang RC, Chen W, Hudson P, Wilson B, Han DS, Hong JS (2001) Neurons Reduce Glial Responses to Lipopolysaccharide (LPS) and Prevent Injury of Microglial Cells from Over-Activation by LPS. J Neurochem 76:1042–1049
Chapman GA, Moores K, Harrison D, Campbell CA, Steward BR, Strijbos PJLM (2000) Fractalkine Cleavage from Neuronal Membranes Represents an Acute Event in the Inflammatory Response to Excitotoxic Brain Damage. Journal of Neuroscience 20: RC87 pp 81–85
Coggeshall RE, Lekan HA, White FA, Woolf CJ (2001) A-Fiber Sensory Input Induces Neuronal Cell Death in the Dorsal Horn of the Adult Rat Spinal Cord. J Comp Neurol 435:276–282
DeLeo JA, Colburn RW (1999) Proinflammatory Cytokines and Glial Cells: Their Role in Neuropathic Pain. In: Watkins L (ed) Cytokines and Pain. Birkhauser, Basel, pp 159–182
Garrison CJ, Dougherty PM, Carlton SM (1994) GFAP Expression in Lumbar Spinal Cord of Naive and Neuropathic Rats Treated with MK-801. Exp Neurol 129:237–243
Garrison CJ, Dougherty PM, Kajander KC, Carlton SM (1991) Staining of Glial Fibrillary Acidic Protein (GFAP) in Lumbar Spinal Cord Increases Following a Sciatic Nerve Constriction Injury. Brain Res 565:1–7
Hassel B, Paulsen RE, Johnson A, & Fonnum F (1992) Selective Inhibition of Glial Cell Metabolism by Fluorocitrate. Brain Res 249:120–124
Meller ST, Dykstra C, Grzybycki D, Murphy S, Gebhart GF (1994) The Possible Role of Glia in Nociceptive Processing and Hyperalgesia in the Spinal Cord of the Rat. Neuropharmacology 33:1471–1478
Milligan ED, Mehmert KK, Hinde JL, Harvey LO, Martin D, Tracey KJ, Maier SF, Watkins LR (2000) 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
Moore KA, Kohno T, Karchewski LA, Scholz J, Baba H, Woolf CJ (2002) Partial Peripheral Nerve Injury Promotes a Selective Loss of GABAergic Inhibition in the Superficial Dorsal Horn of the Spinal Cord. J Neurosci 22:6724–6731
Neumann H (2001) Control of Glial Immune Function by Neurons. Glia 36:191-199
Ochalski PA, Frankenstein UN, Hertzberg EL, Nagy JI (1997) Connexin-43 in Rat Spinal Cord: Localization in Astrocytes and Identification of Heterotypic Astro-Oligodendrocytic Gap Junctions. Neuroscience 76:931–945
Paulsen RE, Contestabile A, Villani L, Fonnum F (1987) An In Vivo Model for Studying Function of Brain Tissue Temporarily Devoid of Glial Cell Metabolism: The Use of Fluorocitrate. J Neurochem 48:1377–1385
Raghavendra V, Tanga F, DeLeo JA (2003) Inhibition of Microglial Activation Attenuates the Development but not Existing Hypersensitivity in a Rat Model of Neuropathy. J Pharmacol Exp Ther 306:624–630
Spataro LE, Sloane E, Milligan ED, Maier SF, Wieseler-Frank J, Schoeniger D, Jekrich BM, Barrientos RM, Watkins LR (2004) Spinal gap junctions: potential involvement in pain facilitation. J Pain 5:392–405
Sugimoto T, Bennett GJ, Kajander KC (1990) Transsynaptic Degeneration in the Superficial Dorsal Horn after Sciatic Nerve Injury: Effects of a Chronic Constriction Injury, Transection, and Strychnine. Pain 42:205–213
Watkins LR, Maier SF (2003) Glia: A Novel Drug Discovery Target for Clinical Pain. Nature Reviews Drug Discovery 2:973–985
Watkins LR, Milligan ED, Maier SF (2001) Glial Activation: A Driving Force for Pathological Pain. Trends Neurosci 24:450–455
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Wieseler-Frank, J., Milligan, E., Maier, S., Watkins, L. (2007). Cord Glial Activation. In: Schmidt, R., Willis, W. (eds) Encyclopedia of Pain. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-29805-2_879
Download citation
DOI: https://doi.org/10.1007/978-3-540-29805-2_879
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-43957-8
Online ISBN: 978-3-540-29805-2
eBook Packages: MedicineReference Module Medicine