title: Peripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain.
abstract: Recent evidence implicates an adaptive immune response in the central nervous system (CNS) mechanisms of neuropathic pain. This review identifies how neuropathic pain alters CNS immune privilege to facilitate T cell infiltration. Once in the CNS, T cells may interact with the local antigen presenting cells, microglia, via the major histocompatibility complex and the costimulatory molecules CD40 and B7. In this way, T cells may contribute to the maintenance of neuropathic pain through pro-inflammatory interactions with microglia and by facilitating the activation of astrocytes in the spinal dorsal horn. Based on the evidence presented in this review, we suggest that this bidirectional, pro-inflammatory system of neurons, glia and T cells in neuropathic pain should be renamed the pentapartite synapse, and identifies the latest member as a potential disease-modifying therapeutic target.
authors.affiliation: Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia. peter.grace@adelaide.edu.au
authors.forename: Peter M
authors.initials: PM
authors.lastname: Grace
authors.forename: Paul E
authors.initials: PE
authors.lastname: Rolan
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hutchinson
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology*; D006801:Humans; D009437:Neuralgia / Q000276:immunology*; D009457:Neuroglia / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*