Peripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain

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.