Chronic inflammatory pain and the neurovascular unit: A central role for glia in maintaining BBB integrity?

C. L. Willis, T. P. Davis

Research output: Contribution to journalReview articlepeer-review

52 Scopus citations


Pain is a complex phenomenon involving both a peripheral innate immune response and a CNS response as well as activation of the hypothalamic-pituitary-adrenal axis. The peripheral innate immune response to injury involves the rapid production and local release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and IL-6. Recent studies into the CNS response to peripheral chronic inflammatory pain strongly implicates a role for glia, and local synthesis of proinflammatory cytokines and growth factors. A characteristic feature of CNS inflammation is gliosis, in which inflammatory mediators activate glial cells (e.g. astrocytes and microglia, macrophages and leukocytes) which have been shown to induce and maintain hyperalgesia. In addition, inflammatory pain induces changes in blood-brain barrier (BBB) permeability and alters transport of clinically relevant drugs used to treat pain into the brain. Despite the increasing body of evidence for the involvement of glia in chronic pain and the role of gila in maintaining the BBB, few studies have addressed glial/endothelial interactions and the mechanisms by which glia may regulate the BBB during inflammatory pain. Further studies into the cellular mechanisms of glial/endothelial interactions may identify novel therapeutic targets for reversing chronic inflammatory induced BBB dysfunction and innovate therapies for modulating the severity of chronic inflammatory pain.

Original languageEnglish (US)
Pages (from-to)1625-1643
Number of pages19
JournalCurrent Pharmaceutical Design
Issue number16
StatePublished - Jun 2008

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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