Pathological pain and the neuroimmune interface

Nat Rev Immunol. 2014 Apr;14(4):217-31. doi: 10.1038/nri3621. Epub 2014 Feb 28.


Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms. Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells. In this Review, we discuss the current understanding of the contribution of central immune mechanisms to pathological pain, and how the heterogeneous immune functions of different cells in the CNS could be harnessed to develop new therapeutics for pain control. Given the prevalence of chronic pain and the incomplete efficacy of current drugs--which focus on suppressing aberrant neuronal activity--new strategies to manipulate neuroimmune pain transmission hold considerable promise.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Central Nervous System / immunology
  • Central Nervous System / pathology
  • Central Nervous System / physiopathology
  • Chemokines / immunology
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Models, Biological
  • Neuroimmunomodulation / immunology*
  • Neuroimmunomodulation / physiology*
  • Pain / immunology*
  • Pain / pathology
  • Pain / physiopathology*
  • Pain Management
  • Signal Transduction
  • Toll-Like Receptors / immunology


  • Chemokines
  • Toll-Like Receptors