Immune and inflammatory mechanisms in neuropathic pain

Brain Res Rev. 2006 Aug;51(2):240-64. doi: 10.1016/j.brainresrev.2005.11.004. Epub 2006 Jan 4.


Tissue damage, inflammation or injury of the nervous system may result in chronic neuropathic pain characterised by increased sensitivity to painful stimuli (hyperalgesia), the perception of innocuous stimuli as painful (allodynia) and spontaneous pain. Neuropathic pain has been described in about 1% of the US population, is often severely debilitating and largely resistant to treatment. Animal models of peripheral neuropathic pain are now available in which the mechanisms underlying hyperalgesia and allodynia due to nerve injury or nerve inflammation can be analysed. Recently, it has become clear that inflammatory and immune mechanisms both in the periphery and the central nervous system play an important role in neuropathic pain. Infiltration of inflammatory cells, as well as activation of resident immune cells in response to nervous system damage, leads to subsequent production and secretion of various inflammatory mediators. These mediators promote neuroimmune activation and can sensitise primary afferent neurones and contribute to pain hypersensitivity. Inflammatory cells such as mast cells, neutrophils, macrophages and T lymphocytes have all been implicated, as have immune-like glial cells such as microglia and astrocytes. In addition, the immune response plays an important role in demyelinating neuropathies such as multiple sclerosis (MS), in which pain is a common symptom, and an animal model of MS-related pain has recently been demonstrated. Here, we will briefly review some of the milestones in research that have led to an increased awareness of the contribution of immune and inflammatory systems to neuropathic pain and then review in more detail the role of immune cells and inflammatory mediators.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System / immunology
  • Central Nervous System / physiopathology
  • Chemotaxis, Leukocyte / immunology
  • Humans
  • Inflammation / immunology*
  • Inflammation / physiopathology*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / physiopathology
  • Neuralgia / immunology*
  • Neuralgia / physiopathology*
  • Neuroglia / immunology
  • Neuroglia / metabolism
  • Peripheral Nerves / immunology
  • Peripheral Nerves / physiopathology
  • Peripheral Nervous System Diseases / immunology*
  • Peripheral Nervous System Diseases / physiopathology*


  • Inflammation Mediators