Pain regulation by non-neuronal cells and inflammation

Science. 2016 Nov 4;354(6312):572-577. doi: 10.1126/science.aaf8924.


Acute pain is protective and a cardinal feature of inflammation. Chronic pain after arthritis, nerve injury, cancer, and chemotherapy is associated with chronic neuroinflammation, a local inflammation in the peripheral or central nervous system. Accumulating evidence suggests that non-neuronal cells such as immune cells, glial cells, keratinocytes, cancer cells, and stem cells play active roles in the pathogenesis and resolution of pain. We review how non-neuronal cells interact with nociceptive neurons by secreting neuroactive signaling molecules that modulate pain. Recent studies also suggest that bacterial infections regulate pain through direct actions on sensory neurons, and specific receptors are present in nociceptors to detect danger signals from infections. We also discuss new therapeutic strategies to control neuroinflammation for the prevention and treatment of chronic pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacterial Infections / immunology
  • Bacterial Infections / physiopathology
  • Chronic Pain / drug therapy
  • Chronic Pain / etiology
  • Chronic Pain / physiopathology*
  • Ganglia, Spinal / physiopathology
  • Humans
  • Keratinocytes / physiology
  • Macrophages / physiology
  • Mice
  • Monocytes / physiology
  • Neoplasms / physiopathology
  • Neuritis / complications
  • Neuritis / drug therapy
  • Neuritis / physiopathology*
  • Neuroglia / physiology
  • Nociceptors / immunology
  • Nociceptors / physiology*
  • Pain / physiopathology*
  • Rats
  • Spinal Cord / physiopathology
  • T-Lymphocytes / physiology
  • Toll-Like Receptors / physiology


  • Toll-Like Receptors