Glia: novel counter-regulators of opioid analgesia

Trends Neurosci. 2005 Dec;28(12):661-9. doi: 10.1016/j.tins.2005.10.001. Epub 2005 Oct 24.


Development of analgesic tolerance and withdrawal-induced pain enhancement present serious difficulties for the use of opioids for pain control. Although neuronal mechanisms to account for these phenomena have been sought for many decades, their bases remain unresolved. Within the past four years, a novel non-neuronal candidate has been uncovered that opposes acute opioid analgesia and contributes to development of opioid tolerance and tolerance-associated pain enhancement. This novel candidate is spinal cord glia. Glia are important contributors to the creation of enhanced pain states via the release of neuroexcitatory substances. New data suggest that glia also release neuroexcitatory substances in response to morphine, thereby opposing its effects. Controlling glial activation could therefore increase the clinical utility of analgesic drugs.

Publication types

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

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Drug Tolerance
  • Humans
  • Neuroglia / drug effects
  • Neuroglia / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Nociceptors / drug effects
  • Nociceptors / metabolism
  • Pain / metabolism*
  • Pain / prevention & control*
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism*


  • Analgesics, Opioid
  • Neurotransmitter Agents