title: Spinal glia and chronic pain.
abstract: Therapeutic management of chronic pain has not been widely successful owing to a lack of understanding of factors that initiate and maintain the chronic pain condition. Efforts to delineate the mechanisms underlying pain long have focused on neuronal elements of pain pathways, and both opiate- and non-opiate-based therapeutics are thought largely to target neurons. Abnormal neuronal activity at the level of spinal cord "pain centers" in the dorsal horn leads to hypersensitivity or a hyperalgesic response subsequent to the initial painful stimulus. Only recently has the experimental literature implicated nonneuronal elements in pain because of the realization that glial-derived signaling molecules can contribute to and modulate pain signaling in the spinal cord. Most notably, glial proinflammatory mediators within the dorsal horn of the spinal cord appear to contribute to self-perpetuating pain. Chronic pain is modeled experimentally through a variety of manipulations of sensory nerves including cutting, crushing, resection, and ligation. The cellular and molecular responses in the spinal cord due to these manipulations often reveal activation of 2 types of glia: microglia and astrocytes. The activation states of both microglia and astrocytes are complex and may be driven by underlying chronic neuropathology and/or a chronically "primed" condition that accounts for their contribution to chronic pain. Recent evidence even suggests that opioid tolerance and withdrawal hyperalgesia may be initiated and maintained via actions of microglia and astroglia. Together, these recent findings suggest that glia will serve as novel therapeutic targets for the treatment of chronic pain. To fully exploit glia as novel therapeutic targets will require a greater understanding of glial biology, as well as the identification of agents able to control the glial reactions involved in chronic pain, without interfering with beneficial glial functions.
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. jdo5@cdc.gov
authors.forename: James P
authors.initials: JP
authors.lastname: O'Callaghan
authors.forename: Diane B
authors.initials: DB
authors.lastname: Miller
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000209:etiology*; D013116:Spinal Cord / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid