Glial activation and pathological pain.
Pain is a sensation we have all experienced. For most of us, the pain has been temporary. However, for patients with pathological pain, the pain experience is unending, with little hope for therapeutic relief. Pathological pain is characterized by an amplified response to normally innocuous stimuli, and an amplified response to acute pain. Pathological pain has long been described as the result of dysfunctional neuronal activity. While neuronal functioning is indeed altered, there is significant evidence showing that exaggerated pain is regulated by the activation of astrocytes and microglia. In exaggerated pain, astrocytes, and microglia are activated by neuronal signals including substance P, glutamate, and fractalkine. Activation of glia by these substances leads to the release of mediators that then act on other glia and neurons. These include a family of proteins called "proinflammatory cytokines" released from microglia and astrocytes. These cytokines have been shown to be critical mediators of exaggerated pain. Some patients with pathological pain also report "extra-territorial" and/or "mirror" image pain. That is, exaggerated pain is experienced not only in the area of trauma. In extra-territorial pain, pain is also perceived as arising from neighboring healthy tissues outside of the site of trauma. In the rare cases of mirror-image pain, such pain is perceived as arising from the healthy, corresponding body part on the opposite side of the body. New data suggest that activation of astrocyte communication via gap junctions may mediate such spread of pain. While traditional therapies for pathological pain have focused on neuronal targets, the following review describes glia as newly recognized mediators of exaggerated pain, and as new therapeutic targets. Moreover, the glial-neuronal interactions discussed here are likely not exclusive to pain, but rather are likely to play significant roles in other behavioral phenomena.
Wieseler-Frank
Julie
J
Department of Psychology, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO 80309-0345, USA. frankjw@psych.colorado.edu
Maier
Steven F
SF
Watkins
Linda R
LR
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D006801:Humans; D009457:Neuroglia / Q000473:pathology / Q000502:physiology*; D010146:Pain / Q000473:pathology*