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Spinal gap junctions: potential involvement in pain facilitation.

Leah E Spataro1, Evan M Sloane, Erin D Milligan

  • 1Department of Psychology & The Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado 90309-0345, USA.

The Journal of Pain
|October 27, 2004
PubMed
Summary
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Spinal cord glia contribute to neuropathic pain. Blocking glial gap junctions with carbenoxolone reversed mirror image pain, suggesting gap junction involvement in pain spread and cytokine release.

Area of Science:

  • Neuroscience
  • Pain Research
  • Cellular Biology

Background:

  • Glia play a role in pathological pain.
  • Spinal cord glia have gap junction connections, potentially enabling contralateral pain spread.
  • Neuropathic pain models include sciatic inflammatory neuropathy and chronic constriction injury.

Purpose of the Study:

  • To investigate the role of glial gap junctions in neuropathic pain.
  • To determine if blocking gap junctions can reverse pain symptoms.
  • To explore the mechanisms behind carbenoxolone's effects on pain and cytokines.

Main Methods:

  • Administered intrathecal carbenoxolone, a gap junction decoupler, in rodent models of neuropathic pain.
  • Tested carbenoxolone's effect on mechanical allodynia and thermal hyperalgesia.

Related Experiment Videos

  • Used intrathecal glycyrrhizic acid as a control.
  • Examined carbenoxolone's effects on human immunodeficiency virus type 1 gp120-induced pain and cytokine levels (interleukin-1 and interleukin-6).

    • Main Results:

    • Carbenoxolone reversed mirror image mechanical allodynia in both neuropathic pain models.
    • Carbenoxolone had minimal effect on ipsilateral mechanical allodynia and only briefly attenuated thermal hyperalgesia.
    • Glycyrrhizic acid did not block mechanical allodynia or thermal hyperalgesia, confirming carbenoxolone's effect is due to gap junction decoupling.
    • Carbenoxolone suppressed interleukin-1 and interleukin-6 in response to gp120.

    Conclusions:

    • Gap junctions in the spinal cord are involved in pain facilitation.
    • Blocking gap junctions with carbenoxolone can reverse neuropathic pain, including mirror image pain.
    • Carbenoxolone's pain-blocking effects may involve the suppression of proinflammatory cytokines.
    • Glial gap junction activation may lead to cytokine release by distantly activated glia.