Gap junctions, pannexins and pain

Neurosci Lett. 2019 Mar 16;695:46-52. doi: 10.1016/j.neulet.2017.06.035. Epub 2017 Jun 22.


Enhanced expression and function of gap junctions and pannexin (Panx) channels have been associated with both peripheral and central mechanisms of pain sensitization. At the level of the sensory ganglia, evidence includes augmented gap junction and pannexin1 expression in glial cells and neurons in inflammatory and neuropathic pain models and increased synchrony and enhanced cross-excitation among sensory neurons by gap junction-mediated coupling. In spinal cord and in suprapinal areas, evidence is largely limited to increased expression of relevant proteins, although in several rodent pain models, hypersensitivity is reduced by treatment with gap junction/Panx1 channel blocking compounds. Moreover, targeted modulation of Cx43 expression was shown to modulate pain thresholds, albeit in somewhat contradictory ways, and mice lacking Panx1 expression globally or in specific cell types show depressed hyperalgesia. We here review the evidence for involvement of gap junctions and Panx channels in a variety of animal pain studies and then discuss ways in which gap junctions and Panx channels may mediate their action in pain processing. This discussion focusses on spread of signals among satellite glial cells, in particular intercellular Ca2+ waves, which are propagated through both gap junction and Panx1-dependent routes and have been associated with the phenomenon of spreading depression and the malady of migraine headache with aura.

Keywords: Cx43; DRG; GJ: Panx1; Ganglia; Satellite glial cell; Sensory neuron; Spinal cord; TG.

Publication types

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

MeSH terms

  • Animals
  • Connexins / metabolism*
  • Ganglia, Sensory / metabolism
  • Ganglia, Sensory / pathology
  • Gap Junctions / metabolism*
  • Hyperalgesia / metabolism
  • Hyperalgesia / pathology
  • Neuralgia / metabolism
  • Neuralgia / pathology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Pain / metabolism*
  • Pain / pathology
  • Satellite Cells, Perineuronal / metabolism
  • Satellite Cells, Perineuronal / pathology
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / pathology


  • Connexins