Gap junctions in dorsal root ganglia: possible contribution to visceral pain.
Peripheral injuries can lead to sensitization of neurons in dorsal root ganglia (DRGs), which can contribute to chronic pain. The neurons are sensitized by a combination of physiological and biochemical changes, whose full details are still obscure. Another cellular element in DRGs are satellite glial cells (SGCs), which surround the neurons, but little is known about their role in nociception. We investigated the contribution of SGCs to neuronal sensitization in isolated S1 DRGs from a mouse model of colonic inflammation induced by local application of dinitrosulfonate benzoate (DNBS). Retrograde labeling was used to identify DRG neurons projecting to the colon. Cell-to-cell coupling was determined by intracellular dye injection, and the electrical properties of the neurons were studied with intracellular electrodes. Pain behavior was assessed with von-Frey hairs. The dye injections showed that 10-12 days after DNBS application there was a 6.6-fold increase in gap junction-mediated coupling between SGCs surrounding adjacent neurons, and this occurred preferentially (another 2-fold increase) near neurons that project to the colon. Neuron-neuron coupling incidence increased from 0.7% to 12.1% by colonic inflammation. Inflammation led to an augmented neuronal excitability, and to a reduced pain threshold. Gap junction blockers abolished the inflammation-induced changes in SGCs and neurons, and significantly reversed the pain behavior. We propose that inflammation induces augmented cell coupling in DRGs that contributes to neuronal hyperexcitability, which in turn leads to visceral pain. Gap junction blockers may have potential as analgesic drugs.
Hebrew University-Hadassah Medical School, Mount Scopus, Jerusalem, Israel.
Tian-Ying
TY
Huang
Vitali
V
Belzer
Menachem
M
Hanani
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology / Q000503:physiopathology*; D017629:Gap Junctions / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000187:drug effects; D010146:Pain / Q000473:pathology / Q000503:physiopathology*; D011984:Sensory Receptor Cells / Q000187:drug effects; D016707:Tissue Fixation
C045305:2,4-dinitrofluorobenzene sulfonic acid; D004139:Dinitrofluorobenzene