Hyperexcitable neurons and altered non-neuronal cells in the compressed spinal ganglion.
The cell body or soma in the dosal root ganglion (DRG) is normally excitable and this excitability can increase and persist after an injury of peripheral sensory neurons. In a rat model of radicular pain, an intraforaminal implantation of a rod that chronically compressed the lumbar DRG ("CCD" model) resulted in neuronal somal hyperexcitability and spontaneous activity that was accompanied by hyperalgesia in the ipsilateral hind paw. By the 5th day after onset of CCD, there was a novel upregulation in neuronal expression of the chemokine, monocyte chemoattractant protein-1 (MCP-1 or CCL2) and also its receptor, CCR2. The neurons developed, in response to topically applied MCP-1, an excitatory response that they normally do not have. CCD also activated non-neuronal cells including, for example, the endothelial cells as evidenced by angiogenesis in the form of an increased number of capillaries in the DRG after 7 days. A working hypothesis is that the CCD induced changes in neurons and non-neuronal cells that may act together to promote the survival of the injured tissue. The release of ligands such as CCL2, in addition to possibly activating nociceptive neurons (maintaining the pain), may also act to preserve injured cells in the face of ischemia and hypoxia, for example, by promoting angiogenesis. Thus, somal hyperexcitability, as often said of inflammation, may represent a double edged sword.
LaMotte
Robert H
RH
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510, USA. robert.lamotte@yale.edu
Ma
Chao
C
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000473:pathology*; D006930:Hyperalgesia / Q000473:pathology; D009457:Neuroglia / Q000166:cytology; D009619:Nociceptors / Q000166:cytology*; D010146:Pain / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013117:Spinal Cord Compression / Q000503:physiopathology*; D015854:Up-Regulation
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2