Early blockade of injured primary sensory afferents reduces glial cell activation in two rat neuropathic pain models.
Satellite glial cells in the dorsal root ganglion (DRG), like the better-studied glia cells in the spinal cord, react to peripheral nerve injury or inflammation by activation, proliferation, and release of messengers that contribute importantly to pathological pain. It is not known how information about nerve injury or peripheral inflammation is conveyed to the satellite glial cells. Abnormal spontaneous activity of sensory neurons, observed in the very early phase of many pain models, is one plausible mechanism by which injured sensory neurons could activate neighboring satellite glial cells. We tested effects of locally inhibiting sensory neuron activity with sodium channel blockers on satellite glial cell activation in a rat spinal nerve ligation (SNL) model. SNL caused extensive satellite glial cell activation (as defined by glial fibrillary acidic protein [GFAP] immunoreactivity) which peaked on day 1 and was still observed on day 10. Perfusion of the axotomized DRG with the Na channel blocker tetrodotoxin (TTX) significantly reduced this activation at all time points. Similar findings were made with a more distal injury (spared nerve injury model), using a different sodium channel blocker (bupivacaine depot) at the injury site. Local DRG perfusion with TTX also reduced levels of nerve growth factor (NGF) in the SNL model on day 3 (when activated glia are an important source of NGF), without affecting the initial drop of NGF on day 1 (which has been attributed to loss of transport from target tissues). Local perfusion in the SNL model also significantly reduced microglia activation (OX-42 immunoreactivity) on day 3 and astrocyte activation (GFAP immunoreactivity) on day 10 in the corresponding dorsal spinal cord. The results indicate that early spontaneous activity in injured sensory neurons may play important roles in glia activation and pathological pain.
Xie
W
W
Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0531, USA.
Strong
J A
JA
Zhang
J-M
JM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002045:Bupivacaine / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008026:Ligation; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027161:Satellite Cells, Perineuronal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D015415:Biomarkers; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; C509295:ITGAM protein, human; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D020932:Nerve Growth Factor; D002045:Bupivacaine