Nerve compression activates selective nociceptive pathways and upregulates peripheral sodium channel expression in Schwann cells.
Chronic nerve compression (CNC) injuries, such as carpal tunnel syndrome, are common musculoskeletal conditions that affect patients with debilitating loss of sensory function and pain. Although early detection and treatment are important, our understanding of pain-related molecular mechanisms remains largely unclear. Here we investigate these mechanisms using an animal model for CNC injury. To confirm that CNC injury induces pain, we assessed expression of c-fos, a gene that is rapidly expressed in spinal sensory afferents in response to painful peripheral stimuli, and TNF-alpha and IL-6, two proinflammatory cytokines that are crucial to development of inflammatory-mediated pain. Results show c-fos upregulation 1-2 weeks postinjury in the absence of TNF-alpha or IL-6 expression, indicating increased neural sensitivity without an inflammatory response. This is consistent with previous studies that showed no morphologic evidence of inflammation in the CNC model. Surprisingly, we also found de novo expression of Na(V)1.8, a sodium channel linked to the development of neuropathic pain, in endoneurial Schwann cells following injury. Until now, Na(V)1.8 expression was thought to be restricted to sensory neurons. CNC injury appears to be a unique model of noninflammatory neuropathic pain. Further investigation of the underlying molecular basis could yield promising targets for early diagnosis and treatment.
Frieboes
Laura Rummler
LR
Department of Biomedical Engineering, University of California Irvine, 2226 Gillespie Neuroscience Research Facility, Irvine, California 92697, USA.
Palispis
Winnie Anne
WA
Gupta
Ranjan
R
D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009408:Nerve Compression Syndromes / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D010146:Pain / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism*; D015222:Sodium Channels / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015854:Up-Regulation
D051100:Glial Cell Line-Derived Neurotrophic Factor; D015850:Interleukin-6; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C568319:Scn10a protein, rat; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha