Skin Incision Induces Expression of Axonal Regeneration-Related Genes in Adult Rat Spinal Sensory Neurons

  • Caitlin E. Hill
    University of Miami, The Miami Project to Cure Paralysis, Miami, Florida
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  • Benjamin J. Harrison
    University of Louisville, Department of Anatomical Sciences and Neurobiology, Louisville, Kentucky

    Kentucky Spinal Cord Injury Research Center, University of Louisville, Department of Neurological Surgery, Louisville, Kentucky
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  • Kris K. Rau
    University of Louisville, Department of Anatomical Sciences and Neurobiology, Louisville, Kentucky

    Kentucky Spinal Cord Injury Research Center, University of Louisville, Department of Neurological Surgery, Louisville, Kentucky
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  • M. Tyler Hougland
    University of Louisville, Department of Anatomical Sciences and Neurobiology, Louisville, Kentucky

    Kentucky Spinal Cord Injury Research Center, University of Louisville, Department of Neurological Surgery, Louisville, Kentucky
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  • Mary Bartlett Bunge
    University of Miami, The Miami Project to Cure Paralysis, Miami, Florida
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  • Lorne M. Mendell
    SUNY Stony Brook, Department of Neurobiology and Behavior, Stony Brook, New York
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  • Jeffrey C. Petruska
    Address reprint requests to Jeffrey C. Petruska, University of Louisville, Dept. of Anatomical Sciences and Neurobiology, 500 S. Preston Street, Louisville, KY 40202.
    University of Louisville, Department of Anatomical Sciences and Neurobiology, Louisville, Kentucky

    Kentucky Spinal Cord Injury Research Center, University of Louisville, Department of Neurological Surgery, Louisville, Kentucky
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      Skin incision and nerve injury both induce painful conditions. Incisional and postsurgical pain is believed to arise primarily from inflammation of tissue and the subsequent sensitization of peripheral and central neurons. The role of axonal regeneration-related processes in development of pain has only been considered when there has been injury to the peripheral nerve itself, even though tissue damage likely induces injury of resident axons. We sought to determine if skin incision would affect expression of regeneration-related genes such as activating transcription factor 3 (ATF3) in dorsal root ganglion (DRG) neurons. ATF3 is absent from DRG neurons of the normal adult rodent, but is induced by injury of peripheral nerves and modulates the regenerative capacity of axons. Image analysis of immunolabeled DRG sections revealed that skin incision led to an increase in the number of DRG neurons expressing ATF3. RT-PCR indicated that other regeneration-associated genes (galanin, GAP-43, Gadd45a) were also increased, further suggesting an injury-like response in DRG neurons. Our finding that injury of skin can induce expression of neuronal injury/regeneration-associated genes may impact how clinical postsurgical pain is investigated and treated.


      Tissue injury, even without direct nerve injury, may induce a state of enhanced growth capacity in sensory neurons. Axonal regeneration-associated processes should be considered alongside nerve signal conduction and inflammatory/sensitization processes as possible mechanisms contributing to pain, particularly the transition from acute to chronic pain.

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