Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury

Susan M. Carlton, Junhui Du, Huai Yu Tan, Olivera Nesic, Gregory L. Hargett, Anne C. Bopp, Ammar Yamani, Qing Lin, William D. Willis, Claire E. Hulsebosch

    Research output: Contribution to journalArticle

    135 Scopus citations

    Abstract

    Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of above-level CNP. Following a thoracic (T10) contusion, forelimb nociceptors had enhanced spontaneous activity and were sensitized to mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical dorsal horn neurons showed enhanced responses to non-noxious and noxious mechanical stimulation as well as thermal stimulation of receptive fields. Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal damage as a cause for above-level sensitization since few C8 DRG cells expressed AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally, activated microglia and astrocytes were present in thoracic and cervical cord at 35 days post-SCI, indicating a rostral spread of glial activation from the injury site. Based on these data, we conclude that peripheral and central sensitization as well as reactive glia in the uninjured cervical cord contribute to CNP. We hypothesize that reactive glia in the cervical cord release pro-inflammatory substances which drive chronic CNP. Thus a complex cascade of events spanning many cord segments underlies above-level CNP.

    Original languageEnglish (US)
    Pages (from-to)265-276
    Number of pages12
    JournalPain
    Volume147
    Issue number1-3
    DOIs
    StatePublished - Dec 15 2009

    Keywords

    • Astrocyte activation
    • Microglia activation
    • Neuroplasticity
    • Nociception
    • Primary afferents

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Anesthesiology and Pain Medicine

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  • Cite this

    Carlton, S. M., Du, J., Tan, H. Y., Nesic, O., Hargett, G. L., Bopp, A. C., Yamani, A., Lin, Q., Willis, W. D., & Hulsebosch, C. E. (2009). Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury. Pain, 147(1-3), 265-276. https://doi.org/10.1016/j.pain.2009.09.030