Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury

Supinder S. Bedi, Qing Yang, Robyn J. Crook, Junhui Du, Zizhen Wu, Harvey M. Fishman, Raymond J. Grill, Susan M. Carlton, Edgar T. Walters

    Research output: Contribution to journalArticle

    70 Citations (Scopus)

    Abstract

    Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury3dto8months earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared with untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 months. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C- and Aδ-fibers revealed SCI-induced SA generated in or near the somata of the neurons in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.

    Original languageEnglish (US)
    Pages (from-to)14870-14882
    Number of pages13
    JournalJournal of Neuroscience
    Volume30
    Issue number44
    DOIs
    StatePublished - Nov 3 2010

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    Nociceptors
    Carisoprodol
    Spinal Cord Injuries
    Neurons
    Pain
    Diagnosis-Related Groups
    Myelinated Nerve Fibers
    Capsaicin
    Incidence
    Sensory Receptor Cells
    Lectins
    Neuroglia
    Chronic Pain
    Hypersensitivity
    Thorax
    Hot Temperature
    Inflammation
    Wounds and Injuries
    Research

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury. / Bedi, Supinder S.; Yang, Qing; Crook, Robyn J.; Du, Junhui; Wu, Zizhen; Fishman, Harvey M.; Grill, Raymond J.; Carlton, Susan M.; Walters, Edgar T.

    In: Journal of Neuroscience, Vol. 30, No. 44, 03.11.2010, p. 14870-14882.

    Research output: Contribution to journalArticle

    Bedi, Supinder S. ; Yang, Qing ; Crook, Robyn J. ; Du, Junhui ; Wu, Zizhen ; Fishman, Harvey M. ; Grill, Raymond J. ; Carlton, Susan M. ; Walters, Edgar T. / Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 44. pp. 14870-14882.
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    AU - Yang, Qing

    AU - Crook, Robyn J.

    AU - Du, Junhui

    AU - Wu, Zizhen

    AU - Fishman, Harvey M.

    AU - Grill, Raymond J.

    AU - Carlton, Susan M.

    AU - Walters, Edgar T.

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