TRPV1 channels make major contributions to behavioral hypersensitivity and spontaneous activity in nociceptors after spinal cord injury

Zizhen Wu, Qing Yang, Robyn J. Crook, Roger G. O'Neil, Edgar T. Walters

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Chronic neuropathic pain is often a severe and inadequately treated consequence of spinal cord injury (SCI). Recent findings suggest that SCI pain is promoted by spontaneous activity (SA) generated chronically in cell bodies of primary nociceptors in dorsal root ganglia (DRG). Many nociceptors express transient receptor potential V1 (TRPV1) channels, and in a preceding study most dissociated DRG neurons exhibiting SA were excited by the TRPV1 activator, capsaicin. The present study investigated roles of TRPV1 channels in behavioral hypersensitivity and nociceptor SA after SCI. Contusive SCI at thoracic segment T10 increased expression of TRPV1 protein in lumbar DRG 1 month after injury and enhanced capsaicin-evoked ion currents and Ca2+ responses in dissociated small DRG neurons. A major role for TRPV1 channels in pain-related behavior was indicated by the ability of a specific TRPV1 antagonist, AMG9810, to reverse SCI-induced hypersensitivity of hind limb withdrawal responses to mechanical and thermal stimuli at a dose that did not block detection of noxious heat. Similar reversal of behavioral hypersensitivity was induced by intrathecal oligodeoxynucleotides antisense to TRPV1, which knocked down TRPV1 protein and reduced capsaicin-evoked currents. TRPV1 knockdown also decreased the incidence of SA in dissociated nociceptors after SCI. Prolonged application of very low concentrations of capsaicin produced nondesensitizing firing similar to SA, and this effect was enhanced by prior SCI. These results show that TRPV1 makes important contributions to pain-related hypersensitivity long after SCI, and suggest a role for TRPV1-dependent enhancement of nociceptor SA that offers a promising target for treating chronic pain after SCI.

Original languageEnglish (US)
Pages (from-to)2130-2141
Number of pages12
JournalPain
Volume154
Issue number10
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Transient Receptor Potential Channels
Nociceptors
Vasopressin Receptors
Spinal Cord Injuries
Hypersensitivity
Capsaicin
Spinal Ganglia
Pain
Chronic Pain
Hot Temperature
Neurons
Aptitude
Oligodeoxyribonucleotides
Neuralgia
Proteins
Thorax
Extremities
Ions

Keywords

  • Allodynia Capsaicin Dorsal root ganglion Hyperalgesia Pain Spinal contusion

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

TRPV1 channels make major contributions to behavioral hypersensitivity and spontaneous activity in nociceptors after spinal cord injury. / Wu, Zizhen; Yang, Qing; Crook, Robyn J.; O'Neil, Roger G.; Walters, Edgar T.

In: Pain, Vol. 154, No. 10, 2013, p. 2130-2141.

Research output: Contribution to journalArticle

Wu, Zizhen ; Yang, Qing ; Crook, Robyn J. ; O'Neil, Roger G. ; Walters, Edgar T. / TRPV1 channels make major contributions to behavioral hypersensitivity and spontaneous activity in nociceptors after spinal cord injury. In: Pain. 2013 ; Vol. 154, No. 10. pp. 2130-2141.
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