Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release

June Guillet, Kwan Yeop Lee, Hee Young Kim, Jigong Wang, Hee Kee Kim, Kyungsoon Chung, Jin Chung

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Although both a loss of spinal inhibitory neurotransmission and the involvement of oxidative stress have been regarded as important mechanisms in the pathogenesis of pain, the relationship between these 2 mechanisms has not been studied. To determine whether reactive oxygen species (ROS) involvement in pain mechanisms is related to the diminished inhibitory transmission in the substantia gelatinosa (SG) of the spinal dorsal horn, behavioral studies and whole-cell recordings were performed in FVB/NJ mice. Neuropathic pain was induced by a tight ligation of the L5 spinal nerve (SNL). Pain behaviors in the affected foot were assessed by behavioral testing for mechanical hyperalgesia. Pain behaviors developed by 3 days and lasted more than 8 weeks. Both systemic and intrathecal administration of an ROS scavenger, phenyl-N-tert-butylnitrone (PBN), temporarily reversed mechanical hyperalgesia up to 2 hours, 1 week after SNL. In nonligated mice, an intrathecal injection of an ROS donor, tert-butyl hydroperoxide (t-BOOH), dose-dependently induced mechanical hyperalgesia for 1.5 hours. In whole-cell voltage clamp recordings of SG neurons, perfusion with t-BOOH significantly decreased the frequency of mIPSCs, and this effect was reversed by PBN. Furthermore, t-BOOH decreased the frequency of GABAA receptor-mediated mIPSCs without altering their amplitudes but did not affect glycine receptor-mediated mIPSCs. In SNL mice, mIPSC frequency in SG neurons was significantly reduced as compared with that of normal mice, which was restored by PBN. The antihyperalgesic effect of PBN on mechanical hyperalgesia was attenuated by intrathecal bicuculline, a GABAA receptor blocker. Our results indicate that the increased ROS in spinal cord may induce pain by reducing GABA inhibitory influence on SG neurons that are involved in pain transmission. An increase in ROS in spinal cord may induce pain by reducing GABA inhibitory influence on substantia gelatinosa neurons that are involved in pain transmission.

Original languageEnglish (US)
Pages (from-to)844-852
Number of pages9
JournalPain
Volume152
Issue number4
DOIs
StatePublished - Apr 2011

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Neuralgia
Substantia Gelatinosa
gamma-Aminobutyric Acid
Reactive Oxygen Species
Pain
Hyperalgesia
Spinal Nerves
Neurons
GABA-A Receptors
Spinal Cord
Glycine Receptors
tert-Butylhydroperoxide
Spinal Injections
Bicuculline
Patch-Clamp Techniques
Synaptic Transmission
Ligation
Foot
Oxidative Stress
Perfusion

Keywords

  • Free radicals
  • GABA dysfunction
  • Inhibitory transmission
  • Persistent pain
  • Spinal cord

ASJC Scopus subject areas

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

Cite this

Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release. / Guillet, June; Lee, Kwan Yeop; Kim, Hee Young; Wang, Jigong; Kim, Hee Kee; Chung, Kyungsoon; Chung, Jin.

In: Pain, Vol. 152, No. 4, 04.2011, p. 844-852.

Research output: Contribution to journalArticle

Guillet, June ; Lee, Kwan Yeop ; Kim, Hee Young ; Wang, Jigong ; Kim, Hee Kee ; Chung, Kyungsoon ; Chung, Jin. / Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release. In: Pain. 2011 ; Vol. 152, No. 4. pp. 844-852.
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