Oxidative stress in the spinal cord is an important contributor in capsaicin-induced mechanical secondary hyperalgesia in mice

Erica S. Schwartz, Inhyung Lee, Kyungsoon Chung, Jin Chung

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, thus suggesting ROS involvement in central sensitization. To investigate ROS involvement in central sensitization, the effects of ROS scavengers and donors on pain behaviors were examined in mice. Capsaicin- induced hyperalgesia was used as a pain model since it has 2 distinctive pain components, primary and secondary hyperalgesia representing peripheral and central sensitization, respectively. Capsaicin (25 μg/5 μl) was injected intradermally into the left hind foot. Foot withdrawal frequencies in response to von Frey filament stimuli were measured and used as an indicator of mechanical hyperalgesia. The production of ROS was examined by using a ROS sensitive dye, MitoSox. Mice developed primary and secondary mechanical hyperalgesia after capsaicin injection. A systemic or intrathecal post-treatment with either phenyl-N-tert-butylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1 oxyl (TEMPOL), ROS scavengers, significantly reduced secondary hyperalgesia, but not primary hyperalgesia, in a dose-dependent manner. Pretreatment with ROS scavengers also significantly reduced the magnitude and duration of capsaicin-induced secondary hyperalgesia. On the other hand, intrathecal injection of tert-butylhydroperoxide (t-BOOH, 5 μl), a ROS donor, produced a transient hyperalgesia in a dose-dependent manner. The number of MitoSox positive dorsal horn neurons was increased significantly after capsaicin treatment. This study suggests that ROS mediates the development and maintenance of capsaicin-induced hyperalgesia in mice, mainly through central sensitization and that the elevation of spinal ROS is most likely due to increased production of mitochondrial superoxides in the dorsal horn neurons.

Original languageEnglish (US)
Pages (from-to)514-524
Number of pages11
JournalPain
Volume138
Issue number3
DOIs
StatePublished - Sep 15 2008

Fingerprint

Capsaicin
Hyperalgesia
Reactive Oxygen Species
Spinal Cord
Oxidative Stress
Central Nervous System Sensitization
Posterior Horn Cells
Pain
Foot
tert-Butylhydroperoxide
Spinal Injections
Superoxides
Coloring Agents
Maintenance

Keywords

  • Central sensitization
  • Free radicals
  • Persistent pain
  • ROS

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

Oxidative stress in the spinal cord is an important contributor in capsaicin-induced mechanical secondary hyperalgesia in mice. / Schwartz, Erica S.; Lee, Inhyung; Chung, Kyungsoon; Chung, Jin.

In: Pain, Vol. 138, No. 3, 15.09.2008, p. 514-524.

Research output: Contribution to journalArticle

Schwartz, Erica S. ; Lee, Inhyung ; Chung, Kyungsoon ; Chung, Jin. / Oxidative stress in the spinal cord is an important contributor in capsaicin-induced mechanical secondary hyperalgesia in mice. In: Pain. 2008 ; Vol. 138, No. 3. pp. 514-524.
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