Oxidative Stress in the Amygdala Contributes to Neuropathic Pain

B. Sagalajev, H. Wei, Z. Chen, I. Albayrak, A. Koivisto, A. Pertovaara*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

16 Citations (Scopus)

Abstract

Earlier studies indicate that the central nucleus of the amygdala (CeA) contributes to neuropathic pain. Here we studied whether amygdaloid administration of antioxidants or antagonists of TRPA1 that is among ion channels activated by oxidative stress attenuates nociceptive or affective pain in experimental neuropathy, and whether this effect involves amygdaloid astrocytes or descending serotonergic pathways acting on the spinal 5-HT1A receptor. The experiments were performed in rats with spared nerve injury (SNI). Drugs were administered through a chronic cannula in the CeA or internal capsule (control site), and an intrathecal catheter. Nociception was assessed using monofilaments and affective pain using conditioned place-aversion. Antioxidants or TRPA1 antagonists in the CeA attenuated both nociceptive and affective pain in SNI animals but not in sham controls or in a control injection site. Drugs influencing astroglia (a gap junction decoupler or a D-amino acid oxidase inhibitor) in the CeA had no effect on SNI rats, whereas local anesthesia of the CeA attenuated nociception. Spinally administered 5-HT1A receptor antagonist at a dose that had no effect alone prevented the antinociceptive effect of amygdaloid TRPA1 blockers. The results suggest that injury-induced amygdaloid oxidative stress that drives TRPA1 promotes neuropathic pain behavior. This pronociceptive effect involves suppression of medullospinal serotonergic feedback-inhibition acting on the spinal 5-HT1A receptor. While the CeA is involved in mediating the nerve injury-induced pronociception, it may not be a critical relay for the recruitment of medullospinal feedback-inhibition.

Original languageEnglish
Pages (from-to)92-103
JournalNeuroscience
Volume387
DOIs
Publication statusPublished - 1 Sep 2018
MoE publication typeA1 Journal article-refereed

Keywords

  • Amygdala
  • Antioxidant
  • Descending pain modulation
  • Neuropathic pain
  • Spinal 5-HT receptor
  • Transient receptor potential ankyrin 1

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