Peripheral neurosteroids enhance P2X receptor-induced mechanical allodynia via a sigma-receptor-mediated mechanism

Soon Gu Kwon, Seo Yeon Yoon, Dae Hyun Roh, Sheu Ran Choi, Hoon Seong Choi, Ji Young Moon, Suk Yun Kang, Alvin J. Beitz, Jang Hern Lee

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The role of peripheral neurosteroids and their related mechanisms on nociception have not been thoroughly investigated. Based on emerging evidence in the literature indicating that neurosteroids and their main target receptors, i.e., sigma-1, GABAA and NMDA, affect P2X-induced changes in neuronal activity, this study was designed to investigate the effect of peripherally injected dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulfate (PREGS) on P2X receptor-mediated mechanical allodynia in rats. Intraplantar injection of either neurosteroids alone did not produced any detectable changes in paw withdrawal frequency to the innocuous mechanical stimulation in naïve rats. However, When DHEAS or PREGS were co-injected with a sub-effective dose of αβmeATP, mechanical allodynia was developed and this was dose dependently blocked by pre-injection of the P2X antagonist, TNP-ATP. These results demonstrates that DHEAS and PREGS potentiate the activity of P2X receptors which results in the enhancement of αβmeATP-induced mechanical allodynia. In order to investigate the potential role of peripheral sigma-1, GABAA and NMDA receptors in this facilitatory action, we pretreated animals with BD-1047 (sigma-antagonist), muscimol (GABAA agonist) or MK-801 (NMDA antagonist) prior to DHEAS or PREGS + αβmeATP injection. Only BD-1047 effectively prevented the facilitatory effects induced by neurosteroids on αβmeATP-induced mechanical allodynia. Collectively, we have shown that peripheral neurosteroids potentiate P2X-induced mechanical allodynia and that this action is mediated by sigma-1, but not by GABAA nor NMDA, receptors.

Original languageEnglish (US)
Pages (from-to)227-232
Number of pages6
JournalBrain Research Bulletin
Volume121
DOIs
StatePublished - Mar 1 2016

Keywords

  • Dehydroepiandrosterone sulphate
  • Mechanical allodynia
  • Neurosteroid
  • P2X
  • Pregnenolone sulfate
  • Sigma-receptor

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