Up-regulation of P2X7 Receptors Contributes to Spinal Microglial Activation and the Development of Pain Induced by BmK-I

Neurosci Bull. 2019 Aug;35(4):624-636. doi: 10.1007/s12264-019-00345-0. Epub 2019 Feb 28.

Abstract

Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I, a Na+ channel activator and a major peptide component of the venom of the scorpion Buthus martensi Karsch (BmK). We found that the expression of P2X7 receptors (P2X7Rs) was up-regulated in the ipsilateral spinal dorsal horn after BmK I injection in rats. P2X7R was selectively localized in microglia but not astrocytes or neurons. Similarly, interleukin 1β (IL-1β) was selectively up-regulated in microglia in the spinal dorsal horn after BmK I injection. Intrathecal injection of P2X7R antagonists largely reduced BmK I-induced spontaneous and evoked pain behaviors, and the up-regulation of P2X7R and IL-1β in the spinal cord. These data suggested that the up-regulation of P2X7Rs mediates microglial activation in the spinal dorsal horn, and therefore contributes to the development of BmK I-induced pain.

Keywords: BmK I; Brilliant Blue G; Interleukin 1β; Microglia; P2X7 receptor; Spinal dorsal horn.

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Interleukin-1beta / metabolism*
  • Male
  • Microglia / metabolism
  • Pain / drug therapy
  • Pain / metabolism*
  • Purinergic P2X Receptor Antagonists / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X7 / metabolism*
  • Scorpion Venoms / pharmacology*
  • Spinal Cord Dorsal Horn / cytology
  • Spinal Cord Dorsal Horn / drug effects
  • Spinal Cord Dorsal Horn / metabolism*

Substances

  • IL1B protein, rat
  • Interleukin-1beta
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Scorpion Venoms
  • makatoxin I