Up-regulation of P2X7 Receptors Contributes to Spinal Microglial Activation and the Development of Pain Induced by BmK-I
1 Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China
2 Department of Pharmacology and Toxicology and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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
P2X7 receptor; BmK I; Spinal dorsal horn; Interleukin 1β; Microglia Brilliant Blue G