DREADDed microglia in pain: Implications for spinal inflammatory signaling in male rats.

DREADDed microglia in pain: Implications for spinal inflammatory signaling in male rats.
Exp Neurol. 2018 Mar 09;:
Authors: Grace PM, Wang X, Strand KA, Baratta MV, Zhang Y, Galer EL, Yin H, Maier SF, Watkins LR
Abstract
The absence of selective pharmacological tools is a major barrier to the in vivo study of microglia. To address this issue, we developed a Gq- and Gi-coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) to enable selective stimulation or inhibition of microglia, respectively. DREADDs under a CD68 (microglia/macrophage) promoter were intrathecally transfected via an AAV9 vector. Naïve male rats intrathecally transfected with Gq (stimulatory) DREADDs exhibited significant allodynia following intrathecal administration of the DREADD-selective ligand clozapine-N-oxide (CNO), which was abolished by intrathecal interleukin-1 receptor antagonist. Chronic constriction injury-induced allodynia was attenuated by intrathecal CNO in male rats intrathecally transfected with Gi (inhibitory) DREADDs. To explore mechanisms, BV2 cells were stably transfected with Gq or Gi DREADDs in vitro. CNO treatment induced pro-inflammatory mediator production per se from cells expressing Gq-DREADDs, and inhibited lipopolysaccharide- and CCL2-induced inflammatory signaling from cells expressing Gi-DREADDs. These studies are the first to manipulate microglia function using DREADDs, which allow the role of glia in pain to be...

Source: Experimental Neurology - March 9, 2018 Category: Neurology Authors: Grace PM, Wang X, Strand KA, Baratta MV, Zhang Y, Galer EL, Yin H, Maier SF, Watkins LR Tags: Exp Neurol Source Type: research