Chemogenetic Inhibition of Pain Neurons in a Mouse Model of Osteoarthritis.

ABSTRACT:

Objective

To determine the ability of drugs that activate inhibitory G protein-coupled receptors (GPCRs) expressed in peripheral voltage-gated sodium channel 1.8 (Na_V 1.8)-positive sensory neurons to control osteoarthritis (OA)-associated pain.

Methods

We used designer receptors exclusively activated by a designer drug (DREADD) technology, which employs engineered GPCRs to activate or inhibit neurons upon binding the synthetic ligand clozapine N-oxide (CNO). Na_V 1.8-Pdi C57BL/6 mice were generated to express the inhibitory DREADD receptor Pdi in Na_V 1.8-expressing sensory neurons. Destabilization of the medial meniscus (DMM) surgery was performed in 10-week-old male mice. Four, 8, 12, or 16 weeks after surgery, knee hyperalgesia or hind paw m

SUBMITTER: Miller RE 

PROVIDER: S-EPMC5501168 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature