Prolonged chemogenetic inhibition of nociceptors in a murine surgical model of osteoarthritis: effects on immune responses in dorsal root ganglia

Abstract

Purpose: Destabilization of the medial meniscus (DMM) in mice leads to progressive joint damage and associated pain-related behaviors, including knee hyperalgesia and mechanical allodynia in the ipsilateral hind paw. After DMM, cellular changes occur in the knee-innervating L4 dorsal root ganglia (DRG) compared to sham and naïve controls, including increased numbers of F4/80+ macrophages. In other chronic pain models, both pro-inflammatory M1 macrophages and CD206-expressing M2 macrophages infiltrate the DRGs and it has been reported that M2 macrophages can produce TGF-β, which can sensitize nociceptive sensory neurons via TGF-β1 receptor (TGFβR1).