Mechanosensitive ion channels in articular nociceptors drive mechanical allodynia in osteoarthritis

Abstract

These results suggest that MSICs are sensitized during OA and directly contribute to mechanical allodynia. They therefore represent potential therapeutic targets in the treatment of OA pain.

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

“…Activation of nociceptors is central to the experience of pain, and several chronic pain conditions are caused by the sensitization of nociceptors to mechanical stimuli, including osteoarthritis and rheumatoid arthritis pain (He et al, 2017;McQueen et al, 1991;Neogi et al, 2016;Okun et al, 2012;Schaible, 2014). Intervening at the level of primary afferent nociceptors is a promising approach to developing therapeutic treatments.…”

Dynamic regulation of TREK1 gating by Polycystin 2 via a Filamin A-mediated cytoskeletal Mechanism

“…Thus mice lacking the TREK1 channel show a lower threshold to mechanical stimuli 32 . The contribution of these channels is also highlighted during inflammatory pain, in which inflammation causes a decrease in the expression of TREK1 and is associated with reduced thresholds to mechanical stimuli 33 , 34 . Alternatively, the expression level of these potassium-selective MSCs may be unaltered, but their gating by mechanical stimuli can be impaired.…”

Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases

“…We then took advantage of the IL-1R1-restored mouse line (Liu et al, 2015), which exhibits an IL-1R1-knockout phenotype that can be reversed in a cell-specific manner by Cremediated recombination, to investigate whether IL-1R1 + neurons play an important role in the perception of pain after inflammation. For this, we injected nociceptor-specific IL-1R1-restored mice, designated hereafter as Trpv1 Cre ::Il1r1 r/r mice, in the knee with rmIL-1β and monitored the allodynic response using the knee-bend test (Ferreira-Gomes et al, 2008;He et al, 2017). In both WT and Trpv1 Cre ::Il1r1 r/r mice, the injection of IL-1β in the knee capsule produced a transient allodynia during which gentle movements of the knee were associated with nocifensive behaviors.…”

“…The MIA model of OA was induced as previously described (He et al, 2017). Briefly, under isoflurane anesthesia, mice were injected intra-articularly with 5 µl of MIA at a concentration of 50 µg/µl diluted in physiological saline, with the needle passing behind the patellar ligament into the joint space of the left knee.…”