Senolytics Reduce Pain But Not Cartilage Damage in Osteoarthritis in Mice

In this interesting paper, researchers investigate the mechanisms by which senolytics can reduce pain in osteoarthritis, while not affecting cartilage degeneration. This outcome appears to involve changes in sensitivity-related signaling that affects the behavior of the peripheral nervous system in and around the damaged areas of the joint. Cartilage is one of the least regenerative tissues in the body. The effective treatment of cartilage damage, it seems, will need more than merely removing the causes of damage to date, but also regenerative therapies to repair the existing damage. Both clinical and preclinical research suggest that osteoarthritis (OA)-related pain is induced by increased nociceptive input from the joint through alterations in pain signaling pathways in the central and peripheral nervous system. For example, activation of nociceptive neurons in the dorsal root ganglion (DRG) through nerve growth factor (NGF) to activate nociceptive neurons by binding tropomyosin receptor kinase A (TrkA), chemokine (C-C motif) ligand 2 (CCL2), tumor necrosis factor (TNF), and Netrin-1 correlates with OA-related pain. Moreover, these axon guidance proteins induce nociceptive neuron projection locally in multiple joint tissues, including synovium and subchondral bone, leading to an exaggerated pain response. Currently, it is unknown whether senolytic drugs affect the degree of innervation of sensory nerve fibers in the synovium and subchondral bone and if there...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs