ABSTRACT
Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of other clinical conditions, including neuropathic pain, spasticity-related pain, and nociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.
ABSTRACT
The synovial membrane undergoes a variety of structural changes throughout the pathogenesis of osteoarthritis (OA), including the development of fibrosis. Fibroblast-like synoviocytes (FLS) are a heterogenous cell population of the synovium that are suggested to drive the fibrotic response, but the exact mechanisms associated with their activation in OA remain unclear. Once activated, FLS are suggested to acquire a myofibroblast-like phenotype that drives fibrogenesis through excessive extracellular matrix (ECM) component deposition and an enhanced contractile function. In this review, we define FLS in the synovium, discuss how select extracellular or endogenous factors potentially induce their activation in OA, and describe how the activity of myofibroblast-like cells affects the structure of the synovial membrane.
