Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model

Osteoarthritis (OA) is the most prevalent joint disease associated with chronic pain. OApain is often accompanied by mood disorders. We addressed the role of the Prokineticin (PK) systemin pain and mood alterations in a mice OA model induced with monosodium iodoacetate (MIA). Theeffect of a PK antagonist (PC1) was compared to that of diclofenac. C57BL/6J male mice injected withMIA in the knee joint were characterized by allodynia, motor deficits, and fatigue. Twenty-eight daysafter MIA, in the knee joint, we measured high mRNA of PK2 and its receptor PKR1, pro-inflammatorycytokines, and MMP13. At the same time, in the sciatic nerve and spinal cord, we found increasedlevels of PK2, PKR1, IL-1β, and IL-6. These changes were in the presence of high GFAP and CD11bmRNA in the sciatic nerve and GFAP in the spinal cord. OA mice were also characterized byanxiety, depression, and neuroinflammation in the prefrontal cortex and hippocampus. In bothstations, we found increased pro-inflammatory cytokines. In addition, PK upregulation and reactiveastrogliosis in the hippocampus and microglia reactivity in the prefrontal cortex were detected. PC1reduced joint inflammation and neuroinflammation in PNS and CNS and counteracted OA pain andemotional disturbances.