The imbalance in the central and peripheral mechanisms of pain includes the direct activation or the increment in the sensitivity of the nociceptors to different stimuli, such as joint inflammation, through the elevation of pro-inflammatory cytokines released by immune cells in the synovium, including TNF-α, IL-1β, IL-6, and IL-17, which directly alter the responses of nociceptive neurons [43]. The gene discussed is TNF; the disease is Arthritis.