Neurophysiology and Sensitization Mechanisms of Joint Pain

Joint pain is a common clinical problem with diverse causes, including degenerative changes associated with aging and overuse, trauma, metabolic disorders such as gout, and inflammatory diseases such as rheumatoid arthritis.Joints are innervated by Aβ fibers supplying periarticular structures and by nociceptive Aδ and C fibers forming free nerve endings, which play a central role in pain signaling.Under inflammatory conditions, chemical mediators directly excite joint nociceptors and enhance mechanical sensitivity through second messenger systems, leading to peripheral sensitization and recruitment of silent nociceptors.Sustained sensitization is mediated by nerve growth factor and pro-inflammatory cytokines and is associated with alterations in ion channel function.Concomitantly, spinal sensitization develops, characterized by neuronal hyperexcitability and receptive field expansion, which contributes to primary and secondary hyperalgesia and widespread pain.At the supraspinal level, activation of the pain matrix and thalamo-cortical plasticity underlie the sensory, cognitive, and affective dimensions of joint pain.This review integrates current knowledge of joint nociceptive mechanisms across peripheral, spinal, and supraspinal levels in joint disease.(