Clinical and animal experimental evidences accumulated during the past four decades indicate an evolving change, championed by Patrick D. Wall, from the old concept of a specific pain pathway and hard-wired nervous system to a dynamic concept of plastic neural mechanisms underlying nociceptive processing like other sensory neural functions. These include: (1) the reciprocal sharing and interaction of various somatic sensory modalities between the ascending pathways; (2) the activation of spinal gating mechanisms through a dorsal column brainstem spinal loop; (3) the role of plastic changes in the nervous system in the production and maintenance of chronic pain; (4) the evidence showing that processing of nociception involves the activation of a diffuse network of transmitting fiber tracts and brain centers that are not exclusively devoted to pain; and (5) the consideration of chronic pain, at least in part, as a sign or reflection of a dysfunction in neuroimmune-endocrine regulations.