Reciprocal Interaction of Pain and Brain: Plasticity-induced Pain, Pain-induced Plasticity, and Therapeutic Targets

Considerable functional and structural alterations, or plasticity, in the central nervous system (CNS) are accompanied by numerous chronic pain syndromes. Sensitization of the peripheral (primary hyperalgesia) or central (secondary hyperalgesia) nervous system as unhelpful neuroplasticity may result in stimulus-induced pain (hyperalgesia and allodynia). Furthermore, nociception induces extensive plasticity in the peripheral and central neural systems in pathological disease states. Diseaseinduced plasticity at both structural and functional levels is evident as alterations in different molecules, synapses, cellular function and network activity. In the present article, we review plasticityinduced pain and pain-induced plasticity. Moreover, we will review the pain matrix. Furthermore, we will focus on recent developments of CNS alterations in long-lasting pain in some clinical entities encountered in rehabilitation. These clinical entities comprise nonspecific low back pain, complex regional pain syndrome, postamputation phantom pain, fibromyalgia, and chronic pain after spinal cord injury. Moreover, we will review the clinical treatment for the inhibition of pathological pain.