Spinal excitatory mechanisms of pathological pain

An important property of the nociceptive system is its plasticity, ie, the ability to change in an experience-dependent manner, which is implicated in the transition from acute pain to chronic pathological pain. Disease-induced plasticity can occur at both structural and functional levels and manifests as changes in individual molecules, synapses, cellular function, and network activity. In this short review, the author discusses how synaptic plasticity may mediate pathophysiological alterations linked to chronic pain by virtue of shifting the balance between excitation and inhibition, with a particular emphasis on the spinal dorsal horn. In particular, mechanisms of spinal synaptic potentiation and how these are manifest as nociceptive hypersensitivity represent an avenue with recent advances. Structural remodeling and reorganization represent another exciting area of advance in our understanding of pain. Here, new insights into maladaptive structural plasticity of spinal synapses and molecular determinants thereof will be discussed. Finally, the role of synapse-to-nucleus communication in mediating long-term changes in nociceptive sensitivity is discussed from the view point of pain chronicity.