Fig. 1

The spinal dorsal horn and S1 neuroplasticity mechanism inducing chronic pain following PNS or CNS injury. A Synaptic modifications in the dorsal horn of the spinal cord result in a balance alteration of excitatory and inhibitory synaptic transmission in lamina I projection neurons to the brain, which account at least partially for pain sensation evoked by non-noxious stimuli. The continuous lines and arrows indicate allodynia-relevant circuits while dotted lines indicate neuronal activity suppression or synaptic loss in the cause of enhanced pathology. Arrowheads indicate the direction of excitatory inputs. PV, parvalbumin-expressing neurons; SOM, somatostatin-expressing neurons; CCK, cholecystokinin-expressing neurons; VGLUT3, vesicular glutamate transporter 3-expressing neurons; PKCγ, protein kinase C gamma-expressing neurons; CR, calretinin-expressing neurons; Gly, glycine-expressing neurons; Netrin-4, netrin-4-expressing neurons; Npy, neuropeptide Y inhibitory interneurons; PN, projection neuron; LTMR, low-threshold mechanoreceptors; V, vertical cells; IIo, outer lamina II, IIi, inner lamina II; IIid, inner lamina II (dorsal); IIiv, inner lamina II (ventral); Aβ, Aβ myelinated fibers; Aδ, Aδ myelinated fibers; C, C fibers. B Axonal sprouting and circuit functional reorganization of S1 involving both intracortical neurons and projection neurons are at least partially responsible for inducing pain by non-noxious stimuli. The continuous lines and arrows indicate allodynia-relevant circuits, and dotted lines indicate suppressed neuronal activity or synaptic losses in the cause of enhanced pathology. Arrowheads indicate the direction of excitatory inputs. White circle (L5a) indicates decreased neuronal hyperactivity after injury. L, layer; Pyr, pyramidal neurons; PV, parvalbumin-expressing neurons; SOM, somatostatin-expressing interneurons; VIP, vasoactive intestinal polypeptide-expressing interneurons; PO, neurons from the thalamic posterior nucleus