FIG. 1.

Mechanisms that contribute to nociceptive sensitization within the spinal cord. (A) A simplified schematic of key nociceptive pathways. Nociceptive afferents project to the spinal dorsal horn and can engage both a motor response (blue) and ascending fibers that relay pain signals to the brain. Descending pathways (green) regulate nociceptive processing within the dorsal horn. (B) Intense nociceptive input can induce a bilateral overexcitation within the dorsal horn that enhances motor reactivity and pain signals to the brain. (C) Nociceptive input engages glutamatergic neurons within the dorsal horn that can produce a lasting modification in neural excitability through signal pathways analogous to those involved in brain-dependent learning and memory. Akt, protein kinase B; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; BDNF, brain-derived neurotrophic factor; CaMKII, calcium/calmodulin activated protein kinase II; ERK, extracellular signal-regulated kinase; GluR2, glutamate receptor 2; IL-1β, interleukin-1 beta; IP3, inositol 1,4,5-trisphosphate; mGluR, metabotropic glutamate receptor; NMDAR, N-methyl-D-aspartate receptor; PKC, protein kinase C; PLC, phospholipase C; TrkB, tropomyosin receptor kinase B; TNF, tumor necrosis factor; TNFR1, TNF receptor 1.