Long-term potentiation (LTP), referring to a lasting increase in efficacy of synaptic transmission, is a common mechanism of
memory storage in central nervous system (CNS). LTP at C-fiber synapses in spinal dorsal horn is considered as a synaptic model of
pathological pain, as the spinal LTP is only induced by noxious electrical and natural stimuli but not by innoxious ones and LTPinducible
stimulation is capable of leading to lasting behavioral signs of pathological pain in human and in animals. The molecular
mechanisms of spinal LTP at C-fiber synapses are similar to hippocampal LTP in following aspects. Induction of LTP depends on postsynaptic
Ca2+ rise resulting from opening of N-methyl-D-aspartate channels (NMDA) and voltage-gated calcium channels (VGCCs), and
Ca2+ release from intracellular store; Early-phase LTP (<3h) needs activation of intracellular protein kinase A (PKA), protein kinase C
(PKC), calcium/calmodulin-dependent protein kinase II (CaMKII), phospholipase C (PLC) and release of nitric oxide (NO); Late-phase
LTP (>3h) is dependent on de novo protein synthesis; Activation of either dopamine D1 receptors or PKA, and extrogenous brain-derived
neurotrophic factor (BDNF) or ATP directly induces late-phase LTP. Therefore, the drugs targeting at the above molecules may impair
memory function of hippocampus. The striking difference between hippocampal LTP and spinal LTP at C-fiber synapses is that activation
of glial cells and the over–expression of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin–
beta (IL-1β), inhibit LTP in hippocampus, but promote LTP in spinal dorsal horn. The drugs targeting at the neuroinflammatory process
may not only attenuate pathological pain but also improve memory in hippocampus.
Keywords: Long-term potentiation, C-fiber, spinal dorsal horn, pathological pain, hippocampus, proinflammatory cytokine.
Rights & PermissionsPrintExport