NROE may cause sustained arousal and thereby negative health consequences, thru for example sensitization [ 45, 46].
Thus, combination therapy with other drugs will be required, for example, for sensitization of apoptotic pathways or suppression of potentially protumoral TRAIL effects, to achieve major and lasting tumor remissions.
A very recent example of sensitization was shown by Winssinger and co-workers, where a thioxanthenone sensitizer is bound to a nucleic acid sequence, which is able to promote the photolysis only when hybridized with a NPPOC-containing sequence with the matching complementary bases.
For example, glutamate produces central sensitization of trigeminal as well as spinal cord dorsal horn neurons [56, 57].
For example, HDAC1 in the sensitization of multidrug-resistant neuroblastoma cell lines to cytotoxic agents, HDAC2 in repressing miR-183-mediated tumor suppression and HDAC3 in negatively regulating tumor suppressor GRHL1.
Sensitization is an example of malfunctioning of the nociceptive pathway in either the peripheral or central nervous system.
For example, the injection of capsaicin produces both peripheral sensitization of C- and A δ-nociceptors and central sensitization of dorsal horn neurons [ 48].
Chemokines can contribute directly to hyperalgesia through G-protein coupled sensitization of ligand gated channels, for example, TRPV1, heterologous desensitization of opioid receptors and sensitization of sensory neurones [ 72, 73].
Schmidt et al. demonstrated a high morphological plasticity of the noradrenergic innervation of the pPVN during sensitization of the HPA axis for example after stress or single administration of IL-1β or amphetamines.
Depending on the mediator, the sensitization of nociceptors can be induced within minutes (for example, by phosphorylation of ion channels in the membrane) or hours [ 23, 26, 27].
