ABSTRACT
Protein phosphorylation is a major mechanism for the regulation of N-methyl-D-aspartate receptor (NMDAR) function—one mechanism by which protein kinase C (PKC) regulates the function of NMDARs. PKC also modulates the function of NMDARs by participating in their interactions with postsynaptic density and cytoskeletal proteins. Irrespective of the cause of disinhibition, the unopposed activation of NMDARs is the underlying mechanism. The resulting sensitization of transient receptor potential channel, vanilloid subfamily member 1 (TRPV1) is an important mechanism for heat hyperalgesia and enables the symptoms of chronic pain. Such presynaptic TRPV1 receptors and endogenous capsaicin-like substances found in the paraventricular nucleus (PVN) may indicate a new mechanism in hypothalamic regulation of the autonomic nervous system. The neurons located in the PVN help regulate autonomic function via projections to the brain stem and spinal cord. Agonists of the TRPV1, such as capsaicin, will also induce an analgesic effect after an initial excitatory response.
