Anesthesia and Pain Signal transmission and Control Mechanisms of Ion transporters

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Although the action of ion-transporters is vital in living cell and organisms, there have been only few studies in which roles of ion-transporters have been investigated on the aspect of anesthesia and pain transmission. Since we have examined how local anesthetics could affect Na^+-K^+ATPase (Na pump) activity using in vivo experiments of rats. We found that since their inhibitors administered into spinal subarachinoid caused significant antinociceptive action, Na^+-K^+ATPase (Na pump) and Na^+-H^+ exchanger would have significant role in local anesthetic action at the spinal cord level, but not with Na^+-K^+-2CL cotranspoter. Oubabain and amiloride seem not to affect signaling molecules such as mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinases (ERKs), PKC, and PLC. Local anesthetic tetracaine induces apoptosis of PC12 cells via phosphorylation of MAPK family. ERK activation protects cells from death, but JNK plays the opposite role. Toxic Ca^<2+> influx caused by tetracaine seems to be responsible for apoptotic cell death, but blocking of Na^+ channels and L-type Ca^<2+> channels is unlikely involved in such tetracaine's action on signaling molecules for apoptosis. Using neuronal acitivity of rat's dorsal root ganglion we also found that NMDA receptor antagonists such as ketamine and ifenprodil, as well as Class 1c antiarrhythmics such as flecainide and pilsicainide could also affect TTX resistant Na+ channel activity. Using cardiac myocytes, intravenous anesthetics, midazolam suppresses thrombin-induced heat shock protein 27 phosphorylation through inhibition of p38 mitogen-activated protein kinaseOur studies indicate that local anesthetics as well as intravenous anesthetics used clinically could affect ion channel and ion-transporters via modulation of intracellular signaling molecules. The results suggested that such action would seem to play some roles in anesthetic action and pain transmission.