Attempts to clarify the molecular mechanism of anesthesia have not yet been successful. The current controversy is whether the anesthetic action is based on specific or non-specific interaction. From the contradiction in temperature dependence of anesthetic action, we show that anesthetic mechanism cannot be explained by the specific interaction between anesthetic and protein. The leading edge disputes on the anesthetic action will be reviewed.

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The first crystal structure of phosphoenolpyruvate carboxylase (PEPC) has been determined by X-ray diffraction methods at 2.8 Å resolution using Escherichia coli PEPC complexed with L-aspartate, an allosteric inhibitor of all known PEPCs. The four subunits are arranged in a "dimer-of-dimers" form. The location of the catalytic site is suggested to be near the C-terminal side of the β-barrel. The binding site for L-aspartate is located about 20 Å away from the catalytic site and four residues (Lys773, Arg832, Arg587 and Asn881) are involved in effector binding. Considering the catalytically essential Arg587 is in a highly conserved glycine-rich loop, which is characteristic of PEPC, it seems that L-aspartate causes inhibition by removing this glycine-rich loop from the catalytic site.

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The insistent signal of pain is a warning to the body of a threatening event. Painful sensations in the limbs and internal organs signal illness or injury, causing us to rest and thereby give the body's defence system a chance to eliminate the source of harm. On the other hand, prolonged tissue damage or injury often leads to chronic pain states such that noxious stimuli evoke hyperalgesia and innocuous tactile stimuli evoke pain or pain-related behavior (allodynia). The underlying mechanisms for these pathological conditions involve plastic changes in synaptic transmission in the spinal cord.

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