Anesthetics Regulation Of Spinal Inhibitory Amino Acid Receptor Mechanisms And Function

General anesthetics, with a diverse range of chemical structures, have been used for more than 150 years in clinical practice, but it is only recently that progress has been made in our understanding of how they exert their effects. It is accepted that general anesthetics primarily exert their anesthetic action via interacting directly with proteins. In the past two decades, at least 30 kinds of ion channels in the membrane of neurons have been observed to be sensitive to general anesthetics at clinical relevant concentrations. However, interlinking the function changes of ion channels and receptors with endpoint behavior effects of general anesthetics is still a great challenge. Barbiturates-induced hyperalgesia, which was first observed by Clutton-Brock more than 40 years ago, has been widely accepted on both clinical and experimental grounds, but its underlying mechanism was little touched until now. Recently, accumulated evidence suggests that the spinal cord, the primary centre for pain signal processing, plays a critical role in at least two anesthetic end-points: analgesia and immobility in response to noxious stimulation. It is reasonable that barbiturates exert their hyperalgesia by acting on spinal cord. On the other hand, it is accepted that GABA_A receptors are deeply involved in modulation of pain. However, the action of another main inhibitory receptor, glycine (Gly) receptor, in regulation of pain is unclear. Not long ago, Ahmadi, Harvey and their colleagues demonstrated that α₃-Gly receptor located on superficial layer of dorsal horn was an essential target for spinal PGE₂-mediated inflammatory pain sensitization, indicating that Gly receptor, at least some subunits, involve in regulating pain and hyperalgesia. Furthermore, Gly receptors are almost neglected during anesthesia period, because they primarily express in the spinal cord and brain stem while the brain was formerly considered the main target for general anesthetics.In the present study, we selected thiopental as a representative drug to investigate the effects of general anesthetics on Gly and GABA_A receptors in spinal dorsal horn neurons in detail using whole cell patch-clamp recording, biochemical technique and behavior test and try to elucidate the possible role of Gly receptors in...