What can in vivo electrophysiology in animal models tell us about mechanisms of anaesthesia?

The search for the mechanisms of anaesthesia has resulted in an overwhelming multitude of cellular and subcellular sites identi®ed as potential targets of anaesthetic action. Attempts to de®ne a unitary mechanism of action for the diverse types of chemicals with anaesthetic potency have failed, and it is now recognized that agent-speci®c effects on de®ned neuronal sites, including the constituents of synaptic transmission, may underlie their actions. The next step in answering the question `how do anaesthetics cause anaesthesia?' is to associate these cellular mechanisms of actionÐmost of which were described using in vitro experimentsÐwith areas and neuronal networks within the nervous system (`where do anaesthetics cause anaesthesia?') using preparations with fully intact pathways. Combining the knowledge gained from in vitro experiments with clinical experience, animal experiments can be designed to take the questions about anaesthetic actions to the level of the living organism. This approach is important, as it is controversial which of the many effects of anaesthetics demonstrated in vitro are important for producing relevant in vivo effects, such as hypnosis, amnesia, analgesia/antinociception, and the suppression of movement in response to noxious stimulation. 114 The production of unconsciousness (hypnosis) and inhibition of memory formation (amnesia) require effects on cortical function; 120 on the other hand, the suppression of motor and autonomic responses to noxious stimuli and the inhibition of sensory processing may well occur at subcortical sites. Many anaesthetic agents, in clinically used doses, can produce several components of anaesthesia, but they typically show a pro®le of preferred actions. Moreover, neurotransmitter receptors and other putative neuronal targets of anaesthetics (such as voltage-gated or background ion channels) have a distinct distribution and density in the central nervous system (CNS). For example, the GABAA receptors in different regions of the CNS are composed of varying combinations of subunits which differ in their sensitivity to anaesthetics. Therefore, anaesthetics may preferentially affect certain regions of the CNS and may show, for example, a `top-down' or `bottom-up' effectiveness with increasing dose within the hierarchically organized neural systems. This review will focus on in vivo animal studies recording neuronal activity in the peripheral nervous system (PNS) and CNS involved in the different aspects of the anaesthetic state induced by general anaesthetics. We discuss a selection of studies undertaken with this aim, but further data can be hidden especially in electrophysiological investigations on CNS functioning, where the anaesthesia of the experimental animal is a necessary but not central issue. A common end point for studies on anaesthetic mechanisms is the withdrawal response to noxious stimulation, which comprises a motor and a sensory component and some information processing with all three readily assessable in electrophysiological recordings. The suppression of sensory perception is accessible for study in animal models; the site within the ascending sensory pathways and the neuronal networks affected by anaesthetics and their targets among the constituents of synaptic transmission can be explored. As suppression of pain is one of the major goals of anaesthesia and, indeed, most in vivo studies on the mechanisms of anaesthesia address questions about processing of pain and touch, this review will focus on the somatosensory system (see Fig. 1). There are few studies on suppression of hearing, another interesting aspect of anaesthesia in the operating room. Hypnosis and amnesia are British Journal of Anaesthesia 89 (1): 123±42 (2002)