In vivo electrophysiological analysis of mechanisms of monoaminergic pain inhibitory systems

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There is abundant evidence that “emergency painless injury” occurs when a severe injury occurs in emergency conditions. This phenomenon is not rare; for example, it is well known that most soldiers who are severely wounded on the battlefield do not report pain.55–57 While they retain other basic senses, such as hearing, smell, and vision, their sense of pain is selectively impaired under emergency conditions. It is safe to assume that this selective impairment of pain sensation is consistent with the protective function of pain by playing a critical role in allowing injured individuals to maintain clear judgment to escape from a dangerous situation. This selective suppression of pain is mediated by the descending pain inhibitory systems, including the serotonergic and noradrenergic systems.55–57 There are many ways to analyze the functions and synaptic transmission of peripheral and central nervous system (CNS) neurons, such as behavioral pharmacology, neurochemistry, neuropharmacology, neurobiology, and neuroimaging.55,56 Electrophysiology may be one of the most important methods for understanding the mechanisms of nociceptive transmissions in the spinal cord. Electrophysiological approaches primarily involve extracellular,23,24,49 intracellular, and patch-clamp recordings (Fig. 1).
These approaches have both advantages and disadvantages. For instance, an extracellular recording can be made from peripheral and central neurons, measuring the change in excitability of a nerve or neuron by the number of action potentials (Fig. 1).22–24 However, it is usually impossible to analyze synaptic responses, with a few exceptions. In contrast, an intracellular recording can analyze changes in excitability or synaptic responses of peripheral and central neurons, but this method is limited to relatively large cells.9,10,36 Patch-clamp recordings can be adapted to in vitro studies12,14,16,26,30,33,35,38,42,43 and in vivo studies of small to large CNS cells.12,14,16,18,20,21,27–29,33,35,39,47,48 With an infrared differential interference contrast (IR-DIC) microscope that enables us to visualize individual neurons, we can easily make recordings from any neurons in voltage-clamp preparations,51 although this method is not applicable for analyzing CNS neurons in vivo. Nevertheless, blind patch-clamp recordings without the IR-DIC microscope system may be a useful way to obtain recordings from neurons located near the surface of the brain in vivo.5
This review provides a brief history of electrophysiological recording methods and describes the physiological mechanisms of descending pain inhibitory systems using data from in vivo patch-clamp recordings18,25,46,50 combined with in vitro slice studies.
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