Peculiarities of Ion Channels and Modulation of Their Functions in Neurons Belonging to the Nociceptive System

Abstract

This review deals with the questions related to the composition of ion channels in the membranes of neurons belonging to the nociceptive system; special attention is focused on channels belonging to the TRP family. The factors (in particular, genetically determined) influencing the activity of these channels are discussed. The roles of certain enzymes (protein kinases, phospholipases, etc.) in modulation of the functioning of channel structures typical of nociceptive neurons are reviewed. The roles of calcium transmembrane currents and the state of cellular calcium-controlling compartments in transmission of nociceptive signals are also discussed. Special attention is paid to long-lasting modulatory changes in the activity of different ion channels responsible for the development of stable shifts of sensitive abilities of the nociceptive system (hyperalgesia, hypoalgesia, and allodynia) typical of certain neurological disorders.From a general biological aspect, processes responsible for reception of pain influences and central processing of the corresponding information are the most important components of functioning of the sensory systems in vertebrates (including humans) and some other animal groups. Pain perception allows the organism to avoid the action of stimuli dangerous for normal vital functions and to keep the organism's integrity. Dysfunctions of the nociceptive system can result in disastrous consequences for the organism. Such disorders appear and develop in numerous diseases and accompany these diseases; at the same time, such disorders can play the role of crucial independent pathogenetic factors in the development of one pathology or another.The system of nociception is a part of the total somatosensory system. Similarly to other subdivisions of the somatosensory system, primary afferent neurons and central relay neurons that transmit nociceptive information to the higher CNS "floors" are its input elements. Nociceptors per se, primary sensory structures of certain groups of segmental afferent neurons and afferent neurons of some nuclei of the craniocerebral nerves, constitute primary links in the nociceptive system. Nociceptors differ from other receptor structures of the somatosensory system in their relatively high thresholds for excitation; the generator potential and initiation of impulse activity in these nociceptors are developed only upon the action of stimuli (mechanical, thermal, and chemical) that possess rather high energy and endanger the integrity of the organism and its tissues. This explains, in general, the low modal specificity of nociceptors. Classification of such receptor structures by their modality (mechanonociceptors, thermonociceptors, etc.) is an independent aspect; in our review, we will deal with this aspect only to a limited extent.

Functional imaging within individual pain fibres ex vivo with optical microscopy

“…The nature of the afferent signal depends on a complex interaction between the distribution, density, and biophysical properties of ion channels and molecular transducers present in the afferent terminals, as well as the morphological features of the terminal arbor (Kostyuk and Kostyuk, 2009;Woolf and Ma, 2007). Significant quantitative differences may exist between the patterns of expression of ion channels and signaling systems in the somata and peripheral processes of the afferent neuron.…”

“…Significant quantitative differences may exist between the patterns of expression of ion channels and signaling systems in the somata and peripheral processes of the afferent neuron. Yet, the active membrane properties of the afferent neuron soma and its peripheral terminal endings are most commonly considered identical, and the very real possibility of significant quantitative differences has usually been neglected (Kostyuk and Kostyuk, 2009). High-resolution functional optical imaging in the en bloc dural-skull preparation now provides an opportunity to begin to study the fundamental physiological processes of activation, transduction, sensitization, and propagation of the nociceptive signal in peripheral pain fibre terminations.…”

“…The transient receptor potential vanilloid 1 (TRPV1) receptor/channel is a polymodal sensor and molecular integrator of a wide range of painful stimuli that is activated directly by capsaicin; the natural compound responsible for the sharpness of hot-chili peppers (Caterina et al, 1997;Szallasi et al, 2007). TRPV1 sensitivity to capsaicin is considered a principal pharmacological trait of lightly myelinated A␦-and unmyelinated C-fibre nociceptors and as such, is a hallmark for identifying primary afferent fibres as nociceptors (Kostyuk and Kostyuk, 2009). Ca 2+ transients from the photolysis of the novel and selective TRPV1 custom caged molecule BCMACMOC-caged capsaicin (Gilbert et al, 2007) at the pain fibre ( F/F = 108 ± 48%) as well as the block by the TRPV1 antagonist capsazepine ( F/F = −0.9 ± 0.2%, n = 8) is shown in (Fig.…”

“…Our current understanding of peripheral pain fibre physiology has been almost exclusively derived from research in which electrophysiological recordings were made in the somata of acutely dissociated cell preparations taken from sensory ganglion cells-not from the afferent fibre terminations themselves (Kostyuk and Kostyuk, 2009;Woolf and Ma, 2007). Investigating afferent signaling selectively within pain fibres is challenging because the majority of nociceptors are thin unmyelinated axon fibres that are inaccessible with conventional electrophysiological techniques such as intracellular recording with patch-clamp pipettes.…”

Cation Channels - Molecular Targets for Potential Drugs With an Analgesic Mechanism of Action

“…О.О. Богомольця НАН України зробили значний внесок у вивчення трансмембранної іонної сигналізації та показали можливість іонних каналів брати участь у процесах генерації та передачі больового сигналу [4][5][6]. Саме ці фундаментальні дослідження є підґрунтям для створення лікарських засобів, але у них відсутні пропозиції щодо таких молекул.…”