Effects of Gabapentin on Calcium Transients in Neurons of the Rat Dorsal Root Ganglia

2009

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We studied the effect of gabapentin (an agent similar, in its molecular structure, to gamma-aminobutyric acid, GABA) on depolarization-evoked calcium transients in small, mid-sized, and large (diameter of the soma up to 25, 25 to 35, and 35 μm or more, respectively) neurons of the dorsal-root ganglia (DRGs) of rats with experimental streptozotocin-induced diabetes mellitus. These transients were measured using a calcium-sensitive fluorescent dye, Fura 2/AM. The amplitude of calcium transients in rats with diabetes was somewhat higher than that in healthy animals (in large and mid DRG neurons by nearly 12% and in small cells by about 8%, on average). The development of diabetes led to a dramatic increase in the total duration of such transients. In large, mid, and small DRG neurons, the values of this parameter in animals with diabetes were, respectively, about 260, 430, and 250% as compared with the norm. The duration of transients at the level of 50% amplitude (Т 0.5 ) in diabetes changed to a significantly smaller extent. Applications of gabapentin (25 μM) led to a decrease in the amplitude of calcium transients, their full duration, and Т 0.5 . The effects of gabapentin were the strongest in large DRG neurons where the amplitude of calcium transients dropped by nearly 36%, while the total duration demonstrated a more than threefold decrease. Upon the action of gabapentin, the parameter Т 0.5 changed moderately (in all groups of DRG neurons, the decrease varied from 8 to 12%). Gabapentin-induced decreases in the amplitude of calcium transients differed in various subgroups of DRG neurons. Among neurons with mid-sized somata, the decrease in this parameter in capsaicin-positive cells was 16.3%, while that in capsaicin-negative cells reached 36.7%. The obtained data are indicative of the ability of gabapentin to normalize, to a certain extent, the parameters of diabetes-modified calcium transients in DRG neurons. This ability is more clearly pronounced in large neurons (we hypothesize that a part of such cells in animals with diabetes are, probably, abnormally involved in transmission of nociceptive influences) and also in a part of mid-sized DRG neurons participating in the formation of acute pain sensation.

Section: Resultsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

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Effects of Gabapentin on Different Neuronal Populations in the Dorsal-Root Ganglia of Rats with Streptozotocin-Induced Diabetes Mellitus

Romanenko

2009

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

2009

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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.

Activity of TRPV1 Channels in Primary Nociceptive Neurons of Rats: Modulation by Changes in Intracellular Calcium Level

Romanenko

2009

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In rat neurons of the dorsal root ganglia (DRG) with mid-(35 to 25 µm) and small-sized (less than 25 µm) somata, we studied calcium transients induced by application of capsaicin (selective agonist of TRPV1 channels) under conditions of the development of other calcium transients caused by preliminary depolarization of the plasma membrane of these neurons. The above transients in rat DRG neurons were measured using the calcium-sensitive fluorescent dye Fura 2/AM. At delays of 3, 7, and 10 sec with respect to the beginning of preliminary potassium depolarization, the amplitudes of capsaicin-induced responses were smaller, as compared with the control, on average, by 26.8, 22.1, and 4.5%, respectively, in the population of mid-sized neurons and by 35.3, 21.1, and 22.4% in small neurons. Under such conditions, we observed noticeable delays of reactions to applications of capsaicin and a certain decrease in the level of intracellular calcium at the moment of beginning of development of these reactions with respect to the corresponding values in isolated depolarization-induced transients. We conclude that excitation of primary nociceptive neurons and activation of voltage-operated calcium channels result in noticeable modulation of the activity of TRPV1 channels and change their role during pain reception.