Effects of Gabapentin on Different Neuronal Populations in the Dorsal-Root Ganglia of Rats with Streptozotocin-Induced <Emphasis Type="Italic">Diabetes Mellitus</Emphasis> |
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Authors: | S V Romanenko P G Kostyuk E P Kostyuk |
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Institution: | 1.International Center for Molecular Physiology,National Academy of Sciences of Ukraine,Kyiv,Ukraine;2.Bogomolets Institute of Physiology,National Academy of Sciences of Ukraine,Kyiv,Ukraine |
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Abstract: | 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. |
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