Journal
BRAIN RESEARCH
Volume 1648, Issue -, Pages 445-458Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2016.08.018
Keywords
Ca2+-imaging; Pregabalin; Clinically relevant concentration; Acute effect; Spinal cord; Diabetic neuropathic rat
Categories
Funding
- Japan Society for the Promotion of Science [15590190, 20590218]
- Grants-in-Aid for Scientific Research [15590190, 20590218] Funding Source: KAKEN
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Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to alpha 2 delta - 1 subunits of voltage-gated calcium (Ca2+) channels. However, the exact analgesic mechanism after its binding to alpha 2 delta - 1 subunits remains largely unknown. Whether a clinical concentration of pregabalin ( 10 uM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca2+-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca2+ signals predominantly in the superficial dorsal horn. Clinically relevant (10 mu M) and a very high concentration of pregabalin (100 pM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca2+ signals, whereas an extremely high dose of pregabalin (300 mu M) slightly but significantly attenuated Ca2+ signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. (C) 2016 Elsevier B.V. All rights reserved.
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