کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6262361 | 1292351 | 2016 | 14 صفحه PDF | دانلود رایگان |
- Ca2+-imaging was used to study the spinal effect of pregabalin in adult rats.
- Clinically relevant concentration of pregabalin had no acute inhibitory effect.
- Extremely high concentration of pregabalin slightly inhibited neuronal activity.
- The effects of pregabalin were similar in normal and diabetic neuropathic rats.
- Acute spinal effect of pregabalin may not be its main analgesic mechanism.
Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δâ1 subunits of voltage-gated calcium (Ca2+) channels. However, the exact analgesic mechanism after its binding to α2δâ1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (â10 μM) 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 μM) and a very high concentration of pregabalin (100 μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca2+ signals, whereas an extremely high dose of pregabalin (300 μM) 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.
Journal: Brain Research - Volume 1648, Part A, 1 October 2016, Pages 445-458