Regional anesthesia and pain medicine
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Reg Anesth Pain Med · Jan 2002
Gabapentin decreases membrane calcium currents in injured as well as in control mammalian primary afferent neurons.
Neuropathic pain following injury to peripheral sensory neurons is a common clinical problem and frequently difficult to treat. Gabapentin (GBP), a novel anticonvulsant, has significant analgesic effects in clinical neuropathic states and in relevant preclinical models, but its mechanism of action remains unclear. Because calcium currents play a significant role in neuronal function, this study was designed to assess the effect of GBP on the membrane voltage-activated inward calcium currents (I(Ca)) in dorsal root ganglia (DRG) primary afferent neurons of neuropathic versus control rats. ⋯ GBP, at clinically relevant concentrations, results in significant reduction of I(Ca) in both sham and neuropathic neurons, while in nonoperated rats reduced I(Ca) to a smaller degree. Sensitivity to drug was not affected by neuropathy. This current inhibition is partly voltage dependent. Depression of I(Ca) may be partly related to the binding of the drug to the alpha(2)delta modulatory subunit of the voltage activated calcium channels (VACC). Analgesia may be due to diminished release of neurotransmitter by sensory neurons, a Ca(2+)-dependent process.