• J. Pharmacol. Sci. · Jun 2009

    Protein kinase A-dependence of the supraspinally mediated analgesic effects of gabapentin on thermal and mechanical hypersensitivity.

    • Keiko Takasu, Yu Kinoshita, Hideki Ono, and Mitsuo Tanabe.
    • Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
    • J. Pharmacol. Sci. 2009 Jun 1;110(2):223-6.

    AbstractWe have recently shown that gabapentin generates protein kinase A (PKA)-dependent presynaptic inhibition of GABAergic synaptic transmission in locus coeruleus (LC) neurons only under neuropathic states. To verify behaviorally this in vitro electrophysiological finding, the PKA inhibitor H-89 was injected intracerebroventricularly (i.c.v.) before supraspinal application of gabapentin in mice developing thermal and mechanical hypersensitivity after peripheral nerve injury. H-89 dose-dependently attenuated the analgesic effects of i.c.v.-injected gabapentin, suggesting that PKA-dependent removal of GABAergic inhibition of LC neurons is the most plausible synaptic mechanism underlying the supraspinally mediated analgesic effects of gabapentin involving activation of the descending noradrenergic pain-inhibitory system.

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