Protein Kinase A–Dependence of the Supraspinally Mediated Analgesic Effects of Gabapentin on Thermal and Mechanical Hypersensitivity

Journal of Pharmacological Sciences

Hideki Ono¹  Yu Kinoshita¹  Mitsuo Tanabe¹  Keiko Takasu¹ 

[1] Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan

关键词: neuropathic pain;    gabapentin;    protein kinase A (PKA);   

DOI  :  10.1254/jphs.09091SC

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(15)Cited-By(8)We 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.

【 授权许可】

Unknown