Induction of long-term potentiation in single nociceptive dorsal horn neurons is blocked by the CaMKII inhibitor AIP.
Neuronal events leading to development of long-term potentiation (LTP) in the nociceptive pathways may be a cellular mechanism underlying central hyperalgesia. Here, we examine whether induction of LTP in nociceptive dorsal horn neurons at depths of 80-500 microm from the cord surface can be affected by spinal application of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor AIP. Extracellular recordings from single neurons in intact urethane anesthetized Sprague-Dawley rats were performed, and the neuronal A-fiber and C-fiber responses after sciatic nerve test pulses were defined according to latencies. A clear LTP of the nociceptive transmission following sciatic nerve high-frequency stimulation (HFS) was observed in single neurons in laminae I-IV of the dorsal horn. The increase in the C-fiber response after HFS was blocked in the presence of 2.0 mM AIP (P < 0.05 HFS group versus AIP + HFS group 2 h after conditioning). However, the C-fiber response was not affected by 2.0 mM AIP alone or by vehicle. Thus, our data show that the neuronal process leading to the induction of LTP in the dorsal horn induced by HFS is clearly inhibited by the specific CaMKII inhibitor AIP. It is concluded that CaMKII may be important for the induction of LTP in single nociceptive dorsal horn neurons.
Pedersen
Linda Margareth
LM
National Institute of Occupational Health, Department of Physiology, Pb 8149 Dep, N-0033 Oslo, Norway. linda.m.pedersen@stami.no
Lien
Guro Flor
GF
Bollerud
Ingunn
I
Gjerstad
Johannes
J
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009619:Nociceptors / Q000187:drug effects* / Q000201:enzymology; D010455:Peptides / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology
C503464:CaMKII inhibitor AIP; D010455:Peptides; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases