Different roles of two nitric oxide activated pathways in spinal long-term potentiation of C-fiber-evoked field potentials.
There is accumulating evidence implicating the involvement of nitric oxide (NO) in spinal central sensitization. The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of sensitization of nociceptive neurons in the spinal cord. The present study examined the roles of soluble guanylate cyclase (sGC) or ADP-ribosyltransferase (ADPRT), two potential NO targets, in spinal LTP. The results showed that (1) administration of sGC inhibitors, methyl blue (MB, 4mM, 20 microl) or 1H-[1,2,4]oxadiazolo[4,3-a]-quiloxalin-1-one (ODQ, 10 microM, 20 microl) before tetanic stimulation, significantly inhibited the induction of spinal LTP, and this was reversed by 8-Br-cGMP, a membrane-permeable cGMP analog. However, the maintenance of spinal LTP was not changed when application of ODQ 2h after tetanic stimulation. (2) Although our previous experiments have identified a key role for NO in the induction of spinal LTP, NO synthase (NOS) inhibitor, L-NAME (1mM, 20 microl) or hemoglobin (2mg/ml, 20 microl), a scavenger of NO, had no effect on established spinal LTP when applied 2h after the induction of spinal LTP. (3) The mono-ADPRT inhibitor, nicotinamide (10mM, 20 microl), had no effect on the induction and maintenance of spinal LTP. However, the poly-ADPRT inhibitor, benzamide (100 microM, 20 microl), inhibited its maintenance, but not its induction. The results suggest that NO-stimulated guanylyl cyclase activity plays a critical role in the induction of LTP of C-fiber-evoked field potentials in the spinal cord, whereas NO-related poly-ADPRT activity contributes to the maintenance of spinal LTP.
Zhang
Xi-Chun
XC
Institute of Neurobiology, Fudan University, 220 Handan Road, Shanghai 200433, People's Republic of China.
Zhang
Yu-Qiu
YQ
Zhao
Zhi-Qi
ZQ
D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000502:physiology* / Q000528:radiation effects; D006162:Guanylate Cyclase / Q000008:administration & dosage; D007796:Laminectomy / Q000379:methods; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D009412:Nerve Fibers / Q000502:physiology* / Q000528:radiation effects; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D004791:Enzyme Inhibitors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP