No NO, no pain? The role of nitric oxide and cGMP in spinal pain processing.
A large body of evidence indicates that nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) essentially contribute to the processing of nociceptive signals in the spinal cord. Many animal studies have unanimously shown that inhibition of NO or cGMP synthesis can considerably reduce both inflammatory and neuropathic pain. However, experiments with NO donors and cGMP analogs also caused conflicting results because dual pronociceptive and antinociceptive effects of these molecules have been observed. Here, we summarize the most recent advances in the understanding of NO- and cGMP-dependent signaling pathways in the spinal cord and further unravel the role of NO and cGMP in pain processing.
Schmidtko
Achim
A
Pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany. schmidtko@em.uni-frankfurt.de
Tegeder
Irmgard
I
Geisslinger
Gerd
G
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D060588:LIM Domain Proteins; D008959:Models, Neurological; D009569:Nitric Oxide / Q000502:physiology*; D010146:Pain / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C486176:CRIP2 protein, human; D060588:LIM Domain Proteins; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP