Cyclic GMP pathway is critical for inducing long-term sensitization of nociceptive sensory neurons.
Noxious stimulation can trigger persistent sensitization of somatosensory systems that involves memory-like mechanisms. Here we report that noxious stimulation of the mollusc Aplysia produces transcription-dependent, long-term hyperexcitability (LTH) of nociceptive sensory neurons that requires a nitric oxide (NO)-cyclic GMP-protein kinase G (PKG) pathway. Injection of cGMP induced LTH, whereas antagonists of the NO-cGMP-PKG pathway prevented pinch-induced LTH. Co-injection of calcium/cAMP-responsive-element (CRE) blocked both pinch-induced LTH and cAMP-induced LTH, but antagonists of protein kinase A (PKA) failed to block pinch-induced LTH. Thus the NO-cGMP-PKG pathway and at least one other pathway, but not the cAMP-PKA pathway, are critical for inducing LTH after brief, noxious stimulation.
Lewin
M R
MR
Department of Integrative Biology, Physiology and Pharmacology, University of Texas-Houston 77030, USA.
Walters
E T
ET
D000818:Animals; D001048:Aplysia; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D010812:Physical Stimulation; D011494:Protein Kinases / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011494:Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester