Cyclic GMP pathway is critical for inducing long-term sensitization of nociceptive sensory neurons

Noxious stimulation can trigger persistent sensitization of somatosensory s ystems that involves memory-like mechanisms. Here we report that noxious st imulation of the mollusc Aplysia produces transcription-dependent, long-ter m hyperexcitability (LTH) of nociceptive sensory neurons that requires a ni tric oxide (NO)-cyclic GMP-protein kinase C (PKG) pathway. Injection of cGM P induced LTH, whereas antagonists of the NO-cGMP-PKG pathway prevented pin ch-induced LTH. Co-injection of calcium/cAMP-responsive-element (CRE) block ed 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 path way and at least one other pathway, but not the cAMP-PKA pathway, are criti cal for inducing LTH after brief, noxious stimulation.