Neuromodulators can modify the magnitude and kinetics of the response of a sensory neuron to a stimulus. Six neuroactive substances modified the activity of the gastropyloric receptor 2 (GPR2) neuron of the stomatogastric nervous system (STNS) of the crab Cancer borealis during muscle stretch. Stretches were applied to the gastric mill 9 (gm9) and the cardio-pyloric valve 3a (cpv3a) muscles. SDRNFLRFamide and dopamine had excitatory effects on GPR2. Serotonin, GABA, and the peptide allatostatin-3 (AST) decreased GPR2 firing during stretch. Moreover, SDRNFLRFamide and TNRNFLRFamide increased the unstimulated spontaneous firing rate, whereas AST and GABA decreased it. The actions of AST and GABA were amplitude- and history-dependent. In fully recovered preparations, AST and GABA decreased the response to small-amplitude stretches proportionally more than to those evoked by large-amplitude stretches. For large-amplitude stretches, the effects of AST and GABA were more pronounced as the number of recent stretches increased. The modulators that affected the stretch-induced GPR2 firing rate were also tested when the neuron was operating in a bursting mode of activity. Application of SDRNFLRFamide increased the bursting frequency transiently, whereas high concentrations of serotonin, AST, and GABA abolished bursting altogether. Together these data demonstrate that the effects of neuromodulators depend on the previous activity and current state of the sensory neuron.