Measurement of visceral sensitivity in animals is mainly based on 'pseudoaffective' responses, which are brain stem reflexes. For example, in female, but not male rats, acute partial restraint stress induces hypersensitivity to colorectal distension. Mucosal mast cell density increases in rats after nematode infection or maternal deprivation, and both also induce colon hypersensitivity. Significantly, the proximity between nerves and mast cells has been found to be increased in adult rats submitted to maternal deprivation. Protease activation of the proteinase-activated receptor-2 also increases visceral nociception in rats, suggesting that an increase in paracellular permeability may be the primum movens in several animal models of visceral hypersensitivity. Accumulating evidence suggests that sensitization of visceral afferents is not restricted to the presumed nociceptor population, suggesting that most of the mechanosensitive afferent population can contribute to visceral discomfort and pain. Other inflammation-produced changes (e.g. subunit composition of purine-gated P2X channels) in visceral sensory neurones may also contribute to visceral hypersensitivity. This article discusses use of in vivo strategies (and transgenic mouse models) to reveal putative roles in mechanosensitivity and sensitization for molecules not previously considered to have mechanosensory functions.