NOS1 and irritable bowel syndrome: In rat models, antinociceptive effect of NO pathways on visceral hypersensitivity has been shown.70,71 For example, Shamshiri et al. demonstrated that lithium inhibited visceral hypersensitivity in a rat model with acetic acid-induced colitis and that the effect was lowered by NOS inhibitors, suggesting the antinociceptive effect of NO pathway in visceral hypersensitivity.72 In contrast, in a randomized controlled study, NOS inhibitor increased the threshold for discomfort/pain in IBS patients.73 This conflicting data may derive from differences between subjects.