The authors find that the Avpr1a gene, encoding the vasopressin-1A receptor, is responsible for strain-dependent pain sensitivity of mice to formalin and capsaicin. In humans, a single nucleotide polymorphism in AVPR1A was found to affect capsaicin pain and desmopressin analgesia. In both species, the effects were male specific and dependent on stress levels at the time of testing.