The generation and use of disease models in fish such as zebrafish are provided, in particular use in a screen to identify a gene or test substance that affects a disease state associated with pain or nociception, or pain or nociception. In particular, fish models are used in a screen to identify a gene or test substance that affects activity or effect of a second gene provided transgenically that affects a pain or nociception state of the fish, or a treatment of the fish that affects a pain or nociception state of the fish. A pain state or nociception of model fish is compared with that of mutated or treated fish, allowing for identification of genes and test substances with therapeutic application.