Understanding nociception-related phenotypes in adult zebrafish: Behavioral and pharmacological characterization using a new acetic acid model.

Pain, a severely debilitating symptom of many human disorders, is a growing, unmet biomedical problem. Although the use of zebrafish (Danio rerio) to investigate both behavioral and physiological nociception-related responses is expanding rapidly, the characterization of behavioral phenotypes that reflect injury location is limited, making the results of such studies difficult to interpret. Here, we characterize putative nociception-related behavioral phenotypes in adult zebrafish following an intraperitoneal (i.p.) administration of acetic acid, a well-established protocol for visceral pain in rodents. Acetic acid (2.5 and 5.0%) induced an abdominal constriction-like response, which was assessed by measuring a body curvature index. Moreover, all doses tested (0.5-5.0%) reduced distance traveled and vertical activity in the novel tank test. Freezing duration increased following 5.0% acetic acid, whereas fish injected with 1.0, 2.5, and 5.0% spent more time in top area of the tank. Both morphine (an opioid analgesic) and diclofenac (a nonsteroidal anti-inflammatory drug, NSAID) prevented the 5.0% acetic acid-induced changes in body curvature index, whereas naloxone blocked these effects of morphine. Overall, zebrafish exposed to a single acetic acid i.p. injection display abnormal body curvature and specific changes in behavioral parameters sensitive to anti-nociceptive pharmacological modulation. We suggest that the abdominal constriction-like response represents a novel specific nociceptive-related phenotype in zebrafish. In general, our findings support the growing utility of zebrafish in translational pain research and antinociceptive drug discovery.