TY - JOUR

T1 - Naloxone prolongs abdominal constriction writhing-like behavior in a zebrafish-based pain model

AU - Costa, Fabiano V.

AU - Canzian, Julia

AU - Stefanello, Flavia V.

AU - Kalueff, Allan V.

AU - Rosemberg, Denis B.

PY - 2019/8/24

Y1 - 2019/8/24

N2 - The ability to detect noxious stimuli is essential to survival. However, pathological pain is maladaptive and severely debilitating. Endogenous and exogenous opioids modulate pain responses via opioid receptors, reducing pain sensibility. Due to the high genetic and physiological similarities to rodents and humans, the zebrafish is a valuable tool to assess pain responses and the underlying mechanisms involved in nociception. Although morphine attenuates pain-like responses of zebrafish, there are no data showing if the antagonism of opioid receptors prolongs pain duration in the absence of an exogenous opioid. Here, we investigated whether a common opioid antagonist naloxone affects the abdominal constriction writhing-like response, recently characterized as a zebrafish-based pain behavior. Animals were injected intraperitoneally with acetic acid (5.0%), naloxone (1.25 mg/kg; 2.5 mg/kg; 5.0 mg/kg) or acetic acid with naloxone to investigate the changes in their body curvature for 1 h. Acetic acid elicited a robust pain-like response in zebrafish, as assessed by aberrant abdominal body curvature, while no effects were observed following PBS injection. Although naloxone alone did not alter the frequency and duration of this behavior, it dose-dependently prolonged acetic acid-induced abdominal curvature response. Besides reinforcing the use of the abdominal writhing-like phenotype as a behavioral endpoint to measure acute pain responses in zebrafish models, our novel data suggest a putative role of endogenous opioids in modulating the recovery from pain stimulation in zebrafish.

AB - The ability to detect noxious stimuli is essential to survival. However, pathological pain is maladaptive and severely debilitating. Endogenous and exogenous opioids modulate pain responses via opioid receptors, reducing pain sensibility. Due to the high genetic and physiological similarities to rodents and humans, the zebrafish is a valuable tool to assess pain responses and the underlying mechanisms involved in nociception. Although morphine attenuates pain-like responses of zebrafish, there are no data showing if the antagonism of opioid receptors prolongs pain duration in the absence of an exogenous opioid. Here, we investigated whether a common opioid antagonist naloxone affects the abdominal constriction writhing-like response, recently characterized as a zebrafish-based pain behavior. Animals were injected intraperitoneally with acetic acid (5.0%), naloxone (1.25 mg/kg; 2.5 mg/kg; 5.0 mg/kg) or acetic acid with naloxone to investigate the changes in their body curvature for 1 h. Acetic acid elicited a robust pain-like response in zebrafish, as assessed by aberrant abdominal body curvature, while no effects were observed following PBS injection. Although naloxone alone did not alter the frequency and duration of this behavior, it dose-dependently prolonged acetic acid-induced abdominal curvature response. Besides reinforcing the use of the abdominal writhing-like phenotype as a behavioral endpoint to measure acute pain responses in zebrafish models, our novel data suggest a putative role of endogenous opioids in modulating the recovery from pain stimulation in zebrafish.

KW - Abdominal constriction writhing-like behavior

KW - Acetic acid

KW - Naloxone

KW - Nociception

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85067894326&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2019.134336

DO - 10.1016/j.neulet.2019.134336

M3 - Article

C2 - 31220523

AN - SCOPUS:85067894326

VL - 708

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

M1 - 134336

ER -