Papers of the Week

Pain results from the activation of nociceptors following noxious stimuli and evidence shows a link between pain- and stress-related responses in mammalian organisms. In zebrafish, the activation of hypothalamic-pituitary-interrenal (HPI) axis may also regulate the body pigmentation, with camouflage as the primary function. Here, we aimed to investigate a putative relationship between pain-, stress-, and camouflage-related parameters in adult zebrafish. To answer this question, we assessed whether intraperitoneal acetic acid injection can activate the HPI axis by measuring whole-body cortisol and the camouflage response as the main physiological and morphological endpoints in the presence or absence of morphine or naloxone, an opioid antagonist. As indicative of pain, acetic acid induced a stereotypic circling behavior in the top of the tank, accompanied by abdominal writhing-like response, a specific phenotype that reflects local nociceptive effect. Both whole-body cortisol levels and camouflage response increased in the acetic acid group, while morphine prevented these responses and naloxone antagonized morphine-induced effects. Moreover, we observed positive correlations between representative behavioral, physiological, and morphological endpoints measurements and a “pain index” was proposed to summarize the main phenotypic profile of zebrafish under different pharmacological manipulations. Collectively, these findings suggest a coordinated activation of pain, camouflage- and stress-related pathways following acetic acid injection in zebrafish. Our novel data also support that camouflage response represents a novel and relevant biomarker for future assessment of the neural circuitry underlying pain and stress, with a robust sensitivity to opioidergic drugs.