Endothelin-1-induced nociception

• Published in: Life sciences (1973) Vol. 49; no. 11; p. PL61
• Main Authors: Raffa, R B, Schupsky, J J, Martinez, R P, Jacoby, H I
• Format: Journal Article
• Language: English
• Published: Netherlands 1991
• Subjects: Animals; Endothelins - pharmacology; Endothelins - therapeutic use; Male; Mice; Morphine - pharmacology; Naloxone - pharmacology; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Pain - drug therapy; Pain Measurement
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(91)90252-7

Intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of morphine to mice antagonized the abdominal constriction induced by an i.p. injection of endothelin-1 (ET-1; 0.1 mg/kg). The ED50 values (95% confidence intervals) were 39.3 (16.5-80.2) ng and 1.5 (0.8-4.9) ng, respectively. The antagonism of ET-1-induced abdominal constriction by morphine was blocked by naloxone (1.0 mg/kg, s.c.) or by 24 h pretreatment with beta-funaltrexamine (beta-FNA; 8.84 micrograms, i.c.v.). These results demonstrate for the first time that the stimulus resulting from an i.p. injection of ET-1 is transmitted via ascending (pain) pathways that are subject to attenuation by opioid (mu) receptor activation. Hence, ET-1-induced abdominal constriction is a new pain model which, given the other pharmacology of ET-1, might represent a unique model with potential specific utility for anginal or other visceral pain.