Peripheral injection of sauvagine prevents repeated colorectal distension-induced visceral pain in female rats.
We investigated the effects of peripheral injection of sauvagine, a CRF2>CRF1 receptor (corticotropin-releasing factor) agonist compared with CRF, on two sets of tonic colorectal distension (CRDs 30, 40, 50 mmHg, 3-min on/off)-induced visceromotor response (VMR) measured as area under the curve (AUC) of abdominal muscle contraction in conscious female rats. Sauvagine (10 or 20 microg/kg, s.c.) abolished the 226.7+/-64.3% and 90.4+/-38.1% increase in AUC to the 2nd CRD compared with the 1st CRD (performed 30 min before) in female Fisher and Sprague-Dawley (SD) rats, respectively. CRF had no effect while the CRF1 antagonist, antalarmin (20 mg/kg, s.c.), alone or with sauvagine, blocked the enhanced response to the 2nd CRD, performed 60 min after the 1st CRD, and reduced further the AUC by 33.5+/-23.3% and 63.5+/-7.2%, respectively in Fisher rats. These data suggest that peripheral CRF2 receptor activation exerts antinociceptive effects on CRD-induced visceral pain, whereas CRF1 contributes to visceral sensitization.
Million
Mulugeta
M
Center for Neurovisceral Sciences and Women's Health, Division of Digestive Diseases, Department of Medicine, University of California Los Angeles, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA. mmuluget@ucla.edu
Maillot
Céline
C
Adelson
David A
DA
Nozu
Tsukasa
T
Gauthier
Ariane
A
Rivier
Jean
J
Chrousos
George P
GP
Bayati
Alfred
A
Mattsson
Hillevi
H
Taché
Yvette
Y
D015746:Abdominal Pain / Q000209:etiology / Q000517:prevention & control*; D029845:Amphibian Proteins; D000818:Animals; D003106:Colon / Q000503:physiopathology*; D004108:Dilatation, Pathologic; D005260:Female; D007279:Injections, Subcutaneous; D009119:Muscle Contraction; D036361:Peptide Hormones; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors; D012007:Rectum / Q000503:physiopathology*
D029845:Amphibian Proteins; D036361:Peptide Hormones; D010455:Peptides; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; C025727:sauvagine