Endothelins implicated in referred mechanical hyperalgesia associated with colitis induced by TNBS in mice.
This study evaluated the contribution of endothelins to changes in sensitivity to mechanical stimulation of the lower abdomen and hind paw associated with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. The frequency of withdrawal responses to 10 consecutive applications of von Frey probes to the lower abdomen (0.07 g) or hind paw (0.4 g) was assessed in male BALB/c mice before and after intracolonic TNBS injection (0.5 mg in 100 microL of 35% ethanol). TNBS (0.5 mg) induced referred mechanical hyperalgesia in the abdomen (response frequencies at 24 h: saline 11.0% +/- 3.1%, TNBS 48.0% +/- 6.9%) and hind paw (frequencies at 24 h: saline 12.5% +/- 4.7%, TNBS 47.1% +/- 7.1%) lasting up to 72 and 48 h, respectively. Mice receiving 1.0 or 1.5 mg TNBS assumed hunch-backed postures and became immobile during abdominal mechanical stimulation, suggestive of excessive ongoing pain. Atrasentan (ETA receptor antagonist; 10 and 30 mg/kg, i.v.) given 24 h after TNBS abolished hind paw and abdominal mechanical hyperalgesia for 2-3 h. A-192621 (ETB receptor antagonist; 20 mg/kg, i.v.) attenuated abdominal mechanical hyperalgesia at the 3 h time point only. Thus, endothelins contribute importantly to abdominal and hind paw referred mechanical hyperalgesia during TNBS-induced colitis mainly through ETA receptor-signaled mechanisms.
Claudino
Rafaela Franco
RF
Department of Pharmacology, Biological Sciences Center, Universidade Federal de Santa Catarina, Florianopolis, SC 88049-900, Brazil.
Marcon
Rodrigo
R
Bento
Allisson Freire
AF
Chichorro
Juliana Geremias
JG
Rae
Giles Alexander
GA
D015746:Abdominal Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000077868:Atrasentan; D003092:Colitis / Q000139:chemically induced* / Q000150:complications*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D005528:Foot / Q000294:innervation / Q000503:physiopathology; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D053591:Referred Pain / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000627:therapeutic use; D014110:Touch; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage / Q000494:pharmacology
C120508:A 192621; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins; D011759:Pyrrolidines; D009020:Morphine; D014302:Trinitrobenzenesulfonic Acid; D000077868:Atrasentan