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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-irinitrobenzene 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 µL of 35% ethanol). TNBS (0.5 mg) induced referred mechanical hyperalgesia in the abdomen (response frequencies at 24 h: saline 11.0% [+ or -] 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 ([ET.sub.A] 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 ([ET.sub.B] 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 [ET.sub.A] receptor-signaled mechanisms. Key words: colitis, TNBS, mice, endothelin. [ET.sub.A] and [ET.sub.B] receptors. On a examine la contribution de l'endoiheline aux modifications de sensibilite a une stimulation mecanique de l'abdomen inferieur et de la patte arriere durant une colite induite par le TNBS. On a evalue la frequence des reactions de retrait a 10 applications successives d'une sonde de von Frey sur la partie inferieure de l'abdomen (0,07 g) ou le dessous de la patte arriere (0,4 g) de souris BALB/c males, avant et apres une injection intracolique de TNBS (0.5, 1,0, ou 1.5 mg dans 100 µL d'ethanol 35 %). Le TNBS (0,5 mg) a provoque une hyperalgesie mecanique projetee dans l'abdomen (frequence des reponses a 24 h: solution salee 11,0% ± 3,1 %, TNBS 48,0 % ± 6,9%) et la patte arriere (frequence a 24 h: solution salee 12,5% ± 4,7%, TNBS 47,1 % [+ or -] 7,1 %), qui a dure jusqu'a 72 h et 48 h, respectivement. Les souris ayant recu 1 ou 1,5 mg de TNBS ont adopte une posture voutee et se sont immobilisees durant la stimulation mecanique, ce qui laisse supposer une douleur continue excessive. L'atrasentan (antagoniste des recepteurs [ET.sub.A] ; 10 et 30 mg/kg, i.v.), administre 24 h apres le TNBS, a supprime l'hyperalgesie mecanique dans la patte arriere et l'abdomen pendant 2 a 3 h. L'A-192621 (antagoniste des recepteurs [ET.sub.B]; 20 mg/kg, i.v.) a attenue l'hyperalgesie mecanique abdominale a 3 h seulement. Ainsi, les endolhelines contribuent de maniere significative a l'hyperalgesie mecanique projetee dans l'abdomen et la patte arriere durant une colite induite par le TNBS, principalement par des mecanismes vehicules par les recepteurs [ET.sub.A]. Mou-cles : colite, TNBS, souris, endotheline, recepteurs [ET.sub.A] et [ET.sub.B]. [Traduit par la Redaction], Introduction Pain of visceral origin represents one of the most common causes leading patients to seek medical attention. Current knowledge about the mechanisms of visceral-related pain is limited, mainly because [...]

Blockade of central endothelin E[T.sub.B] receptors inhibits fever induced by LPS in conscious rats. The contribution of E[T.sub.B] receptor-mediated mechanisms to fever triggered by intracerebroventricular IL-6, PG[E.sub.2], PG[F.sub.2[alpha]], corticotropin-releasing factor (CRF), and preformed pyrogenic factor derived from LPS-stimulated macrophages (PFPF) was examined. The influence of natural IL-1 receptor antagonist or soluble TNF receptor I on endothelin (ET)-1-induced fever was also assessed. The selective [ET.sub.B] receptor antagonist BQ-788 (3 pmol icv) abolished fever induced by intracerebroventricular ET-1 (1 pmol) or PFPF (200 ng) and reduced that caused by ICV CRF (1 nmol) but not by IL-6 (14.6 pmol), PG[E.sub.2] (1.4 nmol), or PG[F.sub.2[alpha]], (2 nmol). CRF-induced fever was also attenuated by bosentan (dual [ET.sub.A]/[ET.sub.B] receptor antagonist; 10 mg/kg iv) but unaffected by BQ-123 (selective [ET.sub.A] receptor antagonist; 3 pmol icy). [alpha]-Helical [CRF.sub.9-41] (dual [CRF.sub.1]/[CRF.sub.2] receptor antagonist; 6.5 nmol icy) attenuated fever induced by CRF but not by ET-1. Human IL-1 receptor antagonist (9.1 pmol) markedly reduced fever to IL-1[beta] (180 pmol) or ET-1 and attenuated that caused by PFPF or CRF. Murine soluble TNF receptor I (23.8 pmol) reduced fever to TNF-[alpha] (14.7 pmol) but not to ET-1. The results of the present study suggest that PFPF and CRF recruit the brain ET system to cause [ET.sub.B] receptor-mediated IL-1-dependent fever. prostaglandins; cytokines; interleukin-1 receptor antagonist