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Intestinal anti‐nociceptive behaviour of NK 3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of action
Author(s) -
Fioramonti J.,
Gaultier E.,
Toulouse M.,
Sanger G. J.,
Bueno L.
Publication year - 2003
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1046/j.1365-2982.2003.00420.x
Subject(s) - nociception , medicine , distension , receptor , visceral pain , peripheral , antagonism , endocrinology , anesthesia
The involvement of neurokinin receptors in visceral nociception is well documented. However, the role and localization of NK 3 receptors is not clearly established. This study was designed to determine whether NK 3 receptor antagonists crossing (talnetant) or not (SB‐235375) the blood–brain barrier reduce the nociceptive response to colo‐rectal distension (CRD) and whether NK 3 antagonism reduces inflammation‐ or stress‐induced hypersensitivity to rectal distension. Isobaric CRD and isovolumic rectal distensions were performed in rats equipped with intramuscular electrodes to record abdominal muscle contractions. In controls, CRD induced a pressure‐related (15–60 mmHg) increase in the number of abdominal contractions. Both talnetant and SB‐235375 [50 mg kg −1 , per oral (p.o.)], which had no effect on colo‐rectal tone, reduced the number of contractions associated with CRDs from 30 to 60 mmHg. Three days after rectal instillation of TNBS, abdominal contractions were increased for rectal distension volume of 0.4 mL. This effect was not modified by talnetant (30 mg kg −1 , p.o.). Partial restraint stress increased abdominal contractions at all distension volumes (0–1.2 mL). Talnetant (10 mg kg −1 , p.o.) abolished the increase observed for 0.8 and 1.2 mL. These results indicate that peripheral NK 3 receptor antagonism reduced nociception associated with CRD and hypersensitivity induced by stress but not inflammation.