title: Delayed stress-induced colonic hypersensitivity in male Wistar rats: role of neurokinin-1 and corticotropin-releasing factor-1 receptors.
abstract: The mechanism(s) underlying stress-induced colonic hypersensitivity (SICH) are incompletely understood. Our aims were to assess the acute and delayed (24 h) effect of water avoidance (WA) stress on visceral nociception in awake male Wistar rats and to evaluate the role of two stress-related modulation systems: the substance P/neurokinin-1 receptor (SP/NK(1)R) and the corticotropin-releasing factor (CRF)/CRF(1) receptor (CRF/CRF(1)R) systems, as well as the possible involvement of the sympathetic nervous system. Visceral pain responses were measured as the visceromotor response to colorectal distension (CRD) at baseline, immediately after WA and again 24 h later. The NK(1)R antagonists RP-67580 and SR-140333 and the CRF(1)R antagonist CP-154526 were injected 15 min before WA or 1 h before the CRD on day 2. Chemical sympathectomy was performed by repeated injection of 6-hydroxydopamine. WA stress resulted in a significant increase in the visceromotor response on day 2, but no change immediately after WA. Injection of CP-154526 abolished delayed SICH when applied either before WA stress or before the CRD on day 2. Both NK(1)R antagonists only decreased SICH when injected before the CRD on day 2. Chemical sympathectomy did not affect delayed SICH. Our results indicate that in male Wistar rats, both NK(1)R and CRF(1)R activation, but not sympathetic nervous system activation, play a role in the development of SICH.
authors: Center for Neurovisceral Sciences and Women's Health, Department of Medicine, David Gaffen School of Medicine ar University of California, Los Angeles 90024, USA.
authors: Ines
authors: I
authors: Schwetz
authors: Sylvie
authors: S
authors: Bradesi
authors: James A
authors: JA
authors: McRoberts
authors: Marciano
authors: M
authors: Sablad
authors: Jerry C
authors: JC
authors: Miller
authors: Huping
authors: H
authors: Zhou
authors: Gordon
authors: G
authors: Ohning
authors: Emeran A
authors: EA
authors: Mayer
mesh_terms: D000818:Animals; D003106:Colon / Q000294:innervation / Q000503:physiopathology*; D004576:Electromyography; D005239:Fear / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000503:physiopathology*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D009619:Nociceptors / Q000502:physiology; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology; D000099052:CRF Receptor, Type 1
chemical_list: C101628:CP 154526; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D011812:Quinuclidines; D018019:Receptors, Corticotropin-Releasing Hormone; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C085215:SR 140333; D000099052:CRF Receptor, Type 1