当前位置： SCI文献检索 > GASTROENTEROLOGY期刊下所有文献 > Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome.

Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome.

Abstract：

BACKGROUND & AIMS:Narcotic bowel syndrome (NBS) is a subset of opioid bowel dysfunctions that results from prolonged treatment with narcotics and is characterized by chronic abdominal pain. NBS is under-recognized and its molecular mechanisms are unknown. We aimed to (1) develop a rat model of NBS and (2) to investigate its peripheral and central neurobiological mechanisms. METHODS:Male Wistar rats were given a slow-release emulsion that did or did not contain morphine (10 mg/kg) for 8 days. Visceral sensitivity to colorectal distension (CRD) was evaluated during and after multiple administrations of morphine or vehicle (controls). The effects of minocycline (a microglia inhibitor), nor-binaltorphimine (a kappa-opioid antagonist), and doxantrazole (a mast-cell inhibitor) were observed on morphine-induced visceral hyperalgesia. Levels of OX-42, P-p38 mitogen-activated protein kinase, rat mast cell protease II, and protein gene product 9.5 were assessed at different spinal segments (lumbar 6 to sacral 1) or colonic mucosa by immunohistochemistry. RESULTS:On day 8 of morphine administration, rats developed visceral hyperalgesia to CRD (incipient response) that lasted for 8 more days (delayed response). Minocycline reduced the incipient morphine-induced hypersensitivity response to CRD whereas nor-binaltorphimine and doxantrazole antagonized the delayed hyperalgesia. Levels of OX-42 and P-p38 increased in the spinal sections, whereas rat mast cell protease II and protein gene product 9.5 increased in the colonic mucosa of rats that were given morphine compared with controls. CONCLUSIONS:We developed a rat model of narcotic bowel-like syndrome and showed that spinal microglia activation mediates the development of morphine-induced visceral hyperalgesia; peripheral neuroimmune activation and spinal dynorphin release represent an important mechanism in the delayed and long-lasting morphine-induced colonic hypersensitivity response to CRD.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Agostini S,Eutamene H,Cartier C,Broccardo M,Improta G,Houdeau E,Petrella C,Ferrier L,Theodorou V,Bueno L

doi

10.1053/j.gastro.2010.03.046

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

553-63, 563.e1-5

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(10)00471-3

journal_volume

139

pub_type

杂志文章

在线工具

Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome.