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Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome.
- Source :
-
Gastroenterology [Gastroenterology] 2010 Aug; Vol. 139 (2), pp. 553-63, 563.e1-5. Date of Electronic Publication: 2010 Mar 25. - Publication Year :
- 2010
-
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.<br />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.<br />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.<br />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.<br /> (Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Abdominal Pain chemically induced
Abdominal Pain metabolism
Animals
CD11b Antigen metabolism
Chymases metabolism
Colon drug effects
Colon metabolism
Delayed-Action Preparations
Disease Models, Animal
Hyperalgesia chemically induced
Hyperalgesia metabolism
Immunohistochemistry
Intestinal Mucosa innervation
Male
Mast Cells metabolism
Microglia metabolism
Minocycline pharmacology
Morphine
Naltrexone analogs & derivatives
Naltrexone pharmacology
Narcotic Antagonists pharmacology
Pain Measurement
Pressure
Rats
Rats, Wistar
Spinal Cord drug effects
Spinal Cord metabolism
Syndrome
Thioxanthenes pharmacology
Time Factors
Ubiquitin Thiolesterase metabolism
Xanthones pharmacology
p38 Mitogen-Activated Protein Kinases metabolism
Abdominal Pain physiopathology
Colon innervation
Gastrointestinal Transit drug effects
Hyperalgesia physiopathology
Pain Threshold drug effects
Spinal Cord physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 139
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 20347820
- Full Text :
- https://doi.org/10.1053/j.gastro.2010.03.046