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Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome.
Gastroenterology. 2010 Aug; 139(2):553-63, 563.e1-5.G

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.

Authors+Show Affiliations

INRA, EI-Purpan, UMR 1054 Neuro-Gastroenterology and Nutrition, Toulouse, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20347820

Citation

Agostini, Simona, et al. "Evidence of Central and Peripheral Sensitization in a Rat Model of Narcotic Bowel-like Syndrome." Gastroenterology, vol. 139, no. 2, 2010, pp. 553-63, 563.e1-5.
Agostini S, Eutamene H, Cartier C, et al. Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome. Gastroenterology. 2010;139(2):553-63, 563.e1-5.
Agostini, S., Eutamene, H., Cartier, C., Broccardo, M., Improta, G., Houdeau, E., Petrella, C., Ferrier, L., Theodorou, V., & Bueno, L. (2010). Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome. Gastroenterology, 139(2), 553-63, e1-5. https://doi.org/10.1053/j.gastro.2010.03.046
Agostini S, et al. Evidence of Central and Peripheral Sensitization in a Rat Model of Narcotic Bowel-like Syndrome. Gastroenterology. 2010;139(2):553-63, 563.e1-5. PubMed PMID: 20347820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome. AU - Agostini,Simona, AU - Eutamene,Helene, AU - Cartier,Christel, AU - Broccardo,Maria, AU - Improta,Giovanna, AU - Houdeau,Eric, AU - Petrella,Carla, AU - Ferrier,Laurent, AU - Theodorou,Vassillia, AU - Bueno,Lionel, Y1 - 2010/03/25/ PY - 2009/12/18/received PY - 2010/03/08/revised PY - 2010/03/15/accepted PY - 2010/3/30/entrez PY - 2010/3/30/pubmed PY - 2010/8/13/medline SP - 553-63, 563.e1-5 JF - Gastroenterology JO - Gastroenterology VL - 139 IS - 2 N2 - 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. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/20347820/Evidence_of_central_and_peripheral_sensitization_in_a_rat_model_of_narcotic_bowel_like_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(10)00471-3 DB - PRIME DP - Unbound Medicine ER -