| Oral clonidine inhibits visceral pain-related viscerosomatic and cardiovascular responses to colorectal distension in rats. | |
| | |
MedLine Citation:
|
PMID: 18593580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The alpha(2)-adrenoceptor agonist, clonidine, modulates colorectal sensorimotor functions in humans and, given intrathecally, has analgesic effects in the colorectal distension (CRD) model in rats. We tested the effects of systemic clonidine on the visceral pain-related viscerosomatic and autonomic cardiovascular responses to CRD and colonic compliance in rats using clinically relevant CRD protocols. The activity of the abdominal musculature (viscerosomatic response), monitored by electromyography and intracolonic manometry, and changes in arterial blood pressure and heart rate, monitored by telemetry, were assessed simultaneously in conscious rats during CRD. Pressure-volume relationships during CRD served as a measure of colonic compliance. Clonidine (50-200 nmol/kg, p.o.) dose-dependently inhibited the viscerosomatic response to phasic, noxious CRD (12 distension at 80 mm Hg). At 200 nmol/kg clonidine also attenuated the increase in blood pressure (70+/-7% inhibition, P<0.05) and heart rate (67+/-16% inhibition, P<0.05) associated to noxious CRD. Similar effects were observed after i.v. administration. Likewise, clonidine (200 nmol/kg, p.o.) reduced the response to ascending phasic CRD (10-80 mm Hg) and significantly increased the threshold pressure for pain-related responses. Clonidine (50 or 150 nmol/kg, i.p.) did not affect the pressure-volume relationship during phasic CRD (2-20 mm Hg). These results show that systemic clonidine, at doses devoid of visible side effects, has analgesic effects in the CRD model of visceral pain in rats without affecting colonic compliance. These observations confirm the analgesic activity of systemic clonidine on visceral pain, support the translational value of the rat CRD model to humans and show that manometry is more sensitive than electromyography detecting pain-related responses. |
| | |
Authors:
|
Mikael Brusberg; Anna Ravnefjord; Magnus Lindgreen; Håkan Larsson; Erik Lindström; Vicente Martinez |
Publication Detail:
|
Type: Journal Article Date: 2008-06-19 |
Journal Detail:
|
Title: European journal of pharmacology Volume: 591 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2008 Sep |
Date Detail:
|
Created Date: 2008-08-12 Completed Date: 2008-10-15 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 243-51 Citation Subset: IM |
Affiliation:
|
AstraZeneca R&D, Integrative Pharmacology - GI Biology, Mölndal, Sweden. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Abdominal Pain
/
drug therapy*,
etiology Analgesics / administration & dosage, pharmacology* Animals Blood Pressure / drug effects Clonidine / administration & dosage, pharmacology* Colonic Diseases / complications, drug therapy* Dilatation, Pathologic / complications, physiopathology Disease Models, Animal Dose-Response Relationship, Drug Electromyography / methods Female Heart Rate / drug effects Humans Manometry / methods Pain Measurement Rats Rats, Sprague-Dawley Sensitivity and Specificity |
| Chemical | |
Reg. No./Substance:
|
0/Analgesics; 4205-90-7/Clonidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The impact of high anxiety level on the oxidative status of mouse peripheral blood lymphocytes, gran...
Next Document: The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxami...