Document Detail


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.
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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


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