| Endogenous neurotensin facilitates visceral nociception and is required for stress-induced antinociception in mice and rats. | |
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MedLine Citation:
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PMID: 15207335 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Central neurotensin (NT) administration can both facilitate and inhibit somatic and visceral nociception, depending on the dose and administration site. NT microinjection in the rostroventral medulla facilitates nociception at low doses, while NT antagonist microinjection can markedly attenuate nociception, supporting the hypothesis that endogenous NT facilitates nociception. However, higher doses of NT produce a mu-opioid receptor-independent analgesia, similar to that resulting from various intense stressors. Furthermore, intense stress results in increased NT expression in several hypothalamic nuclei that have been implicated in stress-induced antinociception (SIAN); however, there is little direct evidence that endogenous NT is required for SIAN. We have investigated the role of endogenous NT in both basal visceral nociception and SIAN using both NT knockout mice and pharmacological approaches in rats. Visceral nociception was monitored by measuring visceromotor responses during colorectal distension both prior to and following water avoidance stress. Visceral nociception was significantly attenuated in both NT knockout mice and rats pre-treated with the NT antagonist SR 48692. Disruption of NT signaling also blocked SIAN, revealing a novel stress-induced hyperalgesic response that was significantly greater in female than in male rats. NT was also required for acetic acid-induced hyperalgesia. These results indicate that endogenous NT normally facilitates visceral pain responses, is required for irritant-induced hyperalgesia, and plays a critical role in SIAN. |
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Authors:
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X Gui; R E Carraway; P R Dobner |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Neuroscience Volume: 126 ISSN: 0306-4522 ISO Abbreviation: Neuroscience Publication Date: 2004 |
Date Detail:
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Created Date: 2004-06-21 Completed Date: 2004-10-08 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 1023-32 Citation Subset: IM |
Copyright Information:
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Copyright 2004 IBRO |
Affiliation:
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Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Balloon Dilatation Behavior, Animal Colon / innervation, physiology Electromyography Female Hyperalgesia / chemically induced, prevention & control Male Mice Mice, Inbred C57BL Mice, Knockout Neurotensin / pharmacology* Nociceptors / drug effects* Pain Measurement / drug effects Physical Stimulation Pyrazoles / therapeutic use Quinolines / therapeutic use Rats Rats, Sprague-Dawley Receptors, Neurotensin / antagonists & inhibitors Rectum / innervation, physiology Sex Characteristics Stress, Physiological / physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
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5P30 DK32520/DK/NIDDK NIH HHS; DK28565/DK/NIDDK NIH HHS; DK99004/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Pyrazoles; 0/Quinolines; 0/Receptors, Neurotensin; 146362-70-1/SR 48692; 39379-15-2/Neurotensin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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