Sikandar, S;
Bannister, K;
Dickenson, AH;
(2012)
Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats.
Neuroscience Letters
, 519
(1)
31 - 36.
10.1016/j.neulet.2012.05.009.
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Abstract
Pro-nociceptive ON-cells in the rostral ventromedial medulla (RVM) facilitate nociceptive processing and contribute to descending serotonergic controls. We use RVM injections of neurotoxic dermorphin-saporin (Derm-SAP) in rats to evaluate the role of putative ON-cells, or μ-opioid receptor-expressing (MOR) neurones, in visceral pain processing. Our immunohistochemistry shows that intra-RVM Derm-SAP locally ablates a substantial proportion of MOR and serotonergic cells. Given the co-localization of these neuronal markers, some RVM ON-cells are serotonergic. We measure visceromotor responses in the colorectal distension (CRD) model in control and Derm-SAP rats, and using the 5-HT(3) receptor antagonist ondansetron, we demonstrate pro-nociceptive serotonergic modulation of visceral nociception and a facilitatory drive from RVM MOR cells. The α(2)δ calcium channel ligand pregabalin produces state-dependent analgesia in neuropathy and osteoarthritis models relating to injury-specific interactions with serotonergic facilitations from RVM MOR cells. Although RVM MOR cells mediate noxious mechanical visceral input, we show that their presence is not a permissive factor for pregabalin analgesia in acute visceral pain.
Type: | Article |
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Title: | Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats. |
Location: | Ireland |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.neulet.2012.05.009 |
Publisher version: | http://dx.doi.org/10.1016/j.neulet.2012.05.009 |
Language: | English |
Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3661978 |
Keywords: | Analgesics, Animals, Brain Stem, Efferent Pathways, Long-Term Potentiation, Male, Nociception, Rats, Rats, Sprague-Dawley, Serotonergic Neurons, Serotonin, Visceral Pain, gamma-Aminobutyric Acid |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
URI: | https://discovery.ucl.ac.uk/id/eprint/1354304 |
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