Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats.

Neuroscience Letters
Shafaq SikandarAnthony H Dickenson

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.

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Citations

Apr 14, 2016·Pharmacology Research & Perspectives·Ryan Patel, Anthony H Dickenson
Jan 18, 2015·European Journal of Pharmacology·Sergey S PanteleevOlga А Lyubashina
Oct 18, 2016·European Journal of Pain : EJP·D ReissC Gavériaux-Ruff
May 13, 2017·Expert Review of Medical Devices·Timothy R DeerJason E Pope
Jul 20, 2017·Physiological Reports·Shafaq SikandarAnthony H Dickenson
Mar 12, 2019·Current Opinion in Supportive and Palliative Care·Kristian K PetersenThomas Graven-Nielsen
Mar 15, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Beverley Greenwood-Van MeerveldAnthony C Johnson
Jul 24, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·K Bannister, A H Dickenson

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