Patel, R;
Dickenson, AH;
(2018)
Modality selective roles of pro-nociceptive spinal 5-HT₂_{A} and 5-HT₃ receptors in normal and neuropathic states.
Neuropharmacology
, 143
pp. 29-37.
10.1016/j.neuropharm.2018.09.028.
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Abstract
Descending brainstem control of spinal nociceptive processing permits a dynamic and adaptive modulation of ascending sensory information. Chronic pain states are frequently associated with enhanced descending excitatory drive mediated predominantly through serotonergic neurones in the rostral ventromedial medulla. In this study, we examine the roles of spinal 5-HT₂_{A} and 5-HT₃ receptors in modulating ascending sensory output in normal and neuropathic states. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus. In sham rats, block of spinal 5-HT₃Rs with ondansetron revealed tonic facilitation of noxious punctate mechanical stimulation, whereas blocking 5-HT₂_{A}Rs with ketanserin had minimal effect on neuronal responses to evoked stimuli. The inhibitory profiles of both drugs were altered in SNL rats; ondansetron additionally inhibited neuronal responses to lower intensity punctate mechanical stimuli and noxious heat evoked responses, whereas ketanserin inhibited innocuous and noxious evaporative cooling evoked responses. Neither drug had any effect on dynamic brush evoked responses nor on spontaneous firing rates in both sham and SNL rats. These data identify novel modality and intensity selective facilitatory roles of spinal 5-HT₂_{A} and 5-HT₃ receptors on sensory neuronal processing within the spinothalamic-somatosensory cortical pathway.
| Type: | Article |
|---|---|
| Title: | Modality selective roles of pro-nociceptive spinal 5-HT₂_{A} and 5-HT₃ receptors in normal and neuropathic states |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuropharm.2018.09.028 |
| Publisher version: | https://doi.org/10.1016/j.neuropharm.2018.09.028 |
| Language: | English |
| Additional information: | © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | In vivo electrophysiology, Ventral posterolateral thalamus, Spinal nerve ligation, Neuropathic pain, Descending facilitation, Serotonergic pain modulation, Ondansetron, Ketanserin, 5-HT₂_{A}, 5-HT₃ |
| 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 |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10056866 |
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