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Da Vitoria Lobo, ME, Madden, R, Liddell, S, Hirashima, M and Hulse, RP 
ORCID: https://orcid.org/0000-0002-5193-9822,
2023.
Spinal cord vascular degeneration impairs duloxetine penetration.
Frontiers in Pain Research, 4: 1190440.
ISSN 2673-561X
Abstract
Introduction: Chronic pain is a prevalent physically debilitating health-related morbidity. Frontline analgesics are inadequate, providing only partial pain relief in only a proportion of the patient cohort. Here, we explore whether alterations in spinal cord vascular perfusion are a factor in reducing the analgesic capability of the noradrenaline reuptake inhibitor, duloxetine.
Method: An established rodent model of spinal cord vascular degeneration was used. Endothelial-specific vascular endothelial growth factor receptor 2 knockout mouse was induced via hydroxytamoxifen administered via intrathecal injection. Duloxetine was administered via intraperitoneal injection, and nociceptive behavioural testing was performed in both WT and VEGFR2KO mice. LC-MS/MS was performed to explore the accumulation of duloxetine in the spinal cord in WT and VEGFR2KO mice.
Results: Spinal cord vascular degeneration leads to heat hypersensitivity and a decline in capillary perfusion. The integrity of noradrenergic projections (dopa - hydroxylase labelled) in the dorsal horn remained unaltered in WT and VEGFR2KO mice. There was an association between dorsal horn blood flow with the abundance of accumulated duloxetine in the spinal cord and analgesic capacity. In VEGFR2KO mice, the abundance of duloxetine in the lumbar spinal cord was reduced and was correlated with reduced anti-nociceptive capability of duloxetine.
Discussion: Here, we show that an impaired vascular network in the spinal cord impairs the anti-nociceptive action of duloxetine. This highlights that the spinal cord vascular network is crucial to maintaining the efficacy of analgesics to provide pain relief.
| Item Type: | Journal article |
|---|---|
| Publication Title: | Frontiers in Pain Research |
| Creators: | Da Vitoria Lobo, M.E., Madden, R., Liddell, S., Hirashima, M. and Hulse, R.P. |
| Publisher: | Frontiers Media |
| Date: | 2023 |
| Volume: | 4 |
| ISSN: | 2673-561X |
| Identifiers: | Number Type 10.3389/fpain.2023.1190440 DOI 1771966 Other |
| Rights: | © 2023 Da Vitoria Lobo, Madden, Liddell, Hirashima and Hulse. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Linda Sullivan |
| Date Added: | 20 Jun 2023 08:07 |
| Last Modified: | 20 Jun 2023 08:07 |
| URI: | https://irep.ntu.ac.uk/id/eprint/49228 |
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