The consequence of endothelial remodelling on the blood spinal cord barrier and nociception

Younis, Awais; Hardowar, Lydia; Barker, Sarah; Hulse, Richard P.

doi:10.1016/j.crphys.2022.03.005

Cited by 9 publications

(2 citation statements)

References 115 publications

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“…Vascular disturbances have proven to be fundamental in modulating nociceptive processing and underlie the development of chronic pain states(Younis et al ., 2022). However, investigations into the control of vascular function, in particular vascular tone have not been extensively explored in the context of nociception and onset of chronic pain states.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II type 1 receptor activation facilitates pain hypersensitivity via dorsal horn pericyte mediated vasoconstriction

Hardowar,

Sheavyn,

McTernan

et al. 2023

Preprint

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Vascular disturbance is a key factor in the development of neurological disease, with reduced integrity of the capillary network in the dorsal horn implicated in activation of nociceptive neural circuits and induction of pain hypersensitivity. Pericytes regulate capillary health and tone, with pericyte dysfunction in cerebral tissue associated with neurodegenerative disorders. Our work demonstrates that nociceptive processing is influenced by angiotensin II type 1 (AT1) receptor mediated pericyte contractility in the dorsal horn. Intravital imaging of the mouse spinal cord demonstrated angiotensin II induced cessation of spinal cord capillary perfusion. Intrathecal administration of angiotensin II induced pericyte contractility and narrowing of capillary diameter, which was accompanied by mechanical allodynia and heat hyperalgesia. Angiotensin II mediated pericyte activation and reduction of spinal cord blood flow, was prevented by inhibition of AT1 receptor via losartan treatment. In addition, losartan either systemically or intrathecally administered, prevented angiotensin II induced pain in male and female adult mice. This was associated with protection of the dorsal horn capillary endothelium, with intrathecal co-treatment with losartan preventing loss of CD31 immunoreactivity in the dorsal horn following administration of angiotensin II. This investigation demonstrates that AT1 mediated pericyte regulation of the dorsal horn capillary network, is fundamental in modulating nociceptive processing and perception of pain. Here we identify a novel cellular and mechanistic target for the development of new analgesic.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II type 1 receptor activation facilitates pain hypersensitivity via dorsal horn pericyte mediated vasoconstriction

Hardowar,

Sheavyn,

McTernan

et al. 2023

Preprint

Self Cite

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“…Astrocytes' close interplay with the endothelial cells ensures the barrier qualities by sustaining the existence of pumps and specialized ion channels, structures The BSCB comprises cellular and non-cellular components, with endothelial cells being one of the principal cells sustaining BSCB's impermeability. This endothelial tissue has unique characteristics, limiting the trans-flow of potential neurotoxic substances from the bloodstream to the spinal cord and serving as the principal molecular border at the spinal cord level [16]. To ensure high selectivity, the endothelial cells have a small number of endocytic processes and are closely sealed by tight junctions (TJs) [17], special intercellular protein bridges that will be discussed in detail below.…”

Section: The Blood-spinal Cord Barrier In Physiologic and Traumatic C...mentioning

confidence: 99%

Spinal Cord Injury Management Based on Microglia-Targeting Therapies

Schreiner,

Ciobanu

2024

JCM

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Spinal cord injury is a complicated medical condition both from the clinician’s point of view in terms of management and from the patient’s perspective in terms of unsatisfactory recovery. Depending on the severity, this disorder can be devastating despite the rapid and appropriate use of modern imaging techniques and convenient surgical spinal cord decompression and stabilization. In this context, there is a mandatory need for novel adjunctive therapeutic approaches to classical treatments to improve rehabilitation chances and clinical outcomes. This review offers a new and original perspective on therapies targeting the microglia, one of the most relevant immune cells implicated in spinal cord disorders. The first part of the manuscript reviews the anatomical and pathophysiological importance of the blood-spinal cord barrier components, including the role of microglia in post-acute neuroinflammation. Subsequently, the authors present the emerging therapies based on microglia modulation, such as cytokines modulators, stem cell, microRNA, and nanoparticle-based treatments that could positively impact spinal cord injury management. Finally, future perspectives and challenges are also highlighted based on the ongoing clinical trials related to medications targeting microglia.

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Role of the blood-spinal cord barrier: An adheren junction regulation mechanism that promotes chronic postsurgical pain

Zhao

Yao

Meng

et al. 2023

Biochemical and Biophysical Research Communications

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The consequence of endothelial remodelling on the blood spinal cord barrier and nociception

Cited by 9 publications

References 115 publications

Angiotensin II type 1 receptor activation facilitates pain hypersensitivity via dorsal horn pericyte mediated vasoconstriction

Angiotensin II type 1 receptor activation facilitates pain hypersensitivity via dorsal horn pericyte mediated vasoconstriction

Spinal Cord Injury Management Based on Microglia-Targeting Therapies

Role of the blood-spinal cord barrier: An adheren junction regulation mechanism that promotes chronic postsurgical pain

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