Impairment and restoration of the blood-nerve barrier and its correlation with pain following gradual nerve elongation of the rat sciatic nerve

Fujino, Keitaro; Yokota, Atsushi; Ohno, Katsunori; Hirofuji, Shinji; Neo, Masashi

doi:10.1080/00207454.2020.1738430

Cited by 3 publications

(3 citation statements)

References 25 publications

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“…Moreover, the level of the nerve damage (upper part or middle part of the brachium) and, therefore, the distance the regenerating nerve has to overcome, as well as the defect length, influences the functional recovery [ 60 , 61 ]. In any case, a tension free-coaptation is paramount to achieve optimal functional results, given the detrimental effects of tension on intraneural perfusion [ 62 , 63 , 64 , 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury

et al. 2022

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The rat median nerve model is a well-established and frequently used model for peripheral nerve injury and repair. The grasping test is the gold-standard to evaluate functional recovery in this model. However, no comprehensive review exists to summarize the course of functional recovery in regard to the lesion type. According to PRISMA-guidelines, research was performed, including the databases PubMed and Web of Science. Groups were: (1) crush injury, (2) transection with end-to-end or with (3) end-to-side coaptation and (4) isogenic or acellular allogenic grafting. Total and respective number, as well as rat strain, type of nerve defect, length of isogenic or acellular allogenic allografts, time at first signs of motor recovery (FSR) and maximal recovery grasping strength (MRGS), were evaluated. In total, 47 articles met the inclusion criteria. Group I showed earliest signs of motor recovery. Slow recovery was observable in group III and in graft length above 25 mm. Isografts recovered faster compared to other grafts. The onset and course of recovery is heavily dependent from the type of nerve injury. The grasping test should be used complementary in addition to other volitional and non-volitional tests. Repetitive examinations should be planned carefully to optimize assessment of valid and reliable data.

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Section: Discussionmentioning

confidence: 99%

The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury

et al. 2022

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“…However, the mechanisms are different between the PNS and CNS in regulating the immune cells (9). Blood-nerve barrier (BNB) disruption has been found to participate in many diseases including chronic pain (10)(11)(12). The neurovasculature of the BNB mainly comprises endothelial cells that are coupled to neurons via glial cells (13).…”

Section: Original Articlementioning

confidence: 99%

“…Peripheral nerve injuries increase the permeability of the BNB and induce neuropathic pain through the injured afferents ( 14 ). This chronic pain is maintained by continuous neuroinflammation ( 11 , 15 ). After PNS injury, the role of monocytes and macrophages are reported to remain peripheral.…”

Section: Introductionmentioning

confidence: 99%

The peripheral Epac1/p-Cav-1 pathway underlies the disruption of the vascular endothelial barrier following skin/muscle incision and retraction-induced chronic postsurgical pain

Chen¹,

Qing²,

Liu³

et al. 2022

Ann Transl Med

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Background: Vascular endothelial barrier disruption is pivotal in the development of acute and chronic pain. Here, we demonstrate a previously unidentified molecular mechanism in which activation of the peripheral Epac1/p-Cav-1 pathway accelerated the disruption of the vascular endothelial barrier, thereby promoting chronic postsurgical pain (CPSP). Methods:We established a rat model of CPSP induced by skin/muscle incision and retraction (SMIR).Pain behaviors were assessed by the mechanical withdrawal threshold (MWT) at different times. Local muscle tissues around the incision were isolated to detect the vascular permeability and the expression of Epac1 and Cav-1. They were assessed by western blot and immunofluorescence staining.Results: SMIR increased vascular endothelial permeability and the number of macrophages and endothelial cells in the muscle tissues around the incision. The peripheral upregulation of Epac1 was macrophagederived, whereas that of p-Cav-1 was both macrophage and endothelial cell-derived in the SMIR model. Moreover, the Epac1 agonist 8-pCPT could induce mechanical sensitivity, increase the expression of p-Cav-1, and disrupt vascular endothelial barrier in normal rats. The Epac1 inhibitor CE3F4 attenuated established SMIR-induced mechanical hyperalgesia, the upregulation of p-Cav-1 and vascular endothelial barrier.Finally, we showed that intrathecal injection of Cav-1siRNA relieved SMIR-induced mechanical allodynia, but had no effects of the expression of Epac1.Conclusions: Collectively, these results revealed a molecular mechanism for modulating CPSP through the peripheral Epac1/Cav-1 pathway. Importantly, targeting Epac1/Cav-1 signaling might be a potential treatment for CPSP.

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Blood-nerve barrier enhances chronic postsurgical pain via the HIF-1α/ aquaporin-1 signaling axis

Wu,

Yao,

Meng

et al. 2023

BMC Anesthesiol

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Background Blood nerve barrier (BNB) participates in the development of neuropathic pain. AQP1 is involved in peripheral pain perception and is negatively correlated with HIF-1α phenotype, which regulates endothelial permeability. However, the role of HIF-1α-AQP1-mediated BNB dysfunction in Chronic Postsurgical Pain (CPSP) has not been reported. Methods Male Sprague-Dawley rats were randomized into 5 groups: (i) Naive group; (ii) Sham group; (iii) SMIR group: skin/muscle incision and retraction for one hour. Behavioral tests were performed for the three groups, BNB vascular permeability and western blotting were conducted to determine HIF-1α and AQP1 protein expression. (iv) The SMIR + HIF-1α inhibitor group; (v) SMIR + DMSO group. Rats in the two groups were administered with HIF-1α inhibitor (2ME2) or DMSO intraperitoneally on the third day post-SMIR surgery followed by performance of behavioral tests, BNB permeability assessment, and determination of HIF-1α, AQP1 and NF200 protein levels. Results The permeability of BNB was significantly increased and the expression of AQP1 was downregulated on the 3rd and 7th days post-operation. AQP1 is mainly located in neurons and NF200, CGRP-positive nerve fibers. HIF-1α was highly expressed on the third day post-operation. HIF-1α inhibitor reversed the decrease in AQP1 expression and increase in NF200 expression, barrier permeability and hyperalgesia induced by SMIR on the 3rd day post-surgery. Conclusions Early dysfunction of BNB mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism to promote acute postoperative painful transformation of CPSP. Preadaptive protection of endothelial cells around nerve substructures may be an important countermeasure to inhibit CPSP transformation. Early impairment of BNB function mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism for promoting acute postoperative pain transformation of CPSP.

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Impairment and restoration of the blood-nerve barrier and its correlation with pain following gradual nerve elongation of the rat sciatic nerve

Cited by 3 publications

References 25 publications

The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury

The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury

The peripheral Epac1/p-Cav-1 pathway underlies the disruption of the vascular endothelial barrier following skin/muscle incision and retraction-induced chronic postsurgical pain

Blood-nerve barrier enhances chronic postsurgical pain via the HIF-1α/ aquaporin-1 signaling axis

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