Mutually beneficial effects of intensive exercise and GABAergic neural progenitor cell transplants in reducing neuropathic pain and spinal pathology in rats with spinal cord injury

Dugan, Elizabeth; Jergová, Stanislava; Sagen, Jacqueline

doi:10.1016/j.expneurol.2020.113208

Cited by 50 publications

(57 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, 1–6 weeks of treadmill running [ 17 – 19 , 22 – 24 , 27 – 34 ] and 6–39 days of swim training [ 16 , 19 – 21 ] reduced mechanical and thermal indices of nociception in SNI models of neuropathic pain. Further, there is consistent evidence that 7–14 weeks of treadmill running reduced mechanical indices of nociception in SCI models of neuropathic pain [ 38 , 39 , 45 ]. While there is less literature in DPN, CIPN, and CRPS models, in general, 4–10 weeks of treadmill running [ 48 , 49 , 51 , 52 , 54 ], 4–10 weeks of swim training [ 47 , 50 , 53 ], and 23–28 days of wheel running [ 55 ] ameliorated abnormal nociception in these models.…”

Section: Preclinical Evidencementioning

confidence: 97%

Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research

Leitzelar

Koltyn

2021

Sports Med - Open

View full text Add to dashboard Cite

Neuropathic pain is a disease of the somatosensory system that is characterized by tingling, burning, and/or shooting pain. Medication is often the primary treatment, but it can be costly, thus there is an interest in understanding alternative low-cost treatments such as exercise. The following review includes an overview of the preclinical and clinical literature examining the influence of exercise on neuropathic pain. Preclinical studies support the hypothesis that exercise reduces hyperalgesia and allodynia in animal models of neuropathic pain. In human research, observational studies suggest that those who are more physically active have lower risk of developing neuropathic pain compared to those who are less active. Exercise studies suggest aerobic exercise training (e.g., 16 weeks); a combination of aerobic and resistance exercise training (e.g., 10–12 weeks); or high-intensity interval training (e.g., 15 weeks) reduces aspects of neuropathic pain such as worst pain over the past month, pain over the past 24 h, pain scores, or pain interference. However, not all measures of pain improve following exercise training (e.g., current pain, heat pain threshold). Potential mechanisms and future directions are also discussed to aid in the goal of understanding the role of exercise in the management of neuropathic pain. Future research using standardized methods to further understanding of the dose of exercise needed to manage neuropathic pain is warranted.

show abstract

Section: Preclinical Evidencementioning

confidence: 97%

Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research

Leitzelar

Koltyn

2021

Sports Med - Open

View full text Add to dashboard Cite

show abstract

“…Emerging evidence indicates that exercise therapy can promote recovery after SCI [32][33][34][35]. It is well known that normal exercise training cannot be carried out by rats after SCI.…”

Section: Discussionmentioning

confidence: 99%

Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury

Ying

Xie

et al. 2020

Fluids Barriers CNS

View full text Add to dashboard Cite

Background The permeability of the blood-spinal cord barrier (BSCB) is mainly determined by junction complexes between adjacent endothelial cells (ECs), including tight junctions (TJs) and adherens junctions (AJs), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinases (MMPs) leads to inflammation, neurotoxin production, and neuronal apoptosis. The failure of new blood vessels to effectively regenerate is also an important cause of delayed recovery after SCI. For the first time, we introduced water treadmill training (TT) to help SCI rats successfully exercise and measured the effects of TT in promoting recovery after SCI and the possible mechanisms involved. Methods Sprague-Dawley (200–250 g) rats were randomly divided into the following three groups: sham operated, SCI, and SCI + TT. Animals were sacrificed at 7 or 14 days post-surgery. The degree of neurological deficit, tissue morphology and BSCB permeability were assessed by the Basso-Beattie-Bresnahan (BBB) motor function scale and appropriate staining protocols, and apoptosis, protein expression and vascular EC ultrastructure were assessed by TUNEL staining, Western blotting, immunofluorescence and transmission electron microscopy (TEM). Results Our experiments showed that TT reduced permeability of the BSCB and decreased structural tissue damage. TT significantly improved functional recovery when compared with that in the SCI group; TJ and AJ proteins expression increased significantly after TT, and training reduced apoptosis induced by SCI. TT could promote angiogenesis, and MMP-2 and MMP-9 expression was significantly inhibited by TT. Conclusions The results of this study indicate that TT promotes functional recovery for the following reasons: TT (1) protects residual BSCB structure from further damage, (2) promotes vascular regeneration, and (3) inhibits MMP-2/9 expression to mitigate BSCB damage.

show abstract

“…Emerging evidence indicates that exercise therapy can promote recovery after SCI [30][31][32][33]. It is well known that normal exercise training cannot be carried out in rats after SCI.…”

Section: Discussionmentioning

confidence: 99%

Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury

Ying

Xie

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The permeability of blood-spinal cord barrier (BSCB) is mainly determined by the junction complex between adjacent endothelial cells, including tight junctions (TJ) and adhesion junctions (AJ), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinase (MMP) leads to inflammation, neurotoxin production, and apoptosis of neurons. The failure of effective regeneration of new blood vessels is also an important reason for delayed recovery after SCI. We introduced water treadmill training (TT) for the first time, which can help SCI rats successfully exercise and measured the effect of TT in promoting recovery after SCI and possible mechanisms involved.Methods: Sprague-Dawley (200–250g) rats were randomly divided into three groups: Sham operated, SCI, and SCI + TT. Animals were sacrificed 7 d or 14 d post-surgery. The degree of neurological deficit as assessed by the Basso-Beattie-Bresnahan motor rating scale, tissue water content, BSCB permeability, apoptosis, protein expression and ultrastructure of vascular endothelial cells were assessed, Western blot, immunofluorescence and transmission electron microscopy. Results: Our experiments showed that TT reduced the permeability of BSCB and decreased tissue structural damage. TT improved functional recovery significantly when compared with the SCI group; TJ and AJ proteins expression increased significantly after TT training and training reduced apoptosis induced by SCI. TT can promote angiogenesis and the expression of MMP-2 and MMP-9 was significantly inhibited by TT.Conclusions: In this study, the results indicate that TT promotes functional recovery for the following reasons: (1) TT protects residual BSCB structure from further damage; (2) it promotes vascular regeneration; and (3) it inhibits the expression of MMP-2/9 to mitigate BSCB damage.

show abstract

Mutually beneficial effects of intensive exercise and GABAergic neural progenitor cell transplants in reducing neuropathic pain and spinal pathology in rats with spinal cord injury

Cited by 50 publications

References 97 publications

Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research

Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research

Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury

Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury

Contact Info

Product

Resources

About