Characterization of traumatic spinal cord injury model in relation to neuropathic pain in the rat

Batista, Chary Marquez; Mariano, Eric Domingos; Onuchic, Fernando; Dale, Camila Squarzoni; Santos, Gustavo Bispo dos; Cristante, Alexandre Fogaça; Otoch, José Pinhata; Teixeira, Manoel Jacobsen; Morgalla, Matthias; Lepski, Guilherme

doi:10.1080/08990220.2018.1563537

Cited by 8 publications

(4 citation statements)

References 76 publications

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“…It is worth mentioning also that our findings indicated that the ventrolateral funiculus was preserved on both sides of spinal cord. Traumatic spinal cord injuries lead to histological heterogeneity of the spinal cord parenchyma injury associated with variable pain responses, but when the ventrolateral funiculus is preserved after spinal cord injury, neuropathic pain may develop 35 – 37 . Considering that after mild SCI the ventrolateral funiculus was preserved in all groups, it can be suggested that antinociceptive effects observed would be associated with the GSE and CE treatments and not because of the severity of the injury effecting this region that it is necessary to preserve nociception responses.…”

Section: Discussionmentioning

confidence: 99%

Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

Bagó-Mas

Korimová

Deulofeu

et al. 2022

Sci Rep

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More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive effects, the present work aimed to study preventive effects on SCI-induced CNP development by repeated administration of two vegetal polyphenolic extracts: grape stalk extract (GSE) and coffee extract (CE). Thermal hyperalgesia and mechanical allodynia were evaluated at 7, 14 and 21 days postinjury. Then, gliosis, ERK phosphorylation and the expression of CCL2 and CX3CL1 chemokines and their receptors, CCR2 and CX3CR1, were analyzed in the spinal cord. Gliosis and CX3CL1/CX3CR1 expression were also analyzed in the anterior cingulate cortex (ACC) and periaqueductal gray matter (PAG) since they are supraspinal structures involved in pain perception and modulation. GSE and CE treatments modulated pain behaviors accompanied by reduced gliosis in the spinal cord and both treatments modulated neuron-glia crosstalk-related biomolecules expression. Moreover, both extracts attenuated astrogliosis in the ACC and PAG as well as microgliosis in the ACC with an increased M2 subpopulation of microglial cells in the PAG. Finally, GSE and CE prevented CX3CL1/CX3CR1 upregulation in the PAG, and modulated their expression in ACC. These findings suggest that repeated administrations of either GSE or CE after SCI may be suitable pharmacologic strategies to attenuate SCI-induced CNP development by means of spinal and supraspinal neuroinflammation modulation.

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Section: Discussionmentioning

confidence: 99%

Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

Bagó-Mas

Korimová

Deulofeu

et al. 2022

Sci Rep

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“…One of the most common and distressing symptoms suffered by patients with SCI is chronic neuropathic pain (61). Neuropathic pain can occur weeks, months, or years after the trauma, being one of the most significant complications where conventional treatments are mostly ineffective (62).…”

Section: Discussionmentioning

confidence: 99%

Cytokine expressions of spinal cord injury treated by neurotropin and nafamostat mesylate

Sun

Duan

et al. 2021

Ann Transl Med

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Background: Spinal cord injury (SCI) leads to severe physical disability and sensory dysfunction. Neurotropin (NTP) has been used clinically to alleviate neuropathic pain, while nafamostat mesylate (NM) used clinical on pancreatitis patients through inhibiting synthetic serine protease. Our previous studies showed that NTP and NM were able to repair SCI. However, the underlying mechanism has not been fully explored after treatment with these 2 different drugs. Methods:The drugs NTP and NM were administered on a contusion SCI Wistar rat model. Cytokine array analysis was performed to describe the changes of 67 proteins after acute SCI. Hierarchical clustering and volcano plot analysis were conducted to clarify protein change profiles. The differently expressed proteins related to biological processes were analyzed by functional protein association networks, Gene Ontology and pathway analysis. Flow cytometric analysis was detected to reflect the activation of immune system after drug intervention, while withdrawal threshold and BBB score were detected to evaluated the mechanical allodynia and functional recovery after SCI.Results: HGF, β-NGF, and activin were the 3 most upregulated proteins, while the receptor for RAGE, IL-1α, and TNF-α were the 3 most downregulated proteins after NTP treatment. Adiponectin, decorin and CTACK were the 3 most upregulated proteins, while RAGE, IL-1α, and IL-1β were the 3 most downregulated proteins in the NM group. Number of lymphocytes was decreased while BBB score was increased both in NTP and NM group. But only NTP could improve mechanical pain threshold after SCI. Conclusions:The PI3K-Akt, Jak-STAT signaling pathway and apoptosis might participate in SCI restoration by NTP, while the MAPK and NOD-like receptor signaling pathway may participated in repairing SCI with NM. We concluded that NTP regulated the microenvironment via a neuroprotective effect and inhibition of inflammation to repair SCI, while NM healed SCI through an anti-inflammatory effect. Both NTP and NM could down-regulate the activation of immune system and improve the functional recovery while only NTP could improve the pathological neuralgia after SCI. Elucidating the molecular mechanisms of these 2 clinical drugs indicates that they their expected to be effective clinical treatment for SCI.

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“…Spinal cord injury mice develop chronic hypersensitivity dependent on injury severity, with more severe contusion of the spinal cord resulting in an earlier and more severe reduction in mechanical and thermal thresholds. 10,37 Although these studies investigated how increasing the force of impact altered the pathology of SCI, we identified similar trends in hypersensitivity, locomotor ability, demyelination, and neuroinflammation as compression time is increased. Similar effects have been observed in the development of chronic pain in humans.…”

Section: Discussionmentioning

confidence: 86%

Spinal cord injury in mice affects central and peripheral pathology in a severity-dependent manner

Bannerman

Douchant

Segal

et al. 2021

Pain

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Chronic pain is a common medical complication experienced by those living with spinal cord injury (SCI) and leads to worsened quality of life. The pathophysiology of SCI pain is poorly understood, hampering the development of safe and efficacious therapeutics. We therefore sought to develop a clinically relevant model of SCI with a strong pain phenotype and characterize the central and peripheral pathology after injury. A contusion (50 kdyn) injury, with and without sustained compression (60 seconds) of the spinal cord, was performed on female C57BL/6J mice. Mice with compression of the spinal cord exhibited significantly greater heat and mechanical hypersensitivity starting at 7 days postinjury, concomitant with reduced locomotor function, compared with those without compression. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation in mice with compression compared with those without. As measured by flow cytometry, immune cell infiltration and activation were significantly greater in the spinal cord (phagocytic myeloid cells and microglia) and dorsal root ganglia (Ly6C 1 monocytes) after compression injury. We also decided to investigate the gastrointestinal microbiome, as it has been shown to be altered in patients with SCI and has recently been shown to play a role in immune system maturation and pain. We found increased dysbiosis of the gastrointestinal microbiome in an injury severity-dependent manner. The use of this contusioncompression model of SCI may help advance the preclinical assessment of acute and chronic SCI pain and lead to a better understanding of mechanisms contributing to this pain.

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Characterization of traumatic spinal cord injury model in relation to neuropathic pain in the rat

Cited by 8 publications

References 76 publications

Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

Cytokine expressions of spinal cord injury treated by neurotropin and nafamostat mesylate

Spinal cord injury in mice affects central and peripheral pathology in a severity-dependent manner

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