Nociceptive, emotional, electrophysiological, and histological characterization of the chronic constriction injury model in female Wistar Han rats

Fonseca-Rodrigues, Diana; Laranjeira, Inês; Barbosa, João; Lamas, Nuno Jorge; Amorim, Diana; Almeida, Armando; Pinto-Ribeiro, Filipa

doi:10.1016/j.brainresbull.2020.11.018

Cited by 5 publications

(5 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 It was reported that NP affects 7− 10% of the population and among them females have a higher prevalence and severity than males. 2 In the patients with type 2 diabetes mellitus, the development of NP was not associated with the level of serum vitamin D, but was associated with female gender. 3 Epidemiologic studies reported that women suffer from more persistent pains and use analgesic medication more often than males.…”

Section: ■ Introductionmentioning

confidence: 97%

“…Neuropathic pain (NP), characterized by hyperalgesia and allodynia, is a type of chronic pain with complicated and heterogeneous pathogenesis . It was reported that NP affects 7–10% of the population and among them females have a higher prevalence and severity than males . In the patients with type 2 diabetes mellitus, the development of NP was not associated with the level of serum vitamin D, but was associated with female gender .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DUSP1 Promotes Microglial Polarization toward M2 Phenotype in the Medial Prefrontal Cortex of Neuropathic Pain Rats via Inhibition of MAPK Pathway

Wang

Jiang

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Shifting microglial polarization from M1 toward M2 phenotype represents a promising therapeutic strategy for neuropathic pain (NP). Dualspecificity phosphatase-1 (DUSP1) is a key component in regulating antiinflammatory response. The medial prefrontal cortex (mPFC) is implicated in emotional disorders associated with NP and constitutes a neuroanatomical substrate for exploring mechanisms underlying NP. This study aims to investigate whether DUSP1 regulates microglial M1/M2 polarization in the mPFC in a rat model of NP. Rat model of NP was established by chronic constriction injury (CCI) of the rat sciatic nerve. Lipopolysaccharide (LPS) was used to activate HAPI rat microglial cells as an in vitro inflammatory model. CCI-induced decreased pain threshold, increased cell apoptosis in mPFC, elevated proinflammatory M1/M2 microglia ratio, and activated MAPK signaling in the mPFC of rats. Importantly, intra-mPFC injection of DUSP1-expressing lentivirus counteracted these abnormalities. In vitro assay further confirmed that DUSP1 overexpression switched microglial M1 to M2 polarization through inhibition of MAPK signaling activation. DUSP1 switched microglial M1 to M2 polarization in the mPFC and attenuated CCI-induced NP by inhibiting the MAPK signaling.

show abstract

Section: ■ Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

DUSP1 Promotes Microglial Polarization toward M2 Phenotype in the Medial Prefrontal Cortex of Neuropathic Pain Rats via Inhibition of MAPK Pathway

Wang

Jiang

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Third, CCI female mice display different mechanical and thermal hyperalgesia from males. 39 This research did not consider the sexual dimorphism in CCI-induced NP. Therefore, female mice need to be conducted sex-specific differences in pain-induced reactivity in future studies.…”

Section: Discussionmentioning

confidence: 97%

Inhibition of Cyclophilin A-Metalloproteinase-9 Pathway Alleviates the Development of Neuropathic Pain by Promoting Repair of the Blood-Spinal Cord Barrier

Wang,

Yang

et al. 2023

Anesthesia &Amp; Analgesia

View full text Add to dashboard Cite

BACKGROUND: Dysfunction of the blood-spinal cord barrier (BSCB) contributes to the occurrence and development of neuropathic pain (NP). Previous studies revealed that the activation of cyclophilin A (CypA)-metalloproteinase-9 (MMP9) signaling pathway can disrupt the integrity of the blood-brain barrier (BBB) and aggravate neuroinflammatory responses. However, the roles of CypA-MMP9 signaling pathway on BSCB in NP have not been studied. This study aimed to investigate the effect of CypA on the structure and function of the BSCB and pain behaviors in mice with NP. METHODS: We first created the mouse chronic constriction injury (CCI) model, and they were then intraperitoneally injected with the CypA inhibitor cyclosporine A (CsA) or vehicle. Pain behaviors, the structure and function of the BSCB, the involvement of the CypA-MMP9 signaling pathway, microglia activation, and expression levels of proinflammatory factors in mice were examined. RESULTS: CCI mice presented mechanical allodynia and thermal hyperalgesia, impaired permeability of the BSCB, downregulated tight junction proteins, activated CypA-MMP9 signaling pathway, microglia activation, and upregulated proinflammatory factors, which were significantly alleviated by inhibition of CypA. CONCLUSIONS: Collectively, the CypA-MMP9 signaling pathway is responsible for CCI-induced NP in mice by impairing the structure and function of the BSCB, and activating microglia and inflammatory responses.

show abstract

“…Animals operated to develop chronic constriction injury (CCI) have been used as a model for the study of anxiety, depression, and mnemonic alterations as behaviors related to NP. 16 Similarly, the partial sciatic nerve ligation (pSNL) model is also used to assess the development of mood disorders associated with NP. 48 Consistent with these findings, a temporal analysis of the development of pain and pain-associated symptoms showed that SNI mice developed a persistent and prolonged mechanical allodynia and thermal hyperalgesia in the first days after injury, followed by the appearance of NP-associated anxiety and depression 14 days after surgery, which becomes increasingly stronger after 28 days.…”

Section: Discussionmentioning

confidence: 99%

“…1114 V. Borgonetti, N. Galeotti • 164 (2023)[1106][1107][1108][1109][1110][1111][1112][1113][1114][1115][1116][1117] …”

unclassified

Microglia senescence is related to neuropathic pain–associated comorbidities in the spared nerve injury model

Borgonetti

Galeotti

2022

Pain

View full text Add to dashboard Cite

The increased presence of senescent cells in different neurological diseases suggests the contribution of senescence in the pathophysiology of neurodegenerative disorders. Microglia can adapt to any type of disturbance of the homeostasis of the central nervous system, and its altered activity can lead to permanent and unresolvable damage. The aim of this work was to characterize the behavioural phenotype of spared nerve injury mice and then associate it with senescence-related mechanisms. In this work, we investigated the timing of the onset of anxiety, depression, or memory decline associated with peripheral neuropathic pain and their correlation with the presence of microglial cellular senescence. Spared nerve injury mice showed a persistent pain hypersensitivity from 3 days after surgery. Twenty-eight days after nerve injury, they also developed anxiety, depression, and cognitive impairment. The appearance of these symptoms was coincident to a significant increase of senescence markers, such as b-galactosidase and senescent-associated secretory phenotype, at the microglial level in the spinal cord and hippocampus of spared nerve injury animals. These markers were unaltered at previous time points. In murine immortalized microglial cells (BV2) stimulated with LPS 500 ng/mL for 10 days (4 hours/day) every other day, we observed an increase of b-galactosidase and senescent-associated secretory phenotype appearance, a reduction of cell viability, and an increase of senescence-associated heterochromatin foci. Therefore, present findings could represent an important step to a better understanding of the pathophysiological cellular mechanisms in comorbidities related to neuropathic pain states.

show abstract

Nociceptive, emotional, electrophysiological, and histological characterization of the chronic constriction injury model in female Wistar Han rats

Cited by 5 publications

References 59 publications

DUSP1 Promotes Microglial Polarization toward M2 Phenotype in the Medial Prefrontal Cortex of Neuropathic Pain Rats via Inhibition of MAPK Pathway

DUSP1 Promotes Microglial Polarization toward M2 Phenotype in the Medial Prefrontal Cortex of Neuropathic Pain Rats via Inhibition of MAPK Pathway

Inhibition of Cyclophilin A-Metalloproteinase-9 Pathway Alleviates the Development of Neuropathic Pain by Promoting Repair of the Blood-Spinal Cord Barrier

Microglia senescence is related to neuropathic pain–associated comorbidities in the spared nerve injury model

Contact Info

Product

Resources

About