Gene Expression Profiling of Contralateral Dorsal Root Ganglia Associated with Mirror-Image Pain in a Rat Model of Complex Regional Pain Syndrome Type-I

Nie, Huimin; Liu, Boyu; Yin, Chengyu; Chen, Ruixiang; Wang, Jie; Zeng, Danyi; Tai, Yan; Xie, Jingdun; He, Dongwei

doi:10.2147/jpr.s322372

Cited by 10 publications

(5 citation statements)

References 56 publications

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“…1 A, B). Although no swelling ever occurred, contralateral hindpaw developed obvious and persistent mechanical allodynia similarly to ipsilateral hindpaw, which was a typical sign of mirror-image pain (MIP) [ 39 ] (Additional file 1 : Fig. S1C, D&E).…”

Section: Resultsmentioning

confidence: 99%

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CXCL13 contributes to chronic pain of a mouse model of CRPS-I via CXCR5-mediated NF-κB activation and pro-inflammatory cytokine production in spinal cord dorsal horn

Wang

Yin

Pan

et al. 2023

J Neuroinflammation

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Background Complex regional pain syndrome type-I (CRPS-I) causes excruciating pain that affect patients’ life quality. However, the mechanisms underlying CRPS-I are incompletely understood, which hampers the development of target specific therapeutics. Methods The mouse chronic post-ischemic pain (CPIP) model was established to mimic CRPS-I. qPCR, Western blot, immunostaining, behavioral assay and pharmacological methods were used to study mechanisms underlying neuroinflammation and chronic pain in spinal cord dorsal horn (SCDH) of CPIP mice. Results CPIP mice developed robust and long-lasting mechanical allodynia in bilateral hindpaws. The expression of inflammatory chemokine CXCL13 and its receptor CXCR5 was significantly upregulated in ipsilateral SCDH of CPIP mice. Immunostaining revealed CXCL13 and CXCR5 was predominantly expressed in spinal neurons. Neutralization of spinal CXCL13 or genetic deletion of Cxcr5 (Cxcr5−/−) significantly reduced mechanical allodynia, as well as spinal glial cell overactivation and c-Fos activation in SCDH of CPIP mice. Mechanical pain causes affective disorder in CPIP mice, which was attenuated in Cxcr5−/− mice. Phosphorylated STAT3 co-expressed with CXCL13 in SCDH neurons and contributed to CXCL13 upregulation and mechanical allodynia in CPIP mice. CXCR5 coupled with NF-κB signaling in SCDH neurons to trigger pro-inflammatory cytokine gene Il6 upregulation, contributing to mechanical allodynia. Intrathecal CXCL13 injection produced mechanical allodynia via CXCR5-dependent NF-κB activation. Specific overexpression of CXCL13 in SCDH neurons is sufficient to induce persistent mechanical allodynia in naïve mice. Conclusions These results demonstrated a previously unidentified role of CXCL13/CXCR5 signaling in mediating spinal neuroinflammation and mechanical pain in an animal model of CRPS-I. Our work suggests that targeting CXCL13/CXCR5 pathway may lead to novel therapeutic approaches for CRPS-I.

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Section: Resultsmentioning

confidence: 99%

“…Currently, the mystery underlying MIP is far from being understood. Peripheral and spinal mechanisms are both proposed to contribute to MIP [ 39 , 64 ]. Blocking spinal glia activation and pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, significantly alleviate MIP of neuropathic pain model animals.…”

Section: Discussionmentioning

confidence: 99%

CXCL13 contributes to chronic pain of a mouse model of CRPS-I via CXCR5-mediated NF-κB activation and pro-inflammatory cytokine production in spinal cord dorsal horn

Wang

Yin

Pan

et al. 2023

J Neuroinflammation

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“…The number of TRPV1 positively stained DRG neurons were divided by the total number of DRG neurons identified by positive NeuN staining in order to calculate % of TRPV1 positive neurons. Three images were randomly selected from each tissue section, averaged, and then analyzed according to methods we previously described [ 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

Electroacupuncture improves gout arthritis pain via attenuating ROS-mediated NLRP3 inflammasome overactivation

et al. 2023

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Background Gout results from disturbed uric acid metabolism, which causes urate crystal deposition in joints and surrounding tissues. Gout pain management is largely limited to colchicine and nonsteroidal anti-inflammatory drugs. Constant usage of these medications leads to severe side effects. We previously showed electroacupuncture (EA) is effective for relieving pain in animal model of gout arthritis. Here we continued to study the mechanisms underlying how EA alleviates gout pain. Methods Monosodium urate was injected into ankle joint to establish gout arthritis model in mice. EA or sham EA was applied at ST36 and BL60 acupoints of model animals. Biochemical assays, immunostaining, live cell Ca2+ imaging and behavioral assays were applied. Results Model mice displayed obvious mechanical allodynia, accompanied with gait impairments. EA attenuated mechanical hypersensitivities and improved gait impairments. EA reduced the overexpression of NLRP3 inflammasome signaling molecules in ankle joints of model animals. EA-induced anti-allodynia, as well as inhibition on NLRP3 inflammasome, were mimicked by antagonizing but abolished by activating NLRP3 inflammasome via pharmacological methods. EA attenuated oxidative stress, an upstream signaling of NLRP3 inflammasome in ankle joints of model mice. Exogenously increasing oxidative stress abolished EA’s inhibitory effect on NLRP3 inflammasome and further reversed EA’s anti-allodynic effect. EA reduced neutrophil infiltrations in ankle joint synovium, a major mechanism contributing to oxidative stress in gout. Pharmacological blocking NLRP3 inflammasome or EA reduced TRPV1 channel overexpression in dorsal root ganglion (DRG) neurons. Ca2+ imaging confirmed that EA could reduce functional enhancement in TRPV1 channel in DRG neurons during gout. Conclusions Our results demonstrate that EA reduces gout pain possibly through suppressing ROS-mediated NLRP3 inflammasome activation in inflamed ankle joints and TRPV1 upregulation in sensory neurons, supporting EA as a treatment option for gout pain.

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“…The whole procedure was derived from our previous studies (Yin et al, 2019 ; Nie et al, 2021 ). Briefly, the L3–5 DRG segments ipsilateral to the side of the ankle sprain injury were harvested and used for generating libraries for RNA-Seq.…”

Section: Methodsmentioning

confidence: 99%

Characterization of pain-related behaviors and gene expression profiling of peripheral sensory ganglia in a mouse model of acute ankle sprain

Pan

Yang

et al. 2023

Front. Behav. Neurosci.

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IntroductionLateral ankle sprain (LAS) is a very common type of joint injury. It occurred with high incidence among general population and especially among individuals participating sports and outdoor activities. A certain proportion of individuals who once developed LAS may suffer persistent ankle pain that affects daily activities. However, the mechanisms underlying LAS-induced pain still remained largely unknown.MethodsWe established a LAS mouse model and systematically evaluated the pain-related behaviors in this mouse model. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. Immunostaining was used to study glial cell and neuron activation in ipsilateral spinal cord dorsal horn (SCDH) of LAS model mice. Ibuprofen was used to treat LAS model mice.ResultsThe LAS model mice developed obvious signs of mechanical and heat hypersensitivities as well as gait impairments in ipsilateral hind paws. Besides, LAS model mice developed signs of pain-related emotional disorder, including pain-induced aversion. By RNA-Seq, we were able to identify certain differentially expressed genes and signaling pathways that might contribute to pain mechanisms of LAS mouse model. In addition, LAS model mice showed increased c-Fos and p-ERK immunoreactivity as well as astrocyte and microglia overactivation in ipsilateral spinal cord dorsal horn, indicating central sensitization might occur. Finally, LAS model mice respond to ibuprofen, a drug clinically used to treat ankle sprain pain.ConclusionOur study found LAS model mice may be used as a preclinical animal model for screening novel targets or therapies for ankle sprain. Thus, the study may further help to understand molecular mechanisms contributing to ankle sprain-induced pain.

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Gene Expression Profiling of Contralateral Dorsal Root Ganglia Associated with Mirror-Image Pain in a Rat Model of Complex Regional Pain Syndrome Type-I

Cited by 10 publications

References 56 publications

CXCL13 contributes to chronic pain of a mouse model of CRPS-I via CXCR5-mediated NF-κB activation and pro-inflammatory cytokine production in spinal cord dorsal horn

CXCL13 contributes to chronic pain of a mouse model of CRPS-I via CXCR5-mediated NF-κB activation and pro-inflammatory cytokine production in spinal cord dorsal horn

Electroacupuncture improves gout arthritis pain via attenuating ROS-mediated NLRP3 inflammasome overactivation

Characterization of pain-related behaviors and gene expression profiling of peripheral sensory ganglia in a mouse model of acute ankle sprain

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