Electroacupuncture Alleviates Mechanical Allodynia of a Rat Model of CRPS-I and Modulates Gene Expression Profiles in Dorsal Root Ganglia

Wang, Jie; Zheng, Xiaoli; Liu, Boyu; Yin, Chengyu; Chen, Ruixiang; Li, Xiaojie; Li, Yuanyuan; Nie, Huimin; Zeng, Danyi; He, Xiaofen; Jiang, Yongliang; Fang, Jianqiao

doi:10.3389/fneur.2020.580997

Cited by 8 publications

(6 citation statements)

References 53 publications

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“…The edema of the hindpaw was measured by the digital caliper as previously reported [19]. The percent increase in paw thickness was used to indicate the paw edema.…”

Section: Paw Edema Measurementmentioning

confidence: 99%

Nrf2 Activation Mediates Antiallodynic Effect of Electroacupuncture on a Rat Model of Complex Regional Pain Syndrome Type-I through Reducing Local Oxidative Stress and Inflammation

Yin

et al. 2022

Oxidative Medicine and Cellular Longevity

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Complex regional pain syndrome type-I (CRPS-I) represents a type of neurovascular condition featured by severe pain in affected extremities. Few treatments have proven effective for CRPS-I. Electroacupuncture (EA) is an effective therapy for pain relief. We explored the mechanism through which EA ameliorates pain in a rat CRPS-I model. The chronic postischemic pain (CPIP) model was established using Sprague-Dawley rats to mimic CRPS-I. We found that oxidative stress-related biological process was among the predominant biological processes in affected hindpaw of CPIP rats. Oxidative stress occurred primarily in local hindpaw but not in the spinal cord or serum of model rats. Antioxidant N-acetyl cysteine (NAC) attenuated mechanical allodynia and spinal glia overactivation in CPIP model rats, whereas locally increasing oxidative stress is sufficient to induce chronic pain and spinal glia overactivation in naive rats. EA exerted remarkable antiallodynia on CPIP rats by reducing local oxidative stress via enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Pharmacological blocking Nrf2 abolished antioxidative and antiallodynic effects of EA. EA reduced spinal glia overactivation, attenuated the upregulation of inflammatory cytokines, reduced the enhanced TRPA1 channel activity in dorsal root ganglion neurons innervating the hindpaws, and improved blood flow dysfunction in hindpaws of CPIP rats, all of which were mimicked by NAC treatment. Thus, we identified local oxidative injury as an important contributor to pathogenesis of animal CRPS-I model. EA targets local oxidative injury by enhancing endogenous Nrf2-mediated antioxidative mechanism to relieve pain and inflammation. Our study indicates EA can be an alternative option for CRPS-I management.

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“…The edema of the hindpaw was measured by the digital caliper as previously reported [19]. The percent increase in paw thickness was used to indicate the paw edema.…”

Section: Paw Edema Measurementmentioning

confidence: 99%

Nrf2 Activation Mediates Antiallodynic Effect of Electroacupuncture on a Rat Model of Complex Regional Pain Syndrome Type-I through Reducing Local Oxidative Stress and Inflammation

Yin

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…To further explore the mechanisms underlying CRPS-I, our recent study performed transcriptome profiling of gene expression changes in ipsilateral DRG and spinal cord dorsal horn (SCDH) of CPIP model rats by means of RNA-Sequencing [ 31 , 51 , 52 ]. We identified Nlrp3 gene expression to be significantly upregulated in SCDH of the CPIP model rats.…”

Section: Nlrp3 Inflammasome In Chronic Painmentioning

confidence: 99%

The NLRP3 inflammasome: an emerging therapeutic target for chronic pain

Chen

Yin

Fang

et al. 2021

J Neuroinflammation

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Chronic pain affects the life quality of the suffering patients and posts heavy problems to the health care system. Conventional medications are usually insufficient for chronic pain management and oftentimes results in many adverse effects. The NLRP3 inflammasome controls the processing of proinflammatory cytokine interleukin 1β (IL-1β) and is implicated in a variety of disease conditions. Recently, growing number of evidence suggests that NLRP3 inflammasome is dysregulated under chronic pain condition and contributes to pathogenesis of chronic pain. This review provides an up-to-date summary of the recent findings of the involvement of NLRP3 inflammasome in chronic pain and discussed the expression and regulation of NLRP3 inflammasome-related signaling components in chronic pain conditions. This review also summarized the successful therapeutic approaches that target against NLRP3 inflammasome for chronic pain treatment.

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“…The swelling of the hind paw was measured with a digital caliper as reported previously (Wang et al, 2020 ). The percent increase in paw thickness was used to indicate the paw edema.…”

Section: Methodsmentioning

confidence: 99%

Electroacupuncture Ameliorates Mechanical Allodynia of a Rat Model of CRPS-I via Suppressing NLRP3 Inflammasome Activation in Spinal Cord Dorsal Horn Neurons

Zhang

Chen

et al. 2022

Front. Cell. Neurosci.

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Complex regional pain syndrome type-I (CRPS-I) is a chronic neurological disorder that results in severe pain and affects patients' life quality. Conventional therapies usually lack effectiveness. Electroacupuncture (EA) is an effective physical therapy for relieving CRPS-I pain. However, the mechanism underlying EA-induced analgesia on CRPS-I still remain unknown. Spinal NLRP3 inflammasome was recently identified to contribute to pain and neuroinflammation in a rat model of CRPS-I by our group. Here, we aimed to study whether EA could inhibit spinal NLRP3 inflammasome activation, thus resulting in pain relief and attenuation of spinal neuroinflammation in the rat model of CRPS-I. We established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I. CPIP rats developed remarkable mechanical allodynia that could be relieved by daily EA intervention. NLRP3 inflammasome was activated in spinal cord dorsal horn (SCDH) of CPIP rats, accompanied with over-production of pro-inflammatory cytokine IL-1β. Immunostaining revealed that the cellular distribution of NLRP3 was predominantly located in SCDH neurons. Pharmacological activation of NLRP3 inflammasome per se is sufficient to produce persistent mechanical allodynia in naïve animals, whereas blocking NLRP3 inflammasome attenuates mechanical allodynia of CPIP rats. EA exclusively reduced NLRP3 overexpression in SCDH neurons and attenuated spinal glial cell over-activation in CPIP rats. EA-induced anti-allodynia with attenuation of spinal glial cell over-activation were all mimicked by intrathecal blocking NLRP3 inflammasome and reversed by activating NLRP3 inflammasome, respectively, through pharmacological methods. Finally, spinal blocking IL-1β attenuated mechanical allodynia and spinal glial cell over-activation in CPIP rats, resembling the effects of EA. In all, these results demonstrate that spinal NLRP3 inflammasome activation contributes to mechanical allodynia of the rat model of CRPS-I and EA ameliorates mechanical allodynia through inhibiting NLRP3 inflammasome activation in SCDH neurons. Our study further supports EA can be used as an effective treatment for CRPS-I.

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Electroacupuncture Alleviates Mechanical Allodynia of a Rat Model of CRPS-I and Modulates Gene Expression Profiles in Dorsal Root Ganglia

Cited by 8 publications

References 53 publications

Nrf2 Activation Mediates Antiallodynic Effect of Electroacupuncture on a Rat Model of Complex Regional Pain Syndrome Type-I through Reducing Local Oxidative Stress and Inflammation

Nrf2 Activation Mediates Antiallodynic Effect of Electroacupuncture on a Rat Model of Complex Regional Pain Syndrome Type-I through Reducing Local Oxidative Stress and Inflammation

The NLRP3 inflammasome: an emerging therapeutic target for chronic pain

Electroacupuncture Ameliorates Mechanical Allodynia of a Rat Model of CRPS-I via Suppressing NLRP3 Inflammasome Activation in Spinal Cord Dorsal Horn Neurons

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