N-methyl-d-aspartate receptor subunit 2B on keratinocyte mediates peripheral and central sensitization in chronic post-ischemic pain in male rats

Xu, Xiao‐Jun; Xin, Tao; Huang, Ping; Feng, Li; Liu, Qing; Xu, Li; Xu, Jijun; Huang, Yuguang

doi:10.1016/j.bbi.2020.02.003

Cited by 28 publications

(22 citation statements)

References 63 publications

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“…The role of neuronal NMDAR in generation of peripheral neuroinflammation and central sensitization has been confirmed in several preclinical and clinical studies [134][135][136]. Moreover, the experimental studies confirmed the expression of functionally active NMDAR in keratinocytes in human normal and inflamed skin, where they play a role in epidermal homeostasis and nociception [95,137].…”

Section: Treatments Acting On N-methyl-d-aspartate Receptorsmentioning

confidence: 68%

“…The preclinical studies showed stimulation of keratinocytes alone to be sufficient to induce neuronal hyperexcitability and pain behaviour in animals [87,88]. According to preclinical data, keratinocytes express several receptors and ion channels, playing role in nociception, such as Nav (Nav 1.1,1.2, 1.5,1.6,1.7,1.8), TRP (TRPV1-4), neurokinin 1 receptor (NK1-receptor, NK1R), TLR, interleukin receptors, α1-AR, endothelin1 receptors (ET1), calcitonin receptor-like receptor (CRLR), CB receptors, OR, NOP (nociceptin-orphanin opioid peptide) receptors (NOP-R), VGCC, NMDAR, and GABAR to mention a few [89][90][91][92][93][94][95][96]. The role of keratinocyte receptors and their overexpression in nociception has been confirmed in clinical observations.…”

Section: 4 the Role Of Skin Cells In Peripheral Mechanisms Of Npmentioning

confidence: 99%

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Peripheral Mechanisms of Neuropathic Pain—The Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain

et al. 2021

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Neuropathic pain in humans arises as a consequence of injury or disease of somatosensory nervous system at peripheral or central level. Peripheral neuropathic pain is more common than central neuropathic pain, and is supposed to result from peripheral mechanisms, following nerve injury. The animal models of neuropathic pain show extensive functional and structural changes occurring in neuronal and non-neuronal cells in response to peripheral nerve injury. These pathological changes following damage lead to peripheral sensitization development, and subsequently to central sensitization initiation with spinal and supraspinal mechanism involved. The aim of this narrative review paper is to discuss the mechanisms engaged in peripheral neuropathic pain generation and maintenance, with special focus on the role of glial, immune, and epithelial cells in peripheral nociception. Based on the preclinical and clinical studies, interactions between neuronal and non-neuronal cells have been described, pointing out at the molecular/cellular underlying mechanisms of neuropathic pain, which might be potentially targeted by topical treatments in clinical practice. The modulation of the complex neuro-immuno-cutaneous interactions in the periphery represents a strategy for the development of new topical analgesics and their utilization in clinical settings.

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Section: Treatments Acting On N-methyl-d-aspartate Receptorsmentioning

confidence: 68%

Section: 4 the Role Of Skin Cells In Peripheral Mechanisms Of Npmentioning

confidence: 99%

Peripheral Mechanisms of Neuropathic Pain—The Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain

et al. 2021

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“…16 The rat CPIP models exhibit several 2750 key features that resemble CRPS-I, including early hind paw edema, vascular disturbance and blood flow dysfunction in the hind paw, persistent bilateral mechanical allodynia and heat hyperalgesia, increased sensitivity to capsaicin treatment, etc. 15,16,22,37 At present, the CPIP model has become a commonly used animal model for mechanistic studies of CRPS-I. We and others found that the CPIP model rats develop robust MIP symptoms in the unaffected hind paw, including mechanical and thermal hypersensitivities.…”

Section: Discussionmentioning

confidence: 90%

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

Liu

Yin

et al. 2021

JPR

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Background: Mirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, such as complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remains largely unknown. The purpose of this study is to perform an expression profiling to identify genes related to MIP in an animal model of CRPS-I. Methods: We established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining, and animal behavioral assays were used to screen potential genes in the contralateral dorsal root ganglia (DRG) that may be involved in MIP. Results: The CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs sham rats. The expression changes of several representative DEGs were further verified by qPCR. Bioinformatics analysis indicated that the immune system process, innate immune response, and cell adhesion were among the mostly enriched biological processes, which are important processes involved in pain sensitization, neuroinflammation, and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small-to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and the pain mechanism in MIP. Conclusion:We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for the studying of MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.

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“…The rat CPIP models exhibits several key features that resemble CRPS-I, including early hind paw edema, vascular disturbance and blood ow dysfunction in hind paw, persistent bilateral mechanical allodynia and heat hyperalgesia and increased sensitivity to capsaicin treatment, etc. [13,14,19,33] At present, the CPIP model has become a commonly used animal model for CRPS-I mechanistic studies. We and others found that the CPIP model rats develop robust MIP symptoms in the unaffected hind paw, including mechanical and thermal hypersensitivities [13][14][15].…”

Section: Discussionmentioning

confidence: 99%

Expression Profiling of Contralateral Dorsal Root Ganglia of a Rat Model of Complex Regional Pain Syndrome Type-i Uncovers Potential Mechanisms Involved in Mirror-image Painexpression Profiling of Contralateral Dorsal Root Ganglia of a Rat Model of Complex Regional Pain Syndrome Type-i Uncovers Potential Mechanisms Involved in Mirror-image Pain

Nie

Liu

Yin

et al. 2021

Preprint

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Background: Mirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, including complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remained largely unknown. The purpose of this study is to perform an expression profiling to identify genes related with MIP in an animal model of CRPS-I. Methods: We established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining and animal behavioral assays were used to screen potential genes in contralateral dorsal root ganglia (DRG) that may be involved in MIP. Results: The CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs. control rats. The expression changes of several representative DEGs were verified by qPCR. Bioinformatics analysis indicated that immune system process, innate immune response and cell adhesion were among the mostly enriched biological processes, which are all important processes involved in pain sensitization, neuroinflammation and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small- to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and pain mechanism in MIP. Conclusions: We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for investigating MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.

show abstract

N-methyl-d-aspartate receptor subunit 2B on keratinocyte mediates peripheral and central sensitization in chronic post-ischemic pain in male rats

Cited by 28 publications

References 63 publications

Peripheral Mechanisms of Neuropathic Pain—The Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain

Peripheral Mechanisms of Neuropathic Pain—The Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain

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

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