A Transcriptomic Analysis of Neuropathic Pain in Rat Dorsal Root Ganglia Following Peripheral Nerve Injury

Sun, Wuping; Kou, Dongquan; Yu, Ziming; Yang, Shaomin; Jiang, Changyu; Xiong, Dehua; Xiao, Lizu; Deng, Qi; Xie, Hengtao; Hao, Yue

doi:10.1007/s12017-019-08581-3

Cited by 40 publications

(41 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic neuropathic pain is characterized by rather well‐described symptoms of hyperalgesia (increased sensitivity to painful stimuli), allodynia (perception of innocuous stimuli as painful), altered sensation and spontaneous pain. Once peripheral nerve is damaged, a series of pathophysiologic events are induced including neuronal hyperexcitability, changes in perineuronal homeostasis, alternations in gene expression and a strong immune response (Sun et al., 2019). Meanwhile, subsequent events in central pain processing pathways consolidate and exaggerate the steady‐state pain condition (Kuner, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, the von Frey hairs were pressed vertically on the hind plantar surface for approximately 4–5 s; each filament was used ten times; and a 5‐min interval was left between the different forces. The minimal force that caused lifting or licking responses at least five times was considered as the paw withdrawal threshold (Hao et al., 2019; Sun et al., 2019).…”

Section: Methodsmentioning

confidence: 99%

“…Lifting for normal locomotion was excluded. Behavioural testing was carried out with the experimenters blinded to treatment conditions (Hao et al., 2019; Sun et al., 2019).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Baicalin prevents the up‐regulation of TRPV1 in dorsal root ganglion and attenuates chronic neuropathic pain

Wang

Ling

et al. 2020

Veterinary Medicine & Sci

View full text Add to dashboard Cite

Neuropathic pain is a major public health problem because it has a considerable impact on life quality of patients. Neuropathic pain caused by a lesion or disease of the somatosensory nervous system, which causes unpleasant and abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia) (Finnerup et al., 2016). Therefore, it is warranted to develop novel effective analgesics for neuropathic pain relief and treatment. Most of the transient receptor potential (TRP) ion channels are calcium-permeable, non-selective cation channels (Montell & Rubin, 1989). TRP channels are characterized by various activation mechanisms (Nilius, 2007). It has been reported that some of the

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Baicalin prevents the up‐regulation of TRPV1 in dorsal root ganglion and attenuates chronic neuropathic pain

Wang

Ling

et al. 2020

Veterinary Medicine & Sci

View full text Add to dashboard Cite

show abstract

“…Studies looking at injury-induced changes in gene expression in DRG suggest that there is a wide breadth of molecules that become up or downregulated. Some common molecules that appear upregulated after injury across several studies include ATF3 and NPY (Hammer et al, 2010;Hu et al, 2016;Wu et al, 2016;Sun et al, 2020) as well as inflammatory molecules like IL-6 (Gong et al, 2016;Chen et al, 2017) and other key genes in immune cell signaling pathways like CD74 (Sun et al, 2020) and CDK6 (Chen et al, 2017). Most of these studies do not look at uninjured DRG specifically but instead pool together uninjured and injured DRG from injured animals.…”

Section: Emerging Molecular Markers Of Uninjured Neuronsmentioning

confidence: 99%

Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

Tran

Crawford

2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful. Studies that interrogate uninjured neurons in search of cell-specific mechanisms have shown that nerve injury alters intact, uninjured neurons resulting in an activity that drives stimulus-evoked pain. This review of neuropathic pain mechanisms summarizes cell-type-specific pathology of uninjured sensory neurons and the sensory ganglia that house their cell bodies. Uninjured neurons have demonstrated a wide range of molecular and neurophysiologic changes, many of which are distinct from those detected in injured neurons. These intriguing findings include expression of pain-associated molecules, neurophysiological changes that underlie increased excitability, and evidence that intercellular signaling within sensory ganglia alters uninjured neurons. In addition to well-supported findings, this review also discusses potential mechanisms that remain poorly understood in the context of nerve injury. This review highlights key questions that will advance our understanding of the plasticity of sensory neuron subpopulations and clarify the role of uninjured neurons in developing anti-pain therapies.

show abstract

“…Studies that have used RNA-seq to look at DRG changes, have primarily examined peripheral nerve injury models[9,12,27,34] with few examining non-nerve injury models (e.g., diabetic neuropathy[2],…”

mentioning

confidence: 99%

Dynamics of global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain

Stephens

Zhou

Renfro

et al. 2021

Preprint

View full text Add to dashboard Cite

Efforts to understand genetic variability involved in an individual’s susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms. To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by Chronic Constriction Injury (CCI) of the sciatic nerve and intra-plantar injection of Complete Freund’s Adjuvant (CFA) in rats. Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models. Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG.SummaryShared transcriptomic and epigenetic changes in two animal models improves our understanding of how chromatin structural changes alter DRG gene expression under persistent pain conditions.

show abstract

A Transcriptomic Analysis of Neuropathic Pain in Rat Dorsal Root Ganglia Following Peripheral Nerve Injury

Cited by 40 publications

References 43 publications

Baicalin prevents the up‐regulation of TRPV1 in dorsal root ganglion and attenuates chronic neuropathic pain

Baicalin prevents the up‐regulation of TRPV1 in dorsal root ganglion and attenuates chronic neuropathic pain

Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

Dynamics of global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain

Contact Info

Product

Resources

About