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1.
Brain Res Bull ; 191: 30-39, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36240908

RESUMO

Low back and radicular pain syndromes, usually caused by local inflammation and irritation to the nerve root and dorsal root ganglion (DRG), are common throughout medical practice, but sufficient pain relief is scarce. In this study, we employed a chronic compression of DRG (CCD)-induced radicular pain model in rats to explore whether lysine-specific demethylase 1 (LSD1), a histone demethylase and transcriptional co-repressor, is involved in the pathological process of radicular pain. We found that LSD1 was expressed in various-sized DRG neurons by immunohistochemistry. CCD induced the upregulation of LSD1 in compressed L4-L5 DRGs. Moreover, either LSD1 small interfering RNAs or LSD1 inhibitor attenuated CCD-induced pain hypersensitivities. LSD1 was also upregulated in the injured lumbar 4 (L4) DRG in a spinal nerve ligation (SNL)-induced neuropathic pain mouse model. Nevertheless, LSD1 was not altered in L3-L5 DRGs in complete Freund's adjuvant-induced inflammatory pain mouse model, paclitaxel- or streptozotocin-induced neuropathic pain models. Furthermore, knockdown of LSD1 in the injured L4 DRG reversed SNL-induced pain hypersensitivities in mice. Therefore, we speculate that nerve injury induced the upregulation of LSD1 in the injured DRGs, which contributes to neuropathic pain hypersensitivities; thus, LSD1 may serve as a potential target for the treatment of radicular pain and neuropathic pain.


Assuntos
Hipersensibilidade , Neuralgia , Ratos , Camundongos , Animais , Gânglios Espinais/patologia , Lisina , Ratos Sprague-Dawley , Neuralgia/patologia , Nervos Espinhais/lesões , Modelos Animais de Doenças , Hipersensibilidade/complicações , Hipersensibilidade/patologia , Células Receptoras Sensoriais , Hiperalgesia/patologia
2.
Neuroreport ; 32(7): 548-554, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33850082

RESUMO

Neuron-glial-related cell adhesion molecule (NrCAM) is a neuronal cell adhesion molecule that has been shown to be involved in several cellular processes in the peripheral nervous system, including neurite outgrowth. We recently reported that alternative splicing of Nrcam mRNA at exon 10 in the dorsal root ganglion (DRG) contributes to the peripheral mechanism of neuropathic pain. Specially, Nrcam antisense oligonucleotides (ASO) targeting Nrcam exon 10, attenuated neuropathic pain hypersensitivities in mice. Here, we investigated the effect of Nrcam ASO on neurite outgrowth of DRG neurons in vitro. By immunostaining DRG neurons with different DRG markers, Nrcam ASO significantly reduced neurite lengths in neurofilament 200-, calcitonin gene-related peptide and isolectin B4-positive neurons in primary DRG neuronal culture. Moreover, Nrcam ASO activates epidermal growth factor receptor, which may mediate the effect of Nrcam ASO on neurite outgrowth of cultured DRG neurons. These results provide evidence that Nrcam ASO suppresses neurite outgrowth in DRG neurons by regulating alternative splicing of Nrcam gene at exon 10 and activation of epidermal growth factor receptor signaling, indicating the differential roles of NrCAM variants/isoforms in neurite outgrowth.


Assuntos
Moléculas de Adesão Celular/metabolismo , Gânglios Espinais/metabolismo , Crescimento Neuronal/genética , Oligonucleotídeos Antissenso/farmacologia , Células Receptoras Sensoriais/metabolismo , Processamento Alternativo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Moléculas de Adesão Celular/genética , Gânglios Espinais/efeitos dos fármacos , Lectinas/metabolismo , Camundongos , Crescimento Neuronal/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos
3.
Neurochem Res ; 46(3): 504-512, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387191

RESUMO

Electro-acupuncture (EA) has been used for clinic analgesia for many years. However, its mechanisms are not fully understood. We recently reported that AXL, a tyrosine kinase receptor, contributes to the peripheral mechanism of neuropathic pain. We here aim to figure out the significance of EA on neuropathic pain mediated by AXL in dorsal root ganglion (DRG). Spinal nerve ligation (SNL) was used as a neuropathic pain model. EA was applied at ''Huantiao'' (GB-30) and ''Yanglingquan'' (GB-34) acupoints for 30 min daily from day 7 to day 10 after SNL. EA not only gradually attenuated SNL-induced mechanical allodynia, but also suppressed the expression of phosphorylated AXL (p-AXL) and AXL in injured DRGs of SNL rats examined by western blotting and immunofluorescence. Moreover, intrathecal injection of the subthreshold dose of AXL inhibitor TP0903, significantly prolonged the analgesic time of single EA treatment and enhanced the analgesic effect of repeated EA treatments, suggesting a synergic effect of EA and AXL inhibitor. These results indicate that AXL signaling underlies EA analgesia and combination of AXL inhibitor and EA might be a new strategy for clinic analgesia on neuropathic pain.


Assuntos
Analgésicos/uso terapêutico , Eletroacupuntura , Neuralgia/tratamento farmacológico , Neuralgia/terapia , Pirimidinas/uso terapêutico , Receptores Proteína Tirosina Quinases/metabolismo , Sulfonamidas/uso terapêutico , Animais , Gânglios Espinais/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/terapia , Ligadura , Masculino , Ratos Sprague-Dawley , Nervos Espinhais/cirurgia
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