Abstract
BackgroundNeuropathic pain belongs to chronic pain and is caused by the primary dysfunction of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) have been reported to regulate neuronal functions and play significant roles in neuropathic pain. DLEU1 has been indicated to have close relationship with neuropathic pain. Therefore, our study focused on the significant role of DLEU1 in neuropathic pain rat models.MethodsWe first constructed a chronic constrictive injury (CCI) rat model. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate hypersensitivity in neuropathic pain. RT-qPCR was performed to analyze the expression of target genes. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the concentrations of interleukin‐6 (IL-6), tumor necrosis factor‐α (TNF-α) and IL-1β. The underlying mechanisms of DLEU1 were investigated using western blot and luciferase reporter assays.ResultsOur findings showed that DLEU1 was upregulated in CCI rats. DLEU1 knockdown reduced the concentrations of IL‐6, IL‐1β and TNF‐α in CCI rats, suggesting that neuroinflammation was inhibited by DLEU1 knockdown. Besides, knockdown of DLEU1 inhibited neuropathic pain behaviors. Moreover, it was confirmed that DLEU1 bound with miR-133a-3p and negatively regulated its expression. SRPK1 was the downstream target of miR-133a-3p. DLEU1 competitively bound with miR-133a-3p to upregulate SRPK1. Finally, rescue assays revealed that SRPK1 overexpression rescued the suppressive effects of silenced DLEU1 on hypersensitivity in neuropathic pain and inflammation of spinal cord in CCI rats.ConclusionDLEU1 regulated inflammation of the spinal cord and mediated hypersensitivity in neuropathic pain in CCI rats by binding with miR-133a-3p to upregulate SRPK1 expression.
Highlights
Neuropathic pain, a chronic pain caused by nerve lesions or dysfunction, has become the most challenging neurological disease around the world
deleted in lymphocytic leukemia 1 (DLEU1) was upregulated in constriction injury (CCI) rats First, DLEU1 expression in the spinal cord tissues of rats was detected by RT-qPCR
DLEU1 knockdown suppressed inflammation in spinal cord tissues and attenuated neuropathic pain‐like behaviors Since IL-6, tumor necrosis factor‐α (TNF-α) and IL-1β are inflammation-associated cytokines and exert important function in neuropathic pain, the concentrations of inflammatory cytokines including IL-6, tumor necrosis factor (TNF)-α and IL-1β were detected in spinal cord tissues of CCI rats after DLEU1 was knocked down
Summary
Neuropathic pain, a chronic pain caused by nerve lesions or dysfunction, has become the most challenging neurological disease around the world. Neuropathic pain is related to hyperalgesia and dysphonia. Neuropathic pain affects many people in the world. Li et al Mol Med (2020) 26:104 the molecular regulatory mechanisms in neuropathic pain remain unknown. It is urgent to discover the specific molecular mechanisms and investigate effective therapeutic treatment for neuropathic pain. Neuropathic pain belongs to chronic pain and is caused by the primary dysfunction of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) have been reported to regulate neuronal functions and play significant roles in neuropathic pain. DLEU1 has been indicated to have close relationship with neuropathic pain. Our study focused on the significant role of DLEU1 in neuropathic pain rat models
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