Downregulation of long noncoding RNA DLEU1 attenuates hypersensitivity in chronic constriction injury-induced neuropathic pain in rats by targeting miR-133a-3p/SRPK1 axis.
BACKGROUND
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. Therefore, our study focused on the significant role of DLEU1 in neuropathic pain rat models.


METHODS
We 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.


RESULTS
Our 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.


CONCLUSION
DLEU1 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.
['Li|Zhen|Z|', 'Li|Aiyuan|A|', 'Yan|Liping|L|', 'Yang|Tian|T|', 'Xu|Wei|W|', 'Fan|Pengju|P|0000-0001-6593-8663']
D000818:Animals D015415:Biomarkers D016207:Cytokines D004195:Disease Models, Animal D005260:Female D005786:Gene Expression Regulation D055785:Gene Knockdown Techniques D018836:Inflammation Mediators D035683:MicroRNAs D009437:Neuralgia D017288:Pain Threshold D017346:Protein Serine-Threonine Kinases D034622:RNA Interference D062085:RNA, Long Noncoding D051381:Rats D013116:Spinal Cord
DLEU1 Neuropathic pain miR-133a-3p SRPK1