MiR‐101 promotes pain hypersensitivity in rats with chronic constriction injury via the MKP‐1 mediated MAPK pathway

Abstract

This study was performed to characterize the effect of microRNA‐101 (miR‐101) on the pain hypersensitivity in CCI rat models with the involvement of mitogen‐activated protein kinase phosphatase 1 (MKP‐1) in spinal cord microglial cells. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the developed CCI models were determined to assess the hypersensitivity of rats to mechanical stimulation and thermal pain. To assess inflammation, the levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α) in the spinal dorsal horns of CCI rats and lipopolysaccharide (LPS)‐activated microglial cells were examined. miR‐101 and MKP‐1 gain‐ and loss‐of‐function experiments were conducted in in vivo and in vitro settings to examine the roles of miR‐101 and MKP‐1 in CCI hypersensitivity and inflammation. The results showed that miR‐101 was highly expressed in the spinal dorsal horn and microglial cells of CCI rat models. Furthermore, overexpression of miR‐101 promoted the pain hypersensitivity in CCI rat models by reducing MWT and TWL. The overexpression of miR‐101 also promoted inflammation in LPS‐exposed microglial cells, as indicated by increased levels of IL‐1β, IL‐6 and TNF‐α. MiR‐101 was shown to target MKP‐1, inhibiting its expression. Moreover, miR‐101 promoted pain hypersensitivity in CCI rat models by inhibiting MKP‐1 expression and activating the mitogen‐activated protein kinase (MAPK) signalling pathway. Taken together, miR‐101 could potentially promote hypersensitivity and inflammatory response of microglial cells and aggravate neuropathic pain in CCI rat models by inhibiting MKP‐1 in the MAPK signalling pathway.

Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β

“…Gene array analysis of perturbations in primary afferent neurons following nerve injury have identified marked changes in genes coding for neuropeptides, cytokines, chemokines, receptors, ion channels, signal transduction molecules and synaptic vesicle proteins ( 146 , 233 ) as well as changes in expression of long non-coding RNA's ( 234 ) and microRNA's ( 235 – 238 ). The latter post-transcriptionally regulate the protein expression of hundreds of genes in a sequence-specific manner ( 239 ). For example the microRNA (miRNA-let-7b) can be released from DRG neurons by neuronal activation.…”

Electroacupuncture Suppresses CCI-Induced Neuropathic Pain through GABAA Receptors

“…Recently, emerging evidence has suggested that the spinal cord microglia is important regulator of neuropathic pain [3]. In response to neuropathic pain, the immune reaction is activated, with an initial activation of microglia in the spinal cord dorsal horn, ipsilateral to the injury [4].…”

Advanced insight into the O/W emulsions stabilising capacity of water‐soluble protein from Tenebrio molitor

“…When a spherical protein was adsorbed, the hydrophobic groups of the protein attached to the surface of the oil phase to form a physical barrier that wraps around the droplet to form a stable emulsion (Amine et al ., 2014). The spherical structure of TMP was conducive to the formation of stable viscoelastic film at the oil–water interfaces; in practice, this was an important factor for the application of TMP in emulsions to help maintain eminent stability (Qiu et al ., 2020).…”