MiR-1906 attenuates neuropathic pain in rats by regulating the TLR4/mTOR/ Akt signaling pathway

Abstract

Background This study determined the role of miR-1906 in neuropathic pain and proliferation in neuronal cells using a chronic constriction injury (CCI)-induced neuropathic pain (NP) rat model. Methodology NP was induced by CCI. Animals were divided into a sham group, an NP group, and a miR-1906 mimic group, which received 500 nmol/kg of a miR-1906 mimic intrathecally for 10 consecutive days following surgery. The effect of miR-1906 agomir was determined by estimating the thermal and mechanical withdrawal latency; an enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proinflammatory mediators. Western blotting and reverse-transcription polymerase chain reaction (RT-PCR) were used to determine protein expression in the spinal tissues of the CCI-induced neuropathic pain rat model. Results Administration of miR-1906 agomir increased the mechanical and thermal withdrawal latency period and the levels of inflammatory mediators compared with the NP group. Western blotting showed that treatment with miR-1906 agomir attenuated the levels of Akt, mTOR, TLR-4, and PI3K proteins in the spinal tissues of the CCI-induced neuropathic pain model. TLR-4 and NF-κB gene expression was lower in the miR-1906 agomir group than in the NP group. Conclusion miR-1906 gene stimulation reduced neuropathic pain by enhancing Akt/nTOR/PI3K and TLR-4/NF-κB pathway regulation.

NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR

“…Furthermore, mTOR is known to influence and regulate pain generation. For example, microRNA-1906 attenuates neuropathic pain in rats by regulating the TLR4/mTOR/AKT signaling pathway [ 39 ]. Moreover, inhibition of mTOR alleviates neuropathic pain induced by the chemotherapeutic bortezomib [ 40 ], and mTOR has been identified as a potential target for chronic pain [ 41 ].…”

“…Understanding these nociceptive mechanisms is key to mitigating pain, which remains clinically challenging and is often complicated by inflammation. Pain signals are amplified by the induction of inflammatory factors, which inhibit the mTOR pathway [ 39 ]. The mTOR pathway is also modulated by formalin-induced hypersensitivity and neuronal hyper-excitability [ 28 ].…”

The miR-1906 mimic attenuates bone loss in osteoporosis by down-regulating the TLR4/MyD88/NF‐κB pathway

“…Several clinical and pre-clinical studies found that miRs alter the bone remodelling process by affecting bone resorption, osteoclastogenic activity and bone formation. Furthermore, a miR-1906 mimic was found to enhance neuronal cells and reduce neuropathic pain by regulating the TLR-4/NF-kB pathway [10]. It was also found to be involved in the management of cerebral stroke [11].…”