Evidence Details for Tlr4
PMID Title Journal Year Abstract
31775332 Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons. Int J Mol Sci. 2019 Nov 25;20(23):5917. doi: 10.3390/ijms20235917. 2019 Nov 25 Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca(2+) imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA's effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain."

Evidence Sentence: Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression.
Evidence Sentence: EA Reduced the Overexpression of TLR4, MyD88, and TRPV1 in DRGs of Paclitaxel-Treated Rats
Evidence Sentence: TLR4 and its downstream signaling molecule MyD88 are both increased in DRGs of paclitaxel-treated rats and are involved in paclitaxel-induced peripheral neuropathic pain.
Evidence Sentence: Evidence suggests that TLR4 promotes TRPV1 overexpression in DRG neurons during paclitaxel-induced peripheral neuropathy and inflammation.
Evidence Sentence: Then, we continued to examine the effects of EA on the expression of TLR4 and MyD88 in DRGs of paclitaxel-treated rats.
Evidence Sentence: Consistent with previous reports, we found that the expression of TLR4 and MyD88 were both significantly upregulated in L4-6 DRGs of paclitaxel-treated rats compared with vehicle-treated rats by Western blotting (Figure 3B,C).
Evidence Sentence: Moreover, EA significantly reduced the upregulation of TLR4 and MyD88 expression in DRGs of paclitaxel-treated rats, whereas sham EA had no such effect (Figure 3B,C).
Evidence Sentence: Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons
Evidence Sentence: These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation.