| Evidence Sentence: |
Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons |
| 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: |
Ca2+ imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. |
| Evidence Sentence: |
Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA's effect. |
| 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. |
| Evidence Sentence: |
EA Reduced the Overexpression of TLR4, MyD88, and TRPV1 in DRGs of Paclitaxel-Treated Rats |
| Evidence Sentence: |
It is well established that TRPV1 channel expression is increased in DRGs upon paclitaxel treatment and plays a critical role in mediating paclitaxel-induced peripheral neuropathic pain. |
| Evidence Sentence: |
Our immunofluorescence study revealed that the percentage of TRPV1 immune positive (TRPV1+) DRG neurons among all DRG neurons (stained with NeuN) and TRPV1 immunofluorescent staining intensity were both significantly increased in the paclitaxel-treated group (Figure 2A-C). |
| Evidence Sentence: |
Repeated EA treatment significantly reduced the overexpression of TRPV1 induced by paclitaxel treatment (Figure 2A-C). |
| Evidence Sentence: |
In contrast, sham EA had no effect on TRPV1 overexpression (Figure 2A-C). |
| Evidence Sentence: |
We further examined the expression of TRPV1 in DRGs by Western blotting. |
| Evidence Sentence: |
Western blotting revealed that TRPV1 expression was significantly increased in the L4-6 DRGs of paclitaxel-treated rats (Figure 3A). |
| Evidence Sentence: |
Repeated EA treatment significantly reduced TRPV1 overexpression in L4-6 DRGs, whereas sham EA had no effect (Figure 3A). |
| Evidence Sentence: |
Evidence suggests that TLR4 promotes TRPV1 overexpression in DRG neurons during paclitaxel-induced peripheral neuropathy and inflammation. |
| Evidence Sentence: |
TRPV1 Channel Functional Activity is Enhanced in DRG Neurons of Paclitaxel-Treated Rats, and EA Eliminated the Enhancement of TRPV1 Activity by Paclitaxel |
| Evidence Sentence: |
Since TRPV1 channel expression is upregulated in DRG neurons by paclitaxel treatment, we then performed live cell Ca2+ imaging to monitor the functional activities of TRPV1 channel in acutely dissociated L4-6 DRG neurons from paclitaxel-treated rats. |
| Evidence Sentence: |
Capsaicin, the specific TRPV1 agonist, was used to probe TRPV1 channel activities. |
| Evidence Sentence: |
Therefore, Ca2+ imaging experiments indicated that the functional activity of the TRPV1 channel was significantly increased in DRG neurons from paclitaxel-treated rats whereas repeated EA treatment attenuated the upregulated TRPV1 channel functional activity in DRG neurons induced by paclitaxel. |
| Evidence Sentence: |
Pharmacological Blocking of TRPV1 Mimics EA's Therapeutic Effect in Reducing Pain Hypersensitivities of Paclitaxel-Treated Rats |
| Evidence Sentence: |
To further confirm that EA's analgesic effect on paclitaxel-treated rats was due to TRPV1 modulation, we tested the effect of TRPV1 agonist capsaicin on EA's analgesic effect. |
| Evidence Sentence: |
These results further support the notion that EA's analgesic effect on paclitaxel-induced pain hypersensitivities is mediated by TRPV1 modulation. |
| Evidence Sentence: |
Capsaicin, the specific TRPV1 agonist, was used to probe TRPV1 channel activities. |
| Evidence Sentence: |
To further confirm that EA's analgesic effect on paclitaxel-treated rats was due to TRPV1 modulation, we tested the effect of TRPV1 agonist capsaicin on EA's analgesic effect. |
| Evidence Sentence: |
We next examined the effects of AMG9810, the specific TRPV1 antagonist, on the pain hypersensitivities of paclitaxel-treated rats. |
