| Evidence Sentence: |
Acupuncture points injection mitigates chronic pain through transient receptor potential V1 in mice |
| Evidence Sentence: |
Transient receptor potential V1 (TRPV1) channels and associated molecules were all increased in CIP in mice dorsal root ganglion (DRG), spinal cord (SC), thalamus, and somatosensory cortex (SSC). |
| Evidence Sentence: |
The aforementioned molecules were mitigated in AI and Trpv1 knockout mice. |
| Evidence Sentence: |
Furthermore, Iba1-positive cells (microglial marker) were also potentiated and shared a similar tendency with TRPV1. |
| Evidence Sentence: |
These findings suggest that AI can alleviate chronic pain by reducing TRPV1 overexpression in both neuronal and microglial cells. |
| Evidence Sentence: |
AI treatment suppresses TRPV1-dependent mechanical and thermal hyperalgesia |
| Evidence Sentence: |
Similar to AI group mice, Trpv1-/- mice (Figure 1A, green column, n=8 mice) also exhibited little mechanical hyperalgesia following CIP. |
| Evidence Sentence: |
Thermal hyperalgesia was also not detected in the TRPV1-/- group (Figure 1B, #P<0.05, green column). |
| Evidence Sentence: |
Effects of CIP and AI on the expression levels of TRPV1 and associated signaling molecules in mouse dorsal root ganglia and spinal cord |
| Evidence Sentence: |
To examine the involvement of TRPV1 channels and related signaling factors in hyperalgesia and AI-mediated analgesia, changes in expression were examined by western blotting of DRG and SC tissue samples isolated after successful induction of hyperalgesia by CIP after reversal by AI (as confirmed by von Fey and Hargreaves' tests). |
| Evidence Sentence: |
In the DRG (Figure 2), TRPV1 protein expression was significantly increased by CIP induction compared with sham-treated controls, and this augmentation was significantly reversed by AI. |
| Evidence Sentence: |
Increased expression levels were also attenuated following CIP in Trpv1-/- mice compared with wild-type (WT) mice (CIP group). |
| Evidence Sentence: |
In addition, DRG expression levels of the phospho-activated mitogen-activated protein kinases (MAPKs) pERK (Figure 2E), pJNK (Figure 2F), and pp38 (Figure 2G) were elevated in CIP model mice, and these effects were reversed by AI and lower in Trpv1-/- mice than WT mice following CIP induction. |
| Evidence Sentence: |
Expression levels of pAkt (Figure 2H) and pmTOR Figure 2I), two downstream effectors of pPI3K, and the transcription factors pCREB (Figure 2J) and NFkappaB (Figure 2K) were up-regulated during CIP, reversed by AI, and lower following CIP in Trpv1-/- mice than WT mice. |
| Evidence Sentence: |
Finally, the activated microglial markers Iba1 (Figure 2N), S100B (Figure 2O), and RAGE (Figure 2P) were also elevated by CIP, and these responses were reversed by AI and lower in CIP model Trpv1-/- mice than CIP model WT mice. |
| Evidence Sentence: |
Increased TRPV1 and associated protein levels following CIP induction, reversal by AI, and suppression by Trpv1 gene deletion in the thalamus and somatosensory cortex |
| Evidence Sentence: |
Samples of thalamus (Figure 4) and somatosensory cortex (Figure 5) were also examined by western blotting for changes in the expression levels of TRPV1 and downstream signaling molecules following CIP induction and AI. |
| Evidence Sentence: |
In accordance with findings in DRG and SC, there were significant increases in the expression levels of TRPV1 (Figures 4A, 5A), pPKA (Figures 4B, 5B), pPI3K (Figures 4C, 5C), pPKC (Figures 4D, 5D), pERK (Figures 4E, 5E), pJNK (Figures 4F, 5F), pp38 (Figures 4G, 5G), pAkt (Figures 4H, 5H), pmTOR (Figures 4I, 5I), pCREB (Figures 4J, 5J), pNFkappaB (Figures 4K, 5K), Nav1.7 (Figures 4L, 5L), Nav1.8 (Figures 4M, 5M), Iba1 (Figure 4N, 5N), S100B (Figure 4O, 5O), and RAGE (Figures 4P, 5P) following CIP induction. |
| Evidence Sentence: |
Also in accord with findings in the DRG, these changes were attenuated by AI and lower in CIP model Trpv1-/- mice than in WT mice. |
| Evidence Sentence: |
Immunofluorescence images of the DRG revealed changes in TRPV1 immunoexpression that paralleled those measured by western blotting, with elevation following CIP induction compared with sham control mice and markedly lower expression levels in AI and Trpv1-/- groups (Figure 6A). |
| Evidence Sentence: |
Immunofluorescence staining also confirmed elevated expression of the glial cell marker Iba1 in the DRG following CIP induction, which was attenuated by AI treatment and Trpv1 gene deletion (Figure 6B). |
| Evidence Sentence: |
Further, TRPV1 and Iba1 were colocalized in CIP model mice, indicating that the elevation in tissue TRPV1 was mediated by increased expression in DRG glial cells. |
| Evidence Sentence: |
Consistent with western blotting results, this increase was reversed in AI and Trpv1-/- mice (Figure 6C). |
| Evidence Sentence: |
Similar changes in TRPV1 and Iba1 expression were also observed in the somatosensory cortex (Figure 7). |
| Evidence Sentence: |
Co-expression of TRPV1 and Iba1 in cells of the thalamusand somatosensory cortex |
| Evidence Sentence: |
Finally, we examined these changes in cellular TRPV1 and Iba1 in the thalamus (Figure 8) and somatosensory cortex (Figure 9). |
| Evidence Sentence: |
In accord with western blotting and other immunofluorescence results, TRPV1 immunoreactivity (Figure 8A) and Iba1 immunoreactivity (Figure 8B) were elevated concomitantly by CIP induction. |
| Evidence Sentence: |
Further, these elevated expression levels were reversed by AI (Figures 8A and 8B, respectively), while Iba1 expression was lower in CIP model Trpv1-/- mice than WT mice (Figure 8C). |
| Evidence Sentence: |
In the somatosensory cortex as well, TRPV1, Iba1, and TRPV1/Iba1 co-staining signals were all increased in CIP model mice and reversed by AI (Figure 9). |
| Evidence Sentence: |
Further, the changes in Iba1 were suppressed in Trpv1-/- mice. |
