Table 1.
Summary of in vivo Studies.
| Authors | Type of Animal | Diabetic Neuropathy | Acupuncture Treatment ① Acupuncture Types ② Acupoints ③ Retention Time ④ Treatment Duration (Sessions) ⑤ Frequency ⑥ Intensity ⑦ Control to Acupuncture |
Findings | |
|---|---|---|---|---|---|
| Manni et al., 2011 [51] |
SD Rats Female |
Single STZ, 65 mg/kg, i.p., >16.65 mM |
① | EA | STZ decreased latency of response to heat stimuli one to four weeks after administration (p < 0.05 vs. naive). EA at ST36 significantly increased the heat latency time at 4 weeks (p < 0.05 vs. control). STZ increased NGF levels both in the skin and in the spinal cord. EA only lowered that of the spinal cord (p < 0.05 vs. control). STZ increased SP levels in the skin but decreased in the spinal cord. EA only lowered that of the skin (p < 0.05 vs. control). STZ increased TrkA and pTyr496-TrkA levels in the skin. EA significantly decreased both (p < 0.05 vs. control). STZ significantly increased TRPV1 levels in the skin and the spinal cord. EA increased the TRPV1 level in the skin (p < 0.05 vs. control), whereas it decreased in the spinal cord (p < 0.05 vs. control). STZ decreased GAD-67 protein content in the spinal cord and EA significantly restored it (p < 0.05 vs. control). |
| ② | ST36 | ||||
| ③ | 30 min | ||||
| ④ | 3 weeks (6) | ||||
| ⑤ | 2 Hz | ||||
| ⑥ | 1.0–1.5 mA | ||||
| ⑦ | STZ alone | ||||
| Shi et al., 2013 [35] |
SD Rats Female |
Single STZ, 65 mg/kg, i.p., >16.7 mM |
① | EA | Single STZ injection-induced mechanical allodynia from week 2 to 6 (p < 0.01 vs. naive). Single EA treatment at ST36 significantly increased the mechanical allodynia from 2 h to 4 h compared to control (p < 0.05). EA on BL43 showed no significant effect compared to sham. Multiple EA treatment significantly increased the PWTs starting from 30 min to D5 (p < 0.05 vs. control). Multiple EA on BL43 did not show significant differences. Multiple EA treatment suppresses p65 and CBS expression in L4-6 DRG (p < 0.05 vs. control). |
| ② | ST36, BL43 | ||||
| ③ | 30 min | ||||
| ④ | One week (7) | ||||
| ⑤ | 2/100 Hz | ||||
| ⑥ | 1 mA | ||||
| ⑦ | EA at ST36 without electrical stimulation | ||||
| Zhou et al., 2018 [37] |
SD Rats Male |
Single STZ, 35 mg/kg, i.p., ≥11.1 mM |
① | EA | Single STZ injection induced mechanical allodynia 7 weeks after its injection (p < 0.01 vs. naive). EA treatment for 7 consecutive days on week 7 significantly attenuated mechanical allodynia (p < 0.01 vs. control). EA failed to improve myelin disruption and dissolute axoplasm of sciatic nerve induced by STZ. EA suppressed STZ induced upregulation of blood membrane protein levels of P2X3 receptor and p-PKC expressions in L4-6 DRG (p < 0.01 vs. control) Intraperitoneal injection of αβ-meATP or PMA inhibited the anti-allodynic effect of EA. PMA injection reversed downregulation of the plasma membrane protein levels of P2X3 receptors in the DRG. |
| ② | ST36, BL60 | ||||
| ③ | 30 min | ||||
| ④ | One week (7) | ||||
| ⑤ | 2 Hz | ||||
| ⑥ | 1–2 mA | ||||
| ⑦ | STZ alone | ||||
| Pan et al., 2019 [45] |
SD Rats Male |
Single STZ, 50 mg/kg, i.p., ≥16.7 mM |
① | EA | EA significantly increased the decreased heat sensitivity on week 14 (vs. control). EA significantly increased downregulated MCV and SCV (vs. control). MCV of naive group; 50.67 ± 10.71 m/s to 50.86 ± 11.04 m/s, control group; 45.00 ± 9.44 m/s to 20.63 ± 10.27 m/s, EA group; 43.84 ± 9.14 m/s to 30.26 ± 8.96 m/s. SCV of naive group; 51.26 ± 8.93 m/s to 48.32 ± 12.01 m/s; control group; 46.28 ± 11.65 m/s to 21.43 ± 11.51 m/s, EA group; 45.13 ± 9.49 m/s to 29.54 ± 9.39 m/s. EA ameliorated loose with irregular membranous masses myelin sheaths and damaged myelinated nerve fibers induced by STZ injection. EA decreased the upregulated proportion of apoptotic cells (vs. control). EA lowered mean level of GPR78 and Caspase-12. GRP78 of naive group; 0.21 ± 0.05, control; 0.48 ± 0.18, EA group; 0.29 ± 0.07. Caspase-12 of naive group; 0.22 ± 0.07, control; 0.48 ± 0.28, EA group; 0.26 ± 0.04. |
| ② | BL13, BL20, BL23, LI4, LR3, ST36, SP6 | ||||
| ③ | 20 min | ||||
| ④ | 12 weeks (72) | ||||
| ⑤ | 3 Hz | ||||
| ⑥ | - | ||||
| ⑦ | STZ alone | ||||
| Tang et al., 2020 [60] |
SD Rats Male | Single STZ, 35 mg/kg, i.p., ≥11.1 mM |
① | Manual acupuncture | Acupuncture treatment increased STZ-induced lowered MWT and TWL at D14 (p < 0.001) and D7-D14 (p < 0.05 (D7) and p < 0.001 (D10, D14)), respectively. Acupuncture lowered the serum levels of CXCR3, IL-1β, IL-6 and TNF-α significantly increased after STZ injection (p < 0.001 vs. control) at D14. Acupuncture lowered the serum level of GSP, TG, TC, LDL-C, and elevated the level of HDL-C altered due to STZ injection (p < 0.001 vs. control) at D14. Acupuncture reduced the increased expression of spinal P2X4 and OX42 expression (p < 0.001 vs. control). |
| ② | BL13, BL20, V23 | ||||
| ③ | 20 min | ||||
| ④ | 2 weeks (14) | ||||
| ⑤ | - | ||||
| ⑥ | - | ||||
| ⑦ | STZ alone | ||||
Abbreviations: αβ-meATP: αβ-methylene ATP; CBS: Cystathionine β Synthase; CXCR3: G protein-coupled receptor 9; DRG: Dorsal Root Ganglion; EA: Electro-Acupuncture; GAD-67: Glutamic Acid Decarboxylase-67; GPR78: G-Protein Coupled Receptor 78; GSP: Glycosylated Serum Protein; HDL: High-Density Lipoprotein; IL-1β: Interleukin-1β; IL-6: Interleukin-6; LDL: Low-Density Lipoprotein; MCV: Motor Conduction Velocity; MWT: Mechanical Withdrawal Threshold; NGF: Nerve Growth Factor; P2X3: P2X purinoceptor 3; P2X4: P2X purinoceptor 4; PMA: Phorbol 12-Myristate 13-Acetate; p-PKC: p-Protein Kinase C; PWT: Paw Withdrawal Threshold; SCV: Sensory Conduction Velocity; SD: Sprague Dawley; SP: Substance P; STZ: Streptozotocin; TC: Total Cholesterol; TG: Triglyceride; TNF-α: Tumor Necrosis Factor-α; TrkA: tropomyosin receptor kinase A; TRPV1: Transient Receptor Potential Vanilloid 1; TWL: Thermal Withdrawal Latency.