Acupuncture for chronic sciatica: protocol for a multicenter randomised controlled trial.

BACKGROUND: Chronic Sciatica is a disabling condition causing considerable medical, social and financial implications. Currently, there is no recognised long-term effective treatment to alleviate sciatica. Acupuncture has been widely used for treating chronic pains with persistent analgesic effects. We aim to evaluate the efficacy and safety of acupuncture for chronic sciatica with follow-up in 52 weeks. METHODS AND ANALYSIS: This is a multicenter randomised sham-controlled trial. A total of 216 patients with chronic sciatica will be enrolled and randomly assigned to the acupuncture or sham acupuncture group. There will be 10 treatment sessions applied in 4 weeks with frequency decreased over time. Patients will complete follow-ups during 52 weeks. The primary outcomes are changes in leg pain intensity and disability from baseline to week 4. Secondary outcomes include back pain intensity, frequency and bothersomeness, quality of life, and global perceived effect. Adverse events will be recorded in detail. ETHICS AND DISSEMINATION: Ethical approval of this trial was granted from the ethics committee of Beijing University of Chinese Medicine and all study centres (No. 2020BZYLL0803). Written informed consent will be obtained from enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100044585 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 24 March 2021); preresults.

Acupuncture inhibits mammalian target of rapamycin, promotes autophagy and attenuates neurological deficits in a rat model of hemorrhagic stroke.

BACKGROUND: Intracerebral hemorrhage (ICH) accounts for approximately 15% of all stroke cases. Previous studies suggested that acupuncture may improve ICH-induced neurological deficits. Therefore, we investigated the effects of acupuncture on neurological deficits in an animal model of ICH. METHODS: Adult male Sprague-Dawley rats were injected with autologous blood (50 µL) into the right caudate nucleus. Additional rats underwent sham surgery as controls. ICH rats either received acupuncture (GV20 through GB7 on the side of the lesion) or sham acupuncture (1 cm to the right side of the traditional acupuncture point locations). Some ICH rats received acupuncture plus rapamycin injection into the right lateral ventricle. Neurological deficits in the various groups were assessed based on composite neurological score. The perihemorrhagic penumbra was analyzed by histopathology following hematoxylin-eosin staining. Levels of autophagy-related proteins light chain (LC)3 and p62 as well as of mammalian target of rapamycin (mTOR)-related proteins, and phosphorylated (p)-mTOR and p-S6K1 (ribosomal protein S6 kinase beta-1), were assessed by Western blotting. RESULTS: Acupuncture significantly improved composite neurological scores 7 days after ICH (17.7 ± 1.49 vs 14.8 ± 1.32, p < 0.01). Acupuncture augmented autophagosome and autolysosome accumulation based on transmission electron microscopy. Acupuncture significantly increased expression of LC3 (p < 0.01) but decreased expression of p62 (p < 0.01). Acupuncture also reduced levels of p-mTOR and p-S6K1 (both p < 0.01). CONCLUSION: Acupuncture improved neurological deficits in a rat model of ICH, possibly by inhibiting the mTOR pathway and activating autophagy.

Efficacy of acupuncture for sciatica: study protocol for a randomized controlled pilot trial.

BACKGROUND: Acupuncture is widely used for pain diseases while evidence of its efficacy for sciatica is insufficient. We aim to explore the feasibility and efficacy of acupuncture with different acupoint selecting strategies for sciatica induced by lumbar disc herniation. METHODS: This is a multicenter, three-arm, patient-assessor-blinded randomized controlled pilot trial. Ninety patients will be assigned randomly into 3 groups including disease-affected meridians (DAM) group, non-affected meridians (NAM) group, and sham acupuncture (SA) group in a 1:1:1 ratio. The trial involves a 4-week treatment along with follow-up for 22 weeks. The primary outcome is the change of leg pain intensity measured by the visual analogue scale (VAS) from baseline to week 4 after randomization. Secondary outcomes include functional status, back pain intensity, and quality of life. Adverse events will also be recorded. DISCUSSION: The results will inspire the optimal acupuncture strategy for sciatica and help establish a better design as well as power calculation for a full-scale study. TRIAL REGISTRATION: ChiCTR2000030680 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 9 March 2020).

Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis.

BACKGROUND: Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia-reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. METHODS: Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), and Qubin (GB7) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. RESULTS: Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. CONCLUSIONS: Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

[Effect of acupuncture on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage].

OBJECTIVE: To observe the effect of acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage (ICH), and to explore the action mechanism of acupuncture on promoting the recovery of neural function in rats with ICH. METHODS: Forty SPF six-week-old male SD rats were randomly divided into a sham operation group, a model group, a non-acupoint group and an acupuncture group, 10 rats in each group. The rats in the model group, non-acupoint group and acupuncture group were intervened with autologous blood injection to prepare ICH model, while the rats in the sham operation group were only intervened with operation but not injection with autologous blood. About 3 hours after the establishment of the model, the rats in the acupuncture group were intervened with acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7), once every 12 hours, for 7 days; the rats in the non-acupoint group were intervened with acupuncture at the non-acupoint [parallel to the "Baihui" (GV 20), 1 cm next to the midline] on the affected side, and other treatment was the same as the acupuncture group. At the end of the intervention, the composite nerve function score of each group was evaluated; the histomorphology of the hemorrhage penumbra was observed by HE staining; the expression of NLRP3 inflammatory corpuscle in the brain was detected by immunohistochemistry; the relative protein expression levels of NLRP3, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in brain were detected by the method of Western blot. RESULTS: Seven days into intervention, compared with the sham operation group, each item score and total score of composite nerve function in the model group were significantly reduced (P<0.01, P<0.05). There was edema and karyopyknosis in brain neuron as well as necrocytosis and inflammatory cell infiltration in the model group. Compared with the model group and the non-acupoint group, the total score of composite nerve function and the scores of symmetrical movement of limbs (LS) and proprioception of tentacles (VP) in the acupuncture group were increased (P<0.01, P<0.05), and the cell necrosis and inflammatory cell infiltration were relieved. Compared with the sham operation group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1ß and IL-18 in brain tissue in the model group were increased (P<0.01); compared with the model group and the non-acupoint group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1ß and IL-18 in brain tissue in the acupuncture group were reduced (P<0.01). CONCLUSION: Acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) could downregulate the expression of NLRP3, IL-1ß and IL-18 in the brain tissue of ICH rats, inhibit the inflammatory response, and promote the recovery of neural function.

[Penetrative needling of scalp-points improves neurological function by promoting stem cell proli-feration and activating Shh/Gil1 signaling in intracerebral hemorrhage rats].

OBJECTIVE: To observe the effect of penetrative needling from "Baihui" (GV20) to "Qubin" (GB7) on neural stem cell proliferation and sonic hedgehog (Shh) signaling in subventricular zone (SVZ) in intracerebral hemorrhage (ICH) rats so as to explore its mechanisms underlying improvement of ischemic injury of brain. METHODS: Male SD rats were randomly divided into blank control, model, acupuncture and agonist (Purmorphamine, an activator of Shh signaling pathway) groups (n＝18 in each group, 6 for H．E. stain, 6 for examining neuronal cell proliferation, and 6 for immunohistochemistry). The ICH model was established by injecting autogenous blood (50 µL) into the right caudate nucleus. The neurological defect was scored with refe-rence to Bederson's method. Penetrative needling from GV20 to GB7 was performed by manipulating the needle for 6 min (repeated 3 times in 30 min), once daily for 7 days. Intraperitoneal injection of Purmorphamine (1 mg/mL, 1 mg/kg) was performed, once daily for 7 days. Histopathological changes of the hemorrhagic penumbra region were observed under microscope after H．E. stain, the newborn neural stem cell proliferation (BrdU＋/Nestin＋ double labeled cells) in the SVZ was observed by immunofluorescence after intraperitoneal injection of BrdU (50 mg/kg), and the expression of Shh and glioma-associated hemolog-1 (Gli1) detected by immunohistochemistry. RESULTS: After modeling, the neurological score and expression levels of Shh and Gil1 proteins were significantly increased in the model group relevant to the blank control group (P<0.001). Following the interventions, the neurological score was evidently decreased (P<0.05), while the number of BrdU＋/Nestin＋ double labeled cells and the expression levels of Shh and Gil1 proteins were significantly increased in both acupuncture and agonist groups in comparison with the model group (P<0.001). No significant differences were found between the acupuncture and agonist groups in down-regulating the neurological score and in up-regulating the number of BrdU＋/Nestin＋ double labeled cells and the expression of Shh and Gil1 proteins (P>0.05). Outcomes of H．E. stain showed obvious edema, disordered arrangement of cells, infiltration of inflammatory cells and red blood cells with glial cell hyperplasia around the hematoma area in the model group, which was relatively milder in both acupuncture and agonist groups such as in basic disappearance of edema and inflammatory reaction. CONCLUSION: Penetrative needling from GV20 to GB7 can obviously improve neurological function in ICH rats, which is related to its effects in activating Shh/Gil1 signaling and in further promoting neural stem cell proliferation in the SVZ region.

[Penetrative needling improves neurological function by up-regulating expression of autophagy related protein LC3 in rats with hemorrhagic stroke].

OBJECTIVE: To observe the effect of penetrative needling from "Baihui" (GV20) to "Qubin" (GB7) on neurological function and expression of autophagy related protein microtubule-associated protein, light chain 3 (LC3) in rats with hemorrhagic stroke, so as to explore its mechanism underlying improvement of hemorrhagic stroke. METHODS: A total of 120 male SD rats were randomly divided into sham operation, model, non-acupoint, acupuncture and medication (Rapamycin) groups which were further divided into two time-point subgroups (3, 7 days after modeling, n=12/subgroup). The intracerebral hemorrhage model was established by injection of the rat's auto-blood (50 µL) into the putaman region. Penetrative needling from GV20 to GB7 or sham acupoints (about 1 cm beside GV20 and GB7) was conducted for 30 min, twice daily for 7 days. For rats of the medication group, Rapamycin solution (7 µmol/L) was injected into the right lateral ventricle. The neurological functions (locomotor and balance deficits) were evaluated according to suspended wire test (0-6 points) and horizontal board walking test (0-6 points). Immunohistochemistry and Western blot were used to detect the expression of total LC3 and expression of LC3-Ⅰ and LC3-Ⅱ proteins in the ischemic penumbra region of brain tissue, respectively. RESULTS: After modeling, the neurological function scores were significantly decreased on day 3 and 7, the levels of LC3-Ⅱ/Ⅰ and LC3 protein on day 3 and 7 were significantly increased in the model group relevant to the sham operation group (P<0.05). Following the interventions, the neurological function scores as well as LC3-Ⅱ/Ⅰ and LC3 protein expression were significantly increased in both acupuncture and medication groups compared with the model group (P<0.05). The effect of Rapamycin was obviously stronger than that of penetrative needling in up-regulating the expression of LC3-Ⅱ/Ⅰ and LC3 protein (P<0.05). CONCLUSION: Penetrative needling can improve neurologic function in hemorrhagic stroke rats, which is related with its effect in up-regulating the expression of autophagy-related protein LC3.

Baihui (DU20)-penetrating-Qubin (GB7) acupuncture inhibits apoptosis in the perihemorrhagic penumbra.

Baihui (DU20)-penetrating-Qubin (GB7) acupuncture can inhibit inflammatory reactions and activate signaling pathways related to proliferation after intracerebral hemorrhage. However, there is no research showing the relationship between this treatment and cell apoptosis. Rat models of intracerebral hemorrhage were established by injecting 60 µL of autologous blood into the right side of the caudate-putamen. Six hours later, the needle traveled subcutaneously from the Baihui acupoint to Qubin acupoint. The needle was alternately rotated (180 ± 10 turns/min) manually along clockwise and counter-clockwise directions. Stimulation lasted for 7 days, and was performed three times each for 6 minutes with 6-minute intervals between stimulations. Rats intraperitoneally receiving Sonic hedgehog pathway activator, purmorphamine (1 mg/kg per day), served as positive controls. Motor and sensory function were assessed using the Ludmila Belayev test. Extent of pathological changes were measured in the perihemorrhagic penumbra using hematoxylin-eosin staining. Apoptosis was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. Expression of smoothened (Smo) and glioma-associated homolog 1 (Gli1) was determined by western blot assay. Our results showed that Baihui-penetrating-Qubin acupuncture promoted recovery of motor and sensory function, reduced the apoptotic cell percentage in the perihemorrhagic penumbra, and up-regulated Smo and Gli1 expression. We conclude that Baihui-penetrating-Qubin acupuncture can mitigate hemorrhage and promote functional recovery of the brain in a rat model of intracerebral hemorrhage, possibly by activating the Sonic hedgehog pathway.

Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke.

BACKGROUND: Hemorrhagic stroke accounts for approximately 15% of all stroke cases, and is associated with high morbidity and mortality. Limited human studies suggested that scalp acupuncture could facilitate functional recovery after cerebral hemorrhage. In the current study, we used an animal model of cerebral hemorrhage to examine the potential effects of scalp acupuncture. METHODS: Adult male Sprague-Dawley rats received autologous blood (50µL) into the right caudate nucleus on the right side under pentobarbital anesthesia, and then received scalp acupuncture (DU20 through GB7 on the lesion side) or sham acupuncture (1cm to the right side of the acupoints) (n=10 per group). A group of rats receiving autologous blood into the caudate nucleus but no other intervention, as well as a group of rats receiving anesthesia but no blood injection to the brain (n=10 per group) were included as additional controls. Composite neuroscore, corner turn test, forelimb placing test, wire hang task and beam walking were used to evaluate the behavior of rats. Hematoxylin and Eosin (HE) staining was used to observe the histopathological changes. Western blot was used to detect the content of tumor necrosis factor alpha (TNF-α) and nuclear factor-KappaB (NFκB) protein expression. RESULTS: Scalp acupuncture attenuated neurological deficits (p<0.01 or <0.05 vs. sham acupuncture using a variety of behavioral tests) at 1-7days after the treatment. The brain content of TNF-α and NFκB was decreased (p<0.01 for both). CONCLUSIONS: Scalp acupuncture could improve neurological deficits in a rat model of hemorrhagic stroke.