Effects of Patient-Controlled Transcutaneous Electrical Acupoint Stimulation on Cancer Induced Bone Pain Relief in Patients with Non-Small Cell Lung Cancer: Study Protocol for a Randomized Controlled Trial.

Background: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC). Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight. Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP. Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.

Transcutaneous electrical acupoint stimulation for cancer-related pain management in patients receiving chronic opioid therapy: a randomized clinical trial.

PURPOSE: The opioid crisis resulting from its use disorder and overdose poses additional challenges for cancer pain management. The American Society of Clinical Oncology Practice Guideline recommends acupuncture therapy for the management of adult cancer-related pain (CRP), but the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on CRP remains uncertain. METHODS: This 5-week prospective randomized clinical trial was conducted at 2 hospitals in China, and participants with CRP receiving chronic opioid therapy were randomized 1:1 into two groups between December 2014 and June 2018. The true TEAS group underwent 15 sessions of TEAS treatments over 3 consecutive weeks, while the control group received sham stimulation. The primary outcome was the numerical rating scale (NRS) score in the past 24h at week 3. The secondary outcomes included morphine equivalent daily dose, quality of life and adverse events. RESULTS: A total of 159 participants were included in the modified intention-to-treat population. The baseline characteristics were similar in both groups. The mean NRS scores were 0.98 points at week 3 in the true TEAS group and 1.41 points in the sham group, with the mean difference between groups of -0.43 points (P < 0.001; OR = 0.68, P < 0.05). The proportion of patients with NRS reduction more than thirty percentage at week 3 was 50.00% in the true TEAS group and 35.44% in the sham group (RD = 0.15, P > 0.05; RR = 1.41, P > 0.05). No significant difference in pain intensity between the two groups was observed during the follow-up period without TEAS intervention (week 4, OR = 0.83, P > 0.05; week 5, OR = 0.83, P > 0.05). The Karnofsky Performance Status value suggested that patients in the true TEAS group experienced an improved quality of life (Between-group differences: week 3, 3.5%, P < 0.05; week 4, 4.6%, P < 0.001; week 5, 5.6%, P < 0.001). CONCLUSIONS: The 3-week application of TEAS in patients with CRP receiving chronic opioid therapy resulted in a statistically significant reduction in pain scores, but the observed reduction was of uncertain clinical significance. The prolonged analgesic effect of TEAS was not confirmed in this trial. CLINICALTRIAL: GOV: ChiCTR-TRC-13003803.

ß-Elemene Improves Morphine Tolerance in Bone Cancer Pain via N-Methyl-D-Aspartate Receptor 2B Subunit-Mediated µ-Opioid Receptor.

Background: Improving morphine tolerance (MT) is an urgent problem in the clinical treatment of bone cancer pain. Considering that ß-Elemene is widely used in the treatment of cancer pain, we explored the effects and mechanism of ß-Elemene in preventing MT of bone cancer pain. Method: Bone cancer pain and chronic MT rat model was established by injecting MADB106 cells and morphine (10 mg/kg). SH-SY5Y cells were treated with morphine (10 µg/mL) for 48 h to establish a cell model. The mechanical withdrawal threshold and thermal withdrawal latency of rats were detected by mechanical allodynia and thermal hyperalgesia tests, respectively. The protein expressions of µ-opioid receptor (MOPR), cyclic adenosine monophosphate (cAMP), N-methyl-D-aspartate receptor subunit 2B (NR2B), phosphorylated-calmodulin-dependent protein kinase II (p-CaMKII), and CaMKII were detected by western blot. The viability of SH-SY5Y cells was determined by the cell counting kit-8 assay. cAMP content in SH-SY5Y cells was measured by a LANCE cAMP kit. Result: Animal experiments showed that MT strengthened over time, while increased ß-Elemene dosage alleviated MT. The viability of SH-SY5Y cells was down-regulated by high-dose ß-Elemene. In the rat and cell models, long-term morphine treatment decreased the expression of MOPR and increased the cAMP and NR2B expressions and p-CaMKII/CaMKII, while ß-Elemene and siNR2B counteracted the effects of morphine treatment. In addition, siNR2B reversed the effects of ß-Elemene on related protein expressions and cAMP content in the cell model. Conclusion: ß-Elemene improved MT in bone cancer pain through the regulation of NR2B-mediated MOPR.

An mRNA sequencing analysis of the healing-promoting role of electroacupuncture a in rat skin wound model.

BACKGROUND: Many studies have confirmed that electroacupuncture can regulate the body's environment to treat a variety of diseases. However, there are few reports on the mechanism of electroacupuncture therapy for diseases involving skin injury. Transcriptome sequencing can reveal changes in gene expression within cells and the signaling pathways involved. In this study, we used transcriptome sequencing to study the molecular mechanisms by which electroacupuncture promotes the healing of skin lesions. METHODS: A total of 10 SD rats were divided into two groups of 5: a control group and an electroacupuncture treatment group. The wound-healing area was compared between the two groups after 3 and 14 days. Then, mRNA sequencing and bioinformatics were used to analyze the changes in gene expression profiles in skin tissue after electroacupuncture stimulation. RESULTS: (I) The wound area was significantly reduced after 3 and 14 days of electroacupuncture compared with the control group (P<0.05). (II) There was a total of 694 gene expression changes, 496 of which were upregulated and 198 of which were downregulated. Analysis of variable gene-related signaling pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), identified immuneinflammatory response, cell proliferation, tissue remodeling, cell metabolism, graft-versus-host disease, antigen processing and presentation, Th17 cell differentiation, cytokine-cytokine receptor interaction, PPAR signaling pathway, Wnt signaling pathway and other signaling pathways were changed. CONCLUSIONS: Electroacupuncture can promote wound repair, as shown by the changes in gene expression profiles during the healing of skin wounds under electroacupuncture. This study provides a scientific basis that deepens the understanding of the mechanism underlying electroacupuncture.

The Mechanism of MAPK Signal Transduction Pathway Involved with Electroacupuncture Treatment for Different Diseases.

The mitogen-activated protein kinase (MAPK) signal transduction pathway plays an important role in the regulation of various diseases, such as cardiovascular and cerebrovascular diseases, and takes part in anti-inflammatory effects, analgesic effects, protection against injury, and maintenance of gastrointestinal functions. Electroacupuncture therapy is an external therapy used in traditional Chinese medicine. By adding external electrical stimulation to traditional acupuncture, the stimulus gets doubled and the therapeutic efficacy gets enhanced accordingly. It combines the benefits of both acupuncture and electrical stimulation. In recent years, some studies have explored the molecular mechanisms of MAPK signal pathways involved with electroacupuncture treatment. Based on these recent studies, this article summarizes the mechanisms of MAPK signal transduction pathways involved with electroacupuncture treatment. This adds great value to the studies of molecular mechanisms of electroacupuncture treatment and also provides an effective reference for its clinical use.

Evaluating the analgesic effect and advantage of transcutaneous electrical acupoint stimulation combined with opioid drugs for moderate to severe cancer-related pain: a study protocol for a randomized controlled trial.

BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS), which is also known as acupuncture-like transcutaneous electrical nerve stimulation (TENS), has been widely used in acute or chronic pain. However, previous research has not demonstrated that TEAS is effective for cancer-related pain. Opioid drugs are strongly recommended for treating cancer-related pain, but opioid-induced immunosuppression is still the most intractable drug-induced medical problem. Evaluating the efficacy and potential advantage of TEAS combined with opioid drugs in moderate and severe cancer-related pain in China is important because such studies are lacking. METHODS/DESIGN: This trial is a multicenter, prospective randomized controlled clinical trial. In total, 160 patients who were enrolled from two hospitals in the Zhejiang Province (China) will be randomly allocated into two groups: a TEAS group and sham TEAS group without acupoint electrical stimulation. Both groups will receive a 21-day interval of chemotherapy and conventional cancer pain therapy. Fifteen treatment sessions will be performed over a three-week period. The primary outcomes will be measured by changes in the Numerical Rating Scale (NRS) scores and equivalent dosage of morphine at baseline, three weeks of treatment and one two-week follow-up. The secondary outcome measures include cellular immunity function, life quality assessment, opioids side effects assessment, and safety and compliance evaluation. DISCUSSION: This trial is expected to clarify whether TEAS is effective for cancer-related pain. These results demonstrate the advantage of TEAS combined with opioid drugs on improving immune function and decreasing opioid induced side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-13003803 . Registered on 27 August 2013.

[Impacts on analgesia and detumescence in ankle sprain treated with acupuncture at Xiaojie point combined with tendon-regulation manipulation].

OBJECTIVE: To compare the efficacy difference of analgesia and detumescence on ankle sprain among acupuncture at Xiaojie point combined with tendon regulation manipulation, acupuncture at Xiaojie point and tendon regulation manipulation. METHODS: Sixty cases of ankle sprain were randomized into a combined therapy group, a Xiaojie point group and a tendon-regulation manipulation group, 20 cases in each one. The combined therapy of acupuncture at Xiaojie point and tendon regulation manipulation, the acupuncture at Xiaojie point and the simple application of tendon-regulation manipulation were applied respectively in the three groups, once a day, 3 treatments were required. The symptom score such as pain, ecchymosis, swelling and motor dysfunction and the total score were observed before and after treatment in the three groups. The different values of pain and swelling scores were compared before and after treatment in the three groups. The efficacy was compared among the groups. RESULTS: The total effective rate was 100.0% (20/20) in each group. But the curative rate was 85.0% (17/20) in the combined group, 65.0% (13/20) in the Xiaojie point tion manipulation group. After treatment, the symptom scores of pain, ecchymosis, swelling and motor dysfunction and the total score were all improved as compared with those before treatment in the three groups (P < 0.01, P < 0.05). The pain score in either the combined therapy group or Xiaojie point group was lower than that in the tendon-regulation manipulation group after treatment (0.20 -/+ 0.41, 0.15 +/- 0.37 vs 0.60 +/- 0.50, both P < 0.05). Swelling score in the Xiaojie point group was different significantly from that in the tendon-regulation manipulation 0.49 vs 06.4 vs. 20+0.41, P < 0.05). The different value of pain score in either the combined therapy group or Xiaojie point group was higher than that in the tendon-regulation manipulation group before group after treatment (0.65 bined therapy group or Xiaojie point group was higher than that in the tendon-regulation manipulation group before and after treatment (2.35 +/- 0.59, 2.45 +/- 0.51 vs 2.00 +/- 0.46, both P < 0.05). The different value of swelling score in the tendon-regulation manipulation group was higher than that in the Xiaojie point group before and after treatment (2.30 +/- 0.57 vs 1.60 +/- 0.60, P < 0.05). CONCLUSION: Acupuncture at Xiaojie point combined with tendon-regulation manipulation achieve an apparent effect of analgesia and detumescence on ankle sprain.