Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats. / S1脑区CXCL1/CXCR2å‚ä¸Žé’ˆåˆºæ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ç—›çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

Global trends of acupuncture clinical research on analgesia from 2010 to 2023: a bibliometric and visualization analysis.

Objective: Acupuncture, acknowledged as a potent non-pharmacological therapy, is frequently employed to alleviate pain. Despite its widespread use, there has been a lack of overarching bibliometric analysis of clinical research on acupuncture analgesia. We aimed to summarize current patterns, hotspots, and development trends in this field through bibliometric analysis. Methods: This study evaluates academic publications retrieved from the Web of Science database (2010.01-2023.09) concerning acupuncture analgesia in clinical settings. All primary and secondary studies on humans were included. To track global developmental trends, we employed several software for analyzing annual publication volumes, countries/regions, institutions, authors, cited authors, journals, cited journals, references, and keywords and to draw collaborative networks and reference co-citation network maps. Results: The final search encompassed 7,190 relevant studies, including 1,263 randomized controlled trials (RCTs) and 1,293 systematic reviews and meta-analyses. The results indicated a gradual increase in the number of annual publications on acupuncture analgesia in clinical practice. Among countries and institutions, China (2,139) and Chengdu University of Traditional Chinese Medicine (258) ranked first. Liang FR (89 articles) was the most prolific author, while MacPherson H (604) was the most cited author. MEDICINE (455) was the most productive journal, and Pain (2,473/0.20) ranked first in both the frequency and centrality of cited journals. Notably, the most frequently cited reference was a systematic review of individual patient data on acupuncture carried out for chronic pain that was published by Vickers Andrew J in 2012 (156). Burst analysis identified frontier research areas for 2010-2020, encompassing network meta-analysis, case reports, dry needling, lumbar disc herniation, cancer, post-herpetic neuralgia, insomnia, and bibliometric analysis. Conclusion: This study outlines current trends and potential future research hotspots in clinical acupuncture analgesia over the past decade. Findings emphasize the necessity for enhanced international collaboration to improve research output and translation.

To assess the analgesic efficacy of adjuvant magnesium sulfate added with ropivacaine over ropivacaine alone as a continuous infiltration in total abdominal hysterectomy wound: A randomized controlled trial.

Background and Aims: Magnesium sulfate (MgSO4) has been demonstrated to have analgesic property in various clinical settings. This study explores if addition of MgSO4 to ropivacaine increases its analgesic efficacy when infiltrated continuously in the postsurgical wound following total abdominal hysterectomy. Material and Methods: This randomized controlled trial was conducted at a tertiary care referral hospital in New Delhi, India. Fifty-two patients were randomized into two groups to receive the intervention of which 48 were able to complete the study. The first group (n = 26) received 0.25% ropivacaine infiltration and the second group (n = 26) received 0.25% ropivacaine with 5% MgSO4 at the incision site for 48 h postoperatively. Primary objective was to compare the total postoperative opioid (morphine) consumption by the study participants in both the groups and the secondary objectives were pain scores at rest and at movement, patient satisfaction score, and wound quality of life on the 7th postoperative day among the two groups. Results: Both the groups were comparable in their demographic characteristics. The median morphine consumed at 48 h postoperatively was 16.5 [0-77] mg in the ropivacaine group and 13[1-45] mg in the ropivacaine with MgSO4 group and the difference was statistically insignificant (P = 0.788). There was no statistical difference between the groups with respect to the pain scores, patient satisfaction, or wound quality of life at 7 days. Conclusion: The addition of MgSO4 to ropivacaine does not confer any additional postoperative analgesic benefits over ropivacaine alone in continuous wound infiltration following total abdominal hysterectomy.

Effect of "needle sensation" and the real-time changes in autonomic nervous system activity during acupuncture analgesia.

Introduction: Acupuncture analgesia (AA) is widely used in clinical practice. The autonomic nervous system (ANS) may be an important pathway for acupuncture signal transduction. However, real-time changes in autonomic function during AA and the effect of "needle sensation" remain unclear. Methods: We established a human pain model in healthy adults and randomly assigned 128 participants to the model, sham acupuncture, and acupuncture groups in a 1:1:2 ratio. Heart rate variability (HRV), including total power (TP), low-frequency power (LF), high-frequency power (HF), ratio of LF to HF (LF/HF), standard deviation of the normal-normal intervals (SDNN), and root mean square of successive interval differences (RMSSD), were used to assess autonomic function. The visual analog scale (VAS) and efficiency were used to assess the analgesic effect of acupuncture. The Massachusetts General Hospital acupuncture sensation scale (MASS) was used to indicate the intensity of the needle sensation. Anxiety levels were also measured. Finally, the correlation of MASS with HRV, VAS, and anxiety levels was analyzed. Results: VAS decreased after 10 min of needling and 5 min after needle withdrawal in the acupuncture group compared with those in the model group (p = 0.038, p = 0.020). The efficacy rates were 82.0, 50.0, and 61.3% in the acupuncture, model, and sham groups, respectively. These represent significant differences between the acupuncture group and the model and sham acupuncture groups (p < 0.001 in each case). No differences were observed between the model and sham acupuncture groups. HF, TP, SDNN, and RMSSD were all increased in the acupuncture group compared with those in the model group (p = 0.045, p = 0.041, p = 0.002, p = 0.006, respectively). No differences were observed in the sham acupuncture group compared to the model group (p = 0.632, p = 0.542, p = 0.093, p = 0.222, respectively). The LF and LF/HF did not differ among all three groups. A positive correlation was observed between MASS and RMSSD2, LF2, RMSSD4, TP4, VAS5, and anxiety levels. Conclusion: AA was associated with enhanced vagal activity. The intensity of needle sensation was positively correlated with vagal and sympathetic nerve activities. Acupuncture is an effective means of regulating autonomic function, and needle sensation may be an important modulator.

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.

Treating Lateral Epicondylopathy With Dry Needling and Exercise: A Case Series.

CONTEXT: Lateral epicondylopathy (LE) is a common overuse injury affecting elbow, wrist, and hand function. It is characterized by weakness and pain in the muscles and tendons of the forearm responsible for the extension of your wrist and fingers. Trigger point dry needling is a technique reported to be beneficial in managing pain and dysfunction after LE diagnosis. LE is also commonly treated with conservative treatment, such as joint and soft tissue mobilization, self-care home programs, and anti-inflammatory use. We explored a different dry needling approach consisting of in situ dry needling with electric stimulation combined with targeted therapeutic exercise to treat LE in 3 cases. CASE PRESENTATION: Three patients were referred for dry needling once a week for 6 weeks and home-based exercise therapy for LE. They were clinically evaluated using grip strength, a visual analog scale to assess pain, and Patient-Rated Tennis Elbow Evaluation Test scores. These were measured at 4 time points (weeks 0, 2, 4, and 6). MANAGEMENT AND OUTCOMES: The dry needling intervention incorporated 8 locations in the upper-extremity with 2 electric stimulation channels. The patients had reduced pain as measured by a visual analog scale, increased function as measured by the Patient-Rated Tennis Elbow Evaluation Test, and increased grip strength over 6 weeks. CONCLUSIONS: This case series illustrates the use of dry needling and a home exercise program to provide a favorable outcome in a patient with LE. Patients had an 80% to 100% reduction in pain and similar improvements in function that were significantly beyond the minimum clinically important difference. This dry needling approach is a safe and effective treatment of LE in the short term.

Ketamine intolerance in patients on enhanced recovery after surgery protocols undergoing colorectal operations.

BACKGROUND: Ketamine is used in enhanced recovery after surgery (ERAS) protocols because of its beneficial antihyperalgesic and antitolerance effects. However, adverse effects such as hallucinations, sedation, and diplopia could limit ketamine's utility. The main objective of this study was to identify rates of ketamine side effects in postoperative patients after colorectal surgery and, secondarily, to compare short-term outcomes between patients receiving ketamine analgesia and controls. METHODS: This was a retrospective observational cohort study. Subjects were adults who underwent ERAS protocol-guided colorectal surgery at a large, integrated health system. Patients were grouped into ketamine-receiving and preketamine cohorts. Patients receiving ketamine were divided into tolerant and intolerant groups. Propensity score-adjusted models tested multivariate associations of ketamine tolerance/intolerance vs control group. RESULTS: A total of 732 patients underwent colorectal surgery within the ERAS program before ketamine's introduction (control). After ketamine's introduction, 467 patients received the medication. Intolerance was seen in 29% of ketamine recipients, and the most common side effect was diplopia. Demographics and surgical variables did not differ between cohorts. Multivariate models revealed no significant differences in hospital stays. Pain scores in the first 24 hours after surgery were slightly higher in patients receiving ketamine. Opiate consumption after surgery was lower for both ketamine tolerant and ketamine intolerant cohorts than for controls. CONCLUSION: Rates of ketamine intolerance are high, which can limit its use and potential effectiveness. Ketamine analgesia significantly reduced opiate consumption without increasing hospital stays after colorectal surgery, regardless of whether it was tolerated.

Effectiveness and safety of auricular acupuncture on adjuvant analgesia in patients with total knee arthroplasty: a randomized sham-controlled trial.

Objective: This study aimed to evaluate the effectiveness and safety of auricular acupuncture (AA) on postoperative analgesia, the degree of postoperative nausea, and the effect of inflammation after total knee arthroplasty (TKA). Methods: This was a single-center, placebo-controlled, randomized clinical trial. In total, 96 patients were randomly divided into an AA group with an indwelling intradermal needle (n = 48) and a sham auricular acupuncture (SAA) group with a non-penetrating placebo needle (n = 48). Intra-spinal anesthesia was adopted in both groups during surgery, and an epidural analgesic pump was implanted after surgery for 48 h. The primary outcome was the post-surgery visual analog score (VAS) of resting and movement states (at 6, 12 h and 1, 2, 3, 5, and 7 days). The secondary outcomes included additional doses of analgesic injection during the treatment, C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count on the 1st, 3rd, and 7th day after the operation, nausea on the 1st, 2nd, and 3rd day after the operation, the Hospital for Special Surgery Knee Score (HSS) on the 2nd and 12th week after the operation, and adverse events. Results: The VAS in the AA group at 6 h, 12 h, 2, 3, and 5 days after surgery were lower than those of the SAA group (p < 0.05). Among the secondary outcomes, the total dose of additional analgesic injection after surgery in the AA group was lower than that in the SAA group (p < 0.05). The serum CRP on the 1st day after operation in the AA group was lower than that in the SAA group (p < 0.05). The degree of nausea on 2nd day after surgery in the AA group was lower than that in the SAA group (p < 0.05). There was no significant difference in other outcomes (p > 0.05). Conclusion: In this study, AA was shown to be an effective and safe complementary and alternative therapy for pain relief after TKA, which was able to reduce the total postoperative dose of additional painkillers, decrease serum CRP 1 day after surgery, and improve the degree of postoperative nausea. Clinical trial registration: www.chictr.org.cn, ChiCTR2100054403.

TRPA1 Ion Channel Mediates the Analgesic Effects of Acupuncture at the ST36 Acupoint in Mice Suffering from Arthritis.

Purpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia. Patients and Methods: We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1. Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated. Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.

The value of local dexmedetomidine as an adjuvant to ultrasound-guided wide awake local anesthesia no tourniquet (WALANT) in flexor tendon repair surgeries: a randomized controlled trial.

BACKGROUND: The Wide-Awake Local Anesthesia No Tourniquet (WALANT) technique allows intraoperative motor assessment of tendon repair integrity of the hand compared with general anesthesia or brachial plexus block. No studies have tested the effect of adding dexmedetomidine to lidocaine on the analgesic properties of the WALANT technique, which is the aim of our study. METHODS: A total of 128 patients aged more than 18 years were scheduled for surgical flexor tendon injury repair using WALANT technique. Patients were divided into two equal groups. Ultrasound-guided subcutaneous injection of lidocaine 1% with dexmedetomidine (1 µg/kg), Group D, or without dexmedetomidine, Group C, was performed at four points: proximal to the wrist joint, the distal forearm, palm region, and proximal phalanges. The primary outcome was total morphine consumption throughout the first postoperative day. Secondary outcomes included number of patients requiring rescue analgesia, time to first analgesic request, and pain score. RESULTS: Total morphine consumption was significantly (P < 0.001) lower in group D (2.66 ± 0.998) than in group C (3.66 ± 1.144) mg. Number of patients requiring rescue analgesia was significantly (P < 0.001) lower in group D (54.7% (35)) than group C (100.0% (64)). The time for first request for analgesia was significantly (P < 0.001) longer in group D (11.31 ± 6.944) than in group C (5.91 ± 4.839) h. Pain score was significantly higher in group C than D at three (P < 0.001), and six (P = 0.001) hours (P = 0.001) postoperatively. CONCLUSION: Dexmedetomidine significantly improves the analgesic quality of WALANT when added to lidocaine with less opioid consumption. TRIAL REGISTRATION: (ID: PACTR202203906027106; Date: 31/07/2023).

Targeted local anesthesia: a novel slow-release Fe3O4-lidocaine-PLGA microsphere endowed with a magnetic targeting function.

PURPOSE: Lidocaine microspheres can prolong the analgesic time to 24-48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. METHODS: Fe3O4-lidocaine-PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. RESULTS: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 µm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4-Lidocain-PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. CONCLUSION: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting.

Understanding of Spinal Wide Dynamic Range Neurons and Their Modulation on Pathological Pain.

The spinal dorsal horn (SDH) transmits sensory information from the periphery to the brain. Wide dynamic range (WDR) neurons within this relay site play a critical role in modulating and integrating peripheral sensory inputs, as well as the process of central sensitization during pathological pain. This group of spinal multi-receptive neurons has attracted considerable attention in pain research due to their capabilities for encoding the location and intensity of nociception. Meanwhile, transmission, processing, and modulation of incoming afferent information in WDR neurons also establish the underlying basis for investigating the integration of acupuncture and pain signals. This review aims to provide a comprehensive examination of the distinctive features of WDR neurons and their involvement in pain. Specifically, we will examine the regulation of diverse supraspinal nuclei on these neurons and analyze their potential in elucidating the mechanisms of acupuncture analgesia.

Hypnosis during Endovascular Abdominal Aortic Aneurysm Repair.

(1) Background: Endovascular abdominal aneurysm repair (EVAR) is associated with a reduction in early morbidity and mortality compared with open repair. Procedures performed under hypnosis might represent an alternative to further reduce the risks related to general anesthesia (GA). This study aimed to assess the feasibility and safety of hypnosis and local anesthesia during EVAR. (2) Methods: All consecutive patients who underwent EVAR or fenestrated/branched EVAR (f/bEVAR) under hypnosis and local anesthesia (n = 28) between 2017 and 2019 were retrospectively studied and matched to control patients who underwent the same interventions under GA. (3) Results: There was neither a significant difference in the length of ICU stay (p = 0.06), nor in the occurrence of endoleaks, reintervention, and 30-day mortality rate (p = 1.00, 0.73, and 0.24, respectively). The hypnosis group had lower use of norepinephrine (maximum dose 0.04 ± 0.1 vs. 1.2 ± 4.0 mg·h-1, p < 0.001), shorter procedure duration (181.2 ± 71.4 vs. 214.3 ± 79.6 h, p = 0.04), and shorter length of stay (5.4 ± 3.2 vs. 8.4 ± 5.9 days, p = 0.002). (4) Conclusions: In this pioneering study, hypnosis during EVAR appears feasible and safe. It is associated with lower intraoperative use of norepinephrine, as well as procedure duration and length of in-hospital stay.

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

Systematic Reviews and Synthesis without Meta-Analysis on Hydrotherapy for Pain Control in Labor.

BACKGROUND: Although there is scientific evidence regarding the use of water immersion during labor, this evidence is primarily focused on the first stage of labor. There is limited scientific evidence on water immersion during the second stage of labor. OBJECTIVE: The objective of this study was to conduct a comprehensive systematic review and synthesis of contemporary evidence related to water birth, with a specific focus on the second stage of labor. METHODS: A systematic review of the scientific literature published between January 2018 and October 2023 was carried out. A synthesis of the results was conducted following the Synthesis without Meta-Analysis (SWiM) guidelines. PubMed, Scopus, and the Cochrane Library were utilized as information sources. The search strategy was designed using the keywords "immersion" and "parturition", along with their relevant synonyms. Inclusion criteria encompassed studies employing randomized controlled trials (RCTs), systematic reviews, and quantitative and qualitative approaches focusing on pregnant women undergoing water immersion at any stage of the labor process. RESULTS: Eleven articles were selected: two systematic reviews (one quantitative and one qualitative), five cohort studies, one case-control study, one cross-sectional observational study, and two qualitative studies. A thorough assessment of the methodology was performed using several specific tools: the Cochrane RoB 2 (Risk of Bias 2) tool for systematic reviews, JBI Critical Appraisal Checklist for Qualitative Research for qualitative studies, STROBE for observational descriptive studies, and CASPe for qualitative studies. The results provided fundamental insights that will contribute to conceptual standardization regarding the effects of water birth on maternal and fetal health. Additionally, a synthesis of the results was performed concerning types of delivery, analgesia use, pain perception, and maternal satisfaction with the water birth experience. CONCLUSIONS: In this study, we conclude that the results regarding delivery types, labor durations, and analgesia use found in the literature, along with statistically significant maternal/fetal effects, are crucial for making recommendations regarding the use of water during labor in any of its stages if the woman desires it safely.

Impact of endogenous analgesia triggered by acupuncture, stress, or noxious stimulation on REM sleep-deprived rats.

Poor sleep increases pain, at least in part, by disrupting endogenous pain modulation. However, the efficacy of endogenous analgesia in sleep-deprived subjects has never been tested. To assess this issue, we chose three different ways of triggering endogenous analgesia: (1) acupuncture, (2) acute stress, and (3) noxious stimulation, and compared their ability to decrease the pronociceptive effect induced by REM-SD (Rapid Eye Movement Sleep Deprivation) with that to decrease inflammatory hyperalgesia in the classical carrageenan model. First, we tested the ability of REM-SD to worsen carrageenan-induced hyperalgesia: A low dose of carrageenan (30 µg) in sleep-deprived Wistar rats resulted in a potentiated hyperalgesic effect that was more intense and longer-lasting than that induced by a higher standard dose of carrageenan (100 µg) or by REM-SD alone. Then, we found that (1) acupuncture, performed at ST36, completely reversed the pronociceptive effect induced by REM-SD or by carrageenan; (2) immobilization stress completely reversed the pronociceptive effect of REM-SD, while transiently inhibited carrageenan-induced hyperalgesia; (3) noxious stimulation of the forepaw by capsaicin also reversed the pronociceptive effect of REM-SD and persistently increased the nociceptive threshold above the baseline in carrageenan-treated animals. Therefore, acupuncture, stress, or noxious stimulation reversed the pronociceptive effect of REM-SD, while each intervention affected carrageenan-induced hyperalgesia differently. This study has shown that while sleep loss may disrupt endogenous pain modulation mechanisms, it does not prevent the activation of these mechanisms to induce analgesia in sleep-deprived individuals.

Beyond traditional therapies: a network meta-analysis on the treatment efficacy for chronic phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear. OBJECTIVE: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP. EVIDENCE REVIEW: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events. FINDINGS: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low). CONCLUSIONS: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs. PROSPERO REGISTRATION NUMBER: CRD42023455949.

An integrated strategy for the discovery of quality marker of Dactylicapnos scandens based on phytochemical analysis, network pharmacology and activity screening.

Dactylicapnos scandens (D. scandens) is an ethnic medicine commonly used for the treatment of analgesia. In this study, an integrated strategy was proposed for the quality evaluation of D. scandens based on "phytochemistry-network pharmacology-effectiveness-specificity" to discover and determine the quality marker (Q-marker) related to analgesia. First, phytochemical analysis was conducted using UPLC-Q-TOF-MS/MS and a self-built compound library, and 19 components were identified in D. scandens extracts. Next, the "compounds-targets" network was constructed to predict the relevant targets and compounds related to analgesia. Then, the analgesic activity of related compounds was verified through dynamic mass redistribution (DMR) assays on D2 and Mu receptors, and 5 components showed D2 antagonistic activity with IC50 values of 39.2 ± 14.7 µM, 5.46 ± 0.37 µM, 17.5 ± 1.61 µM, 7.89 ± 0.79 µM and 3.29 ± 0.73 µM, respectively. Subsequently, nine ingredients were selected as Q-markers in consideration of specificity, effectiveness and measurability, and their content was measured in 12 batches of D. scandens. Furthermore, the hierarchical cluster analysis and heatmap results indicated that the selected Q-marker could be used to discriminate D. scandens and that the content of Q-marker varied greatly in different batches. Our study shows that this strategy provides a useful method to discover the potential Q-markers of traditional Chinese medicine and offers a practical workflow for exploring the quality consistency of medicinal materials.

Effect of ABT-639 on Cav3.2 channel activity and its analgesic actions in mouse models of inflammatory and neuropathic pain.

Cav3.2 T-type calcium channels are important targets for pain relief in rodent models of inflammatory and neuropathic pain. Even though many T-type channel blockers have been tested in mice, only one molecule, ABT-639, has been tested in phase II clinical studies and did not produce analgesic effects over placebo. Here we examined the effects of ABT-639 on Cav3.2 channel activity in tsA-201 cells and dorsal root ganglion (DRG) neurons, in comparison with another established Cav3.2 inhibitor Z944. These experiments revealed that Z944 mediated ∼100-fold more potent inhibition of Cav3.2 currents than ABT-639, with the latter blocking channel activity by less than 15 percent when applied at a concentration of 30 µM. A slight increase in ABT-639 potency was observed at more depolarized holding potentials, suggesting that this compound may act preferentially on inactivated channels. We tested the effects of both compounds in the Complete Freund's Adjuvant (CFA) model of chronic inflammatory pain, and in partial sciatic nerve injury model of neuropathic pain in mice. In the neuropathic pain model, both Z944 and ABT-639 reversed mechanical hypersensitivity to similar degrees when delivered systemically, but remarkably, when delivered intrathecally, only Z944 was effective. In the CFA model, both compounds reversed thermal hyperalgesia upon systemic delivery, but only Z944 mediated pain relief upon intrathecal delivery, indicating that ABT-639 acts primarily at peripheral sites. ABT-639 lost its analgesic effects in CFA treated Cav3.2 null mice, indicating that these channels are essential for ABT-639-mediated pain relief despite its poor inhibition of Cav3.2 currents.