Search Results (22)

Background: Mas-related G-protein-coupled receptor b4 (Mrgprb4)-lineage neurons in the peripheral nervous system are a type of C fibers in hairy skin. Our prior work demonstrated that these neurons respond to both noxious and innocuous mechanical and thermal stimuli. Ablating them eliminates the pleasant sensation elicited by gentle pressure on a mouse’s nape. However, their potential role in mitigating pain and pain-related negative emotions in response to somatic stimuli remains unclear. Methods: A CFA-induced chronic pain and anxiety comorbidity model was established in C57BL/6J mice. In vivo calcium imaging of dorsal root ganglia (DRG) neurons in Mrgprb4-GCaMP6s transgenic mice characterized neuronal responses to transcutaneous electrical nerve stimulation (TENS) at the Zusanli (ST36) acupoint. Optogenetic activation (Mrgprb4-ChR2 mice) and viral ablation of Mrgprb4-lineage neurons were employed to evaluate their role in mediating TENS effects on mechanical pain thresholds and anxiety-like behaviors. Results: In vivo calcium imaging revealed that 0.5 mA TENS preferentially activated Mrgprb4-lineage neurons compared to 2.0 mA TENS. In CFA model mice, 0.5 mA TENS at ST36 significantly increased mechanical pain thresholds and reduced anxiety-like behaviors in the open-field test. Optogenetic activation of Mrgprb4-lineage neurons at ST36 replicated these analgesic and anxiolytic effects, demonstrating the sufficiency of these neurons for therapeutic outcomes. Conversely, viral ablation of L3–L5 Mrgprb4-lineage neurons substantially attenuated the therapeutic effects of 0.5 mA TENS for both pain relief and anxiety reduction, indicating their necessity in mediating TENS efficacy. Conclusions: Mrgprb4-lineage neurons serve as critical peripheral mediators of TENS-induced analgesia and anxiolysis. These findings identify a specific neuronal population underlying the therapeutic effects of somatic stimulation at ST36, providing mechanistic insights that may guide optimization of TENS parameters for treating chronic pain and comorbid anxiety in clinical settings. Full article

Background: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with limited treatment efficacy. Alternating current electroacupuncture (AC-EA) represents a novel neuromodulatory approach, though its mechanisms—particularly its influence on the gut–brain axis—remain underexplored. Methods: We investigated the neurobehavioral and microbiological effects of AC-EA in a rat model of PTSD induced by single prolonged stress. Animals received AC-EA at Baihui (GV20) and Mingmen (GV4) acupoints with varying parameters (0.5 mA/20 Hz, 1 mA/20 Hz, and 1 mA/2 Hz). Behavioral tests (open field test, elevated plus maze), histopathological assessments, immunofluorescence for TLR4, and 16S rRNA sequencing of gut microbiota were performed. Results: AC-EA at 1 mA/2 Hz significantly improved exploratory behavior and reduced anxiety-like responses (p < 0.05). This regimen also restored neuronal integrity in the hippocampus and cortex and reversed PTSD-induced gut dysbiosis, enriching beneficial genera such as Ligilactobacillus. Furthermore, AC-EA downregulated hepatic TLR4 expression, indicating suppression of neuroinflammatory signaling. Conclusions: Our findings demonstrate that AC-EA exerts neuromodulatory and microbiota-rebalancing effects via the gut–brain axis, highlighting its potential as a non-invasive therapeutic strategy for PTSD and related brain health disorders. Full article

Background/Objectives: Obstetric patients undergoing elective cesarean section (CS) with combined spinal–epidural (CSE) anesthesia often experience intraoperative nausea and vomiting (N&V). While prophylactic treatment with antiemetic drugs can be effective, it may also carry potential adverse effects for both the mother and the baby. To address this, we designed a randomized clinical trial to assess the effectiveness of transdermal scopolamine patches and electrical P6 stimulation as preventive measures for N&V in patients scheduled for elective CS under CSE anesthesia. Methods: Following the Institutional Review Board approval and informed consent, a total of 240 patients were randomly allocated into three groups: (1) transdermal scopolamine, (2) P6 stimulation (via a peripheral nerve stimulator), and (3) combined transdermal scopolamine and P6 stimulation, with 80 parturients in each group. The primary outcome was defined as the presence or absence of intraoperative nausea and vomiting during the procedure. Results: The incidences of intraoperative nausea and vomiting were similar across all three treatment groups, with no significant differences observed at any point during the surgery. Additionally, there were no notable differences in overall satisfaction with anesthetic care among the three study groups. Conclusions: These findings indicate that while both transcutaneous P6 acupoint stimulation and transdermal scopolamine are straightforward, safe, and effective methods, combining these two antiemetic strategies does not offer additional benefits in reducing nausea and vomiting. Nevertheless, both approaches may be particularly appealing to patients and obstetric anesthesiologists who prioritize treatments with fewer potential side effects. Full article

The TRPM8 channel, a temperature-sensitive ion channel, plays a crucial role in various physiological processes, particularly in the modulation of inflammation and nociception. Although electroacupuncture (EA) is a recognized analgesic treatment for pain conditions, its interaction with TRPM8 remains underexplored. This study aims to determine TRPM8′s role in EA-induced analgesia using a murine model of inflammatory pain. Mechanical allodynia, evidenced by a reduced paw withdrawal threshold (PWT), was induced in both wild-type and Trpm8^−/− mice through CFA injection. EA applied at the GB34 and LR3 acupoints significantly alleviated mechanical allodynia in both groups. In wild-type mice, the analgesic effects of EA were partially reversed by naloxone (an opioid receptor antagonist) or AM251 (a CB1 receptor antagonist) and fully reversed by their combination. In contrast, only AM251 reversed EA-induced analgesia in Trpm8^−/− or TRPM8-inhibited wild-type mice (via AMTB treatment, a TRPM8 antagonist), indicating no involvement of the opioid pathway. Additionally, the combination of menthol, a partial TRPM8 agonist, and EA enhanced analgesia in wild-type mice. In Trpm8^−/− or AMTB-pretreated mice, the CB1 receptor agonist WIN 55,212-2 (WIN) exhibited stronger analgesic effects compared to wild-type controls. These findings suggest that EA at LR3 and GB34 mediates analgesia through both opioid and endocannabinoid pathways. TRPM8 is critical for EA to activate the opioid pathway, while its inhibition or deletion shifts the analgesic mechanism towards reliance on the cannabinoid system. Understanding this mechanistic shift may help optimize EA treatment strategies and improve pain management outcomes. Full article

The analgesic efficacy of acupuncture has been widely recognized. However, the mechanism by which manual acupuncture-generated mechanical stimuli translate into biological signals remains unclear. This study employed a CFA-induced inflammatory pain rat model. Acupuncture intervention was then performed following standardized procedures. Enzyme-linked immunosorbent assay (ELISA) assessed inflammatory cytokines levels, while immunofluorescence and qRT-PCR screened the level of p38 and F-actin expression in the ST36 acupoint area of rats. Results indicated increased inflammatory factors, including IL-1β and TNFα, with reduced paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) in CFA rats compared to unmodeled rats. After acupuncture intervention, the heightened expression level of F-actin and p38 mRNA and the phosphorylation of p38 in the acupoint area was observed alongside decreased inflammatory factors in diseased ankle joints. The application of lifting and thrusting manipulations further enhanced the effect of acupuncture, in which the molecular expression level of muscle and connective tissue increased most significantly, indicating that these two tissues play a major role in the transformation of acupuncture stimulation. Moreover, antagonizing p38 expression hindered acupuncture efficacy, supporting the hypothesis that p38 MAPK-mediated F-actin transduces mechanical signals generated by acupuncture and related manipulation into biological signals. Full article

(1) Background: The medical practice of acupuncture involves the insertion of a specialized stainless needle into a specific body point, often called an acupoint, to initiate a perceived phenomenon of de-qi sensation. Therefore, the term “de-qi” describes bodily sensations experienced by the recipient during acupuncture, which may include feelings of soreness, heaviness, fullness, numbness, and migration. However, while acupuncture treatments reportedly result in acupoint activation and an increased release of neurotransmitters or cytokines, detecting these substances released into the acupoint microenvironment is often missed or delayed in clinical and basic practice. (2) Methods: To address this situation, we employed a paper-based enzyme-linked immunosorbent assay method to examine acupoint environmental changes using minute volumes of easily accessible acupoint fluids. (3) Results: Our results indicated that while levels of adenosine triphosphate (ATP), interleukin-1β, interleukin-6, glutamate, substance P, and histamine were all increased in the experimental group following electroacupuncture (EA) treatment, contrary results were observed in the sham EA and transient receptor potential vanilloid 1 (Trpv1^−/−) groups. Subsequently, TRPV1 and its associated molecules were augmented in mouse dorsal root ganglion, spinal cord, thalamus, and the somatosensory cortex, then examined by Western blotting and immunofluorescence techniques. Investigations revealed that these elevations were still unobserved in the sham EA or EA in the Trpv1^−/− groups. Furthermore, results showed that while administering ATP could mimic EA function, it could be reversed by the ATP P2 receptor antagonist, suramin. (4) Conclusions: Our data provide novel information, indicating that changes in neurotransmitter and cytokine levels can offer insight into acupuncture mechanisms and clinical targeting. Full article

Mast cells are widely distributed in various parts of the human body and play a vital role in the progression of many diseases. Recently, the close relationship between mast cells and acupoints was elucidated, and the role of mast cells in acupuncture analgesia has attracted the attention of researchers worldwide. Using mast cells, acupuncture analgesia and acupoint as key words to search CNKI, PubMed, Web of Science and other databases, combining the representative articles in these databases with the published research papers of our group, we summarized: The enrichment of mast cells and the dense arrangement of collagen fibers, microvessels, and nerves form the basis for acupoints as the reaction sites of acupuncture; acupuncture can cause the deformation of collagen fibers and activate TRPV channels on mast cells membrane, so as to stimulate mast cells to release bioactive substances and activate nerve receptors to generate analgesic effect; system biology models are set up to explain the quantitative process of information initiation and transmission at acupuncture points, and indicate that the acupuncture effect depends on the local mast cells density. In a conclusion, this review will give a scientific explanation of acupuncture analgesia from the material basis of acupoints, the local initiation, and afferent biological mechanism. Full article

Extracorporeal shockwave therapy (ESWT) has been recommended for managing pain in patients with knee osteoarthritis (KOA). The difference in therapeutic effects between radial shockwave characteristics (RaSW) and focused shockwave characteristics (FoSW) with different energy levels for KOA remains controversial. The purpose of this network meta-analysis (NMA) was to identify the effects relative to the different ESWT regime and combination treatments on pain and functional outcomes in individuals with KOA. The randomized controlled trials (RCTs) which investigated the efficacy of RaSW, FoSW, and combination treatments in patients with KOA were identified by searches of electronic databases. The included RCTs were analyzed through NMA and risk-of-bias assessment. We analyzed 69 RCTs with a total of 21 treatment arms in the NMA. Medium-energy FoSW plus physical therapy, medium-energy acupoint RaSW plus Chinese medicine, and high-energy FoSW alone were the most effective treatments for reducing pain [standard mean difference (SMD) = −4.51], restoring function (SMD = 4.97), and decreasing joint inflammation (SMD = −5.01). Population area and study quality influenced the treatment outcomes, particularly pain. Our findings indicate that medium-energy ESWT combined with physical therapy or Chinese medicine is beneficial for treating pain and increasing function in adults with KOA. Full article

Acupuncture affects the central nervous system via the regulation of neurotransmitter transmission. We previously showed that Shemen (HT7) acupoint stimulation decreased cocaine-induced dopamine release in the nucleus accumbens. Here, we used the intracranial self-stimulation (ICSS) paradigm to evaluate whether HT stimulation regulates the brain reward function of rats. We found that HT stimulation triggered a rightward shift of the frequency–rate curve and elevated the ICSS thresholds. However, HT7 stimulation did not affect the threshold-lowering effects produced by cocaine. These results indicate that HT7 points only effectively regulates the ICSS thresholds of the medial forebrain bundle in drug-naïve rats. Full article

(1) Background: Acupuncture (AP) is a safe and effective analgesic therapy. Understanding how fine needles trigger biological signals can help us optimize needling manipulation to improve its efficiency. Adenosine accumulation in treated acupoints is a vital related event. Here, we hypothesized that extracellular ATP (eATP) mobilization preceded adenosine accumulation, which involved local activation of mechanosensitive channels, especially TRPV4 protein. (2) Methods: AP was applied at the injured-side Zusanli acupoint (ST36) of acute ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in microdialysate from the acupoints was determined by luminescence assay. (3) Results: AP analgesic effect was significantly suppressed by pre-injection of GdCl₃ or ruthenium red in ST36, the wide-spectrum inhibitors of mechanosensitive channels, or by HC067047, a specific antagonist of TRPV4 channels. Microdialysate determination revealed a needling-induced transient eATP accumulation that was significantly decreased by pre-injection of HC067047. Additionally, preventing eATP hydrolysis by pre-injection of ARL67156, a non-specific inhibitor of ecto-ATPases, led to the increase in eATP levels and the abolishment of AP analgesic effect. (4) Conclusions: These observations indicate that needling-induced transient accumulation of eATP, due to the activation of mechanosensitive TRPV4 channels and the activities of ecto-ATPases, is involved in the trigger mechanism of AP analgesia. Full article

Inability to use the affected upper extremity (UE) in daily activities is a common complaint in stroke patients. The somatosensory system (central and peripheral) is essential for brain reorganization and plasticity. Neuromuscular electrical stimulation is considered an effective modality for improving UE function in stroke patients. The aim of the current study was to determine the therapeutic effects of transcutaneous electrical nerve stimulation (TENS) acupoints on cortical activity and the motor function of the affected UE in chronic stroke patients. Forty male and female patients diagnosed with stroke agreed to join the study. They were randomly assigned to group 1 (G1) and group 2 (G2). G1 received task-specific training (TST) and sham electrical stimulation while G2 received TST in addition to TENS acupoints. Session duration was 80 min. Both groups received 18 sessions for 6 successive weeks, 3 sessions per week. Evaluation was carried out before and after completion of the treatment program. Outcome measures used were the Fugl-Meyer Assessment of the upper extremity (FMA-UE) and the box and block test (BBT) as measures of the motor function of the affected UE. Brain activity of the motor area (C3) in the ipsilesional hemisphere was measured using a quantitative electroencephalogram (QEEG). The measured parameter was peak frequency. It was noted that the motor function of the affected UE improved significantly post-treatment in both groups, while no significant change was reported in the FMA-UE and BBT scores post-treatment in either G1 or G2. On the other hand, the activity of the motor area C3 improved significantly in G2 only, post-treatment, while G1 showed no significant improvement. There was also significant improvement in the activity of the motor area (C3) in G2 compared to G1 post-treatment. The results of the current study indicate that TST only or combined with TENS acupoints can be considered an effective method for improving motor function of the affected UE in chronic stroke patients, both being equally effective. However, TST combined with TENS acupoints proved better in improving brain plasticity in chronic stroke patients. Full article

Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1^−/− mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves’s tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies. Full article

Vincristine is a vinca alkaloid anti-mitotic drug with a broad spectrum of effects on solid and hematologic cancers. The major dose-limiting factor of this anti-cancer regimen is painful peripheral neuropathy. However, no gold-standard analgesic option has been used clinically. In this study, we investigated the effects and mechanism of bee venom acupuncture (BVA) to alleviate peripheral neuropathic pain induced by repeated intraperitoneal infusions of vincristine (1 mg/kg/day, days 1–5 and 8–12) in rats. Subcutaneous injection with bee venom (BV, 1.0 mg/kg) at the ST36 acupoint ameliorated cold and mechanical hypersensitivity (i.e., aberrant withdrawal responses in acetone drop and von Frey hair tests, respectively). In vivo extracellular recording demonstrated that BVA inhibited cutaneous cold (acetone) and mechanical (brush, press, and pinch) stimuli-elicited abnormal hyperexcitation of the spinal wide dynamic range (WDR) neurons in vincristine-treated rats. In addition, the microinjection of lidocaine into the ipsilateral locus coeruleus or the antagonism of the spinal α₂-adrenergic receptors clearly reversed the effects of BVA on cold and mechanical hypersensitivity, indicating a vital role of the descending noradrenergic modulation in analgesia. These findings suggest that BVA could be a potential therapeutic option for vincristine-induced peripheral neuropathy. Full article

The specificity of acupoint indication (i.e., reverse inference—diseases for which an acupoint could be used) might differ from the specificity of acupoint selection (i.e., forward inference—acupoints used for a disease). In this study, we explore acupoint specificity through reverse inferences from the dataset of prescribed acupoints for a certain disease in clinical trials. We searched acupuncture treatment regimens in randomized controlled trials included in the Cochrane Database of Systematic Reviews. For forward inference, the acupoints prescribed for each disease were quantified. For reverse inference, diseases for each acupoint were quantified. Data were normalized using Z-scores. Bayes factor correction was performed to adjust for the prior probability of diseases. The specificities of acupoint selections in 30 diseases were determined using forward inference. The specificities of acupoint indications regarding 49 acupoints were identified using reverse inference and then subjected to Bayes factor correction. Two types of acupoint indications were identified for 24 acupoints: regional and distal. Our approach suggests that the specificity of acupoint indication can be inferred from clinical data using reverse inference. Acupoint indication will improve our understanding of acupoint specificity and will lead to the establishment of a new model of analysis and educational resources for acupoint characteristics. Full article

Inflammatory pain sensation is an important symptom which protects the body against additional tissue damage and promotes healing. Discovering long-term and effective treatments for pain remains crucial in providing efficient healthcare. Electroacupuncture (EA) is a successful therapy used for pain relief. We aimed to investigate effects and mechanisms of Complete Freund’s Adjuvant (CFA)-inducing inflammatory pain in the cerebellum, and the inhibition of this inflammatory hyperalgesia using EA at Zusanli acupoint (ST36). The results display a significant increase in mechanical and thermal sensitivities in the CFA and CFA + SHAM groups, which was significantly reduced in the CFA+EA and CFA + KO groups. This evidence was substantiated in the protein levels observed using immunoblotting, and presented with significant escalations after CFA inducing inflammatory hyperalgesia in CFA and CFA + SHAM groups. Then, they were significantly attenuated by EA in the CFA + EA group. Furthermore, the CFA + transient receptor vanilloid member 1 (TRPV1)^−/− group indicated similar significant decreases of protein expression. Additionally, a concomitant overexpression in lobule VIa was also observed in immunofluorescence. These consequences suggest that CFA-induced inflammatory pain provokes modifications in cerebellum lobules V, VIa and VII, which can subsequently be regulated by EA treatment at the ST36 through its action on TRPV1 and related molecular pathways. Full article